PROTEIN BIOMARKERS AND THERAPEUTIC TARGETS FOR OSTEOARTHRITIS

BACKGROUND

Musculoskeletal conditions affect hundreds of millions of people around the world and this figure is expected to increase sharply due to the predicted doubling of the population over 50 by the year 2020 (“The Global Burden of Disease. A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020”, C. J. L. Murray and A. D. Lopez (Eds.), 1996, Harvard University Press: Cambridge, Mass.). Musculoskeletal conditions give rise to enormous healthcare expenditures and loss of economic productivity, and therefore have a huge impact on society. In the U.S. alone, musculoskeletal conditions were estimated to have cost $214 billion in 1995 (A. Praemer et al., “Musculoskeletal Conditions in the United States”, 2nd Ed., 1999, American Academy of Orthopaedic Surgeons Rosemont, Ill.). While there are many types of musculoskeletal conditions, osteoarthritis is one of the most common chronic musculoskeletal disorders encountered by physicians throughout the world.

Osteoarthritis (OA) is a non-inflammatory joint disease, which is characterized by the breakdown of joint cartilage. It may affect one or more joints in the body, including those of the fingers, neck, shoulder, hips, knees, lower spine region, and feet. OA can cause pain and severely impair mobility and lower extremity function (E. Bagge et al., Age Ageing, 1992, 21: 160-167; D. Hamerman, Ann. Rheum. Dis., 1995, 54: 82-85; J. Jordan et al., J. Rheumatol., 1997, 24: 1344-1349; S. M. Ling and J. M. Bathon, J. Am. Geriatr. Soc., 1998, 46: 216-225), which can lead to disability and difficulty maintaining independence (A. A. Guccione et al., Am. J. Public Health, 1994, 84: 351-358; M. A Gignac et al., J. Gerontol. B: Psychol. Sci. Soc. Sci., 2000, 55: 362-372; M. C. Corti and C. Rignon, Aging Clin. Exp. Res., 2003, 15: 359-363).

Currently, diagnosis of OA is typically based upon radiological examination as well as clinical observations including localized tenderness, use-related pain, bony or soft tissue swelling, joint instability, limited joint function, muscle spasm, and crepitus (i.e., cracking or grinding sensation). While the diagnosis of OA is often suggested on physical examination, radiographic evaluation is generally used to confirm the diagnosis or assess the severity of the disease. The radiographic hallmarks of OA include nonuniform joint space loss, osteophyte formation, cyst formation, and subchondral sclerosis. While these characteristic features are generally present in X-ray images of “severe” or “late” OA, patients with “early” OA may not show radiographic evidence of bony changes, joint space narrowing and/or osteophytosis, making the diagnosis unclear or difficult to establish.

SUMMARY OF THE INVENTION

The present invention relates to the use of protein expression profiles with clinical relevance to osteoarthritis. In particular, the invention provides the identity of proteins, whose expression is correlated with osteoarthritis (OA) and/or with different phases of advancement of the disease. These protein expression profiles may be applied to the diagnosis and staging of disease useful for prognostic purposes in OA. Compared to existing methods of diagnosis, the protein expression profiles disclosed herein constitute a more robust signature of OA and OA progression, and provide a more reliable basis for the selection of appropriate therapeutic regimens. The invention also relates to the screening of drugs that target these biomarkers, in particular for the development of new therapeutics for the treatment of OA.

In general, the invention involves the use of expression profiles of the marker proteins listed in attached Tables 1-6 for diagnosing osteoarthritis. More specifically, the present invention provides methods for distinguishing between stages of osteoarthritis. Methods are provided that comprise steps of: providing a biological sample obtained from a subject to be tested; determining, in the biological sample, the level of expression of a one or more of polypeptides selected from the group consisting of proteins presented in Tables 1-6.

In one embodiment, the proteins can comprise at least one of alpha-2-macroglobulin precursor, fibronectin precursor, Chain B structure of complement C3b, C9 complement protein, coagulation factor II precursor, alpha-1-antichymotrypsin, complement component C3, complement factor H, inter-alpha-trypsin heavy chain H1 precursor, complement factor H isoform a precursor, gelsolin isoform a precursor, ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor, phosphatidylinositol-glycan-specific phospholipase D1 precursor, inter-alpha-trypsin inhibitor family heavy chain-related protein, glycosylphosphatidylinositol specific phosphatase D1, complement component C6 precursor peptide, complement factor B, pre-pro-alpha(I) collagen, SERPIN2 protein, gp-180-carboxypeptidase D-like enzyme, Fibulin-1 isoform D precursor, plasminogen, HGF activator preproprotein, afamin precursor, Vitamin K-dependent protein, complement component 1 s subcomponent, inter-alpha-trypsin inhibitor, ASPIC, complement component 3 precursor, plasma kallikrein precursor, annexin A2 isoform 2, glucosamine(N-acetyl)-6-sulfatase precursor, (cystic fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding protein A9, coagulation factor XIII A chain precursor, peptidoglycan recognition protein L precursor, complement component 4 binding protein, inter-alpha-trypsin inhibitor heavy chain H1 precursor, fibrinogen gamma chain, Ig mu chain precursor, phospholipase D3 isoform, moesin, alpha-2-antiplasmin precursor, kininogen, thrombin inhibitor, Chain A antithrombin III, L-plastin, complement component 1, alpha-1-B-glycoprotein, hemopexin precursor, complement component C4A, apolipoprotein A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin peptidase inhibitor clade I, follistatin-like 1 precursor, complement factor H-related protein 1 precursor, Chain A Crystal Structure of Lipid-Free human Apolipoprotein A-1, phospholipase D3 isoform 2, Chain E Structure of human transferring receptor-transferrin complex, complement component C3, analogs and fragments thereof; and any combination thereof.

In still other embodiments, the proteins can comprise at least one of fibronectin precursor, complement component C3, alpha-2-macroglobulin precursor, Chain B Structure of Complement C3b, complement factor H, fibronectin 1 isoform 3 preproprotein, alpha-2-macroglobulin, collagen type IV alpha 1, alph 2 type IV collagen preprotein, inter-alpha-trypsin inhibitor, C-terminal inter-alpha trypsin inhibitor, ceruloplasmin, phosphatidylinositol-glycan-specific phospholipase D1, afamin precursor, complement component 6 isoform CRA_b, inter-alpha-trypsin inhibitor heavy chain-related protein, Chain A Crystal Structure of human Galectin-7, serum albumin, COMP, ALB protein, gelsolin isoform a precursor, complement factor B, fibulin-1 isoform D precursor, inter-alpha-globulin inhibitor H4, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, Annexin A2 isoform 2, homerin precursor, complement component 1 s subcomponent, ASPIC, Vitamin K-dependent protein, plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, coagulation factor II precursor, insulin-like growth factor binding protein acid labile subunit, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, antithrombin III, glucosamine(N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, acid labile subunit, alpha-1-B-glycoprotein, thrombin inhibitor, C9 complement protein, Coagulation factor XIII B chain precursor, hemopexin precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma chain, inter-alpha (globulin) inhibitor H1, alpha-2-antiplasmin precursor, vitronectin precursor, Vitamin K-dependent protein S precursor, complement component 9, GRP78, analogs and fragments thereof; and any combination thereof.

In further embodiments, the proteins can comprise at least one of fibronectin precursor, alpha-2-macroglobulin precursor, Chain B Structure of Complement C3b, complement factor H, fibronectin 1 isoform 3 preproprotein, collagen type IV alpha 1, alph 2 type IV collagen preprotein, inter-alpha-trypsin inhibitor, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, afamin precursor, complement component 6 isoform CRA_b, inter-alpha-trypsin inhibitor heavy chain-related protein, Chain A Crystal Structure of human Galectin-7, COMP, ALB protein, gelsolin isoform a precursor, complement factor B, fibulin-1 isoform D precursor, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, Annexin A2 isoform 2, homerin precursor, complement component 1 s subcomponent, ASPIC, Vitamin K-dependent protein, plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, coagulation factor II precursor, insulin-like growth factor binding protein acid labile subunit, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, antithrombin III, glucosamine(N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, acid labile subunit, alpha-1-B-glycoprotein, thrombin inhibitor, C9 complement protein, Coagulation factor XIII B chain precursor, hemopexin precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma chain, inter-alpha (globulin) inhibitor H1, alpha-2-antiplasmin precursor, vitronectin precursor, Vitamin K-dependent protein S precursor, complement component 9, GRP78, analogs and fragments thereof; and any combination thereof.

In still other embodiments, the proteins can comprise at least one of alpha-2-macroglobulin precursor, fibronectin precursor, Chain B structure of complement C3b, C9 complement protein, coagulation factor II precursor, alpha-1-antichymotrypsin, complement component C3, complement factor H, inter-alpha-trypsin heavy chain H1 precursor, complement factor H isoform a precursor, gelsolin isoform a precursor, ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor, phosphatidylinositol-glycan-specific phospholipase D1 precursor, inter-alpha-trypsin inhibitor family heavy chain-related protein, glycosylphosphatidylinositol specific phosphatase D1, complement component C6 precursor peptide, complement factor B, pre-pro-alpha(I) collagen, SERPIN2 protein, gp-180-carboxypeptidase D-like enzyme, Fibulin-1 isoform D precursor, plasminogen, HGF activator preproprotein, afamin precursor, Vitamin K-dependent protein, complement component 1 s subcomponent, inter-alpha-trypsin inhibitor, ASPIC, complement component 3 precursor, plasma kallikrein precursor, annexin A2 isoform 2, glucosamine(N-acetyl)-6-sulfatase precursor, (cystic fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding protein A9, coagulation factor XIII A chain precursor, peptidoglycan recognition protein L precursor, complement component 4 binding protein, inter-alpha-trypsin inhibitor heavy chain H1 precursor, fibrinogen gamma chain, Ig mu chain precursor, phospholipase D3 isoform, moesin, alpha-2-antiplasmin precursor, kininogen, thrombin inhibitor, Chain A antithrombin III, L-plastin, complement component 1, alpha-1-B-glycoprotein, hemopexin precursor, complement component C4A, apolipoprotein A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin peptidase inhibitor clade I, follistatin-like 1 precursor, complement factor H-related protein 1 precursor, Chain A Crystal Structure of Lipid-Free human Apolipoprotein A-1, phospholipase D3 isoform 2, Chain E Structure of human transferring receptor-transferrin complex, complement component C3, fibronectin 1 isoform 3 preproprotein, alpha-2-macroglobulin, collagen type IV alpha 1, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, complement component 6 isoform CRA_b, Chain A Crystal Structure of human Galectin-7, serum albumin, ALB protein, inter-alpha-globulin inhibitor H4, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, homerin precursor, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, insulin-like growth factor binding protein acid labile, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, alpha-1-B-glycoprotein, Coagulation factor XIII B chain precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, inter-alpha (globulin) inhibitor H1, vitronectin precursor, Vitamin K-dependent protein S precursor, GRP78, analogs and fragments thereof; and any combination thereof.

In other embodiments, the proteins can comprise at least one of alpha-2-macroglobulin precursor, fibronectin precursor, Chain B structure of complement C3b, C9 complement protein, coagulation factor II precursor, alpha-1-antichymotrypsin, complement factor H, inter-alpha-trypsin heavy chain H1 precursor, complement factor H isoform a precursor, gelsolin isoform a precursor, inter-alpha-trypsin inhibitor heavy chain H4 precursor, phosphatidylinositol-glycan-specific phospholipase D1 precursor, inter-alpha-trypsin inhibitor family heavy chain-related protein, glycosylphosphatidylinositol specific phosphatase D1, complement component C6 precursor peptide, complement factor B, pre-pro-alpha(I) collagen, SERPIN2 protein, gp-180-carboxypeptidase D-like enzyme, Fibulin-1 isoform D precursor, plasminogen, HGF activator preproprotein, afamin precursor, Vitamin K-dependent protein, complement component 1 s subcomponent, inter-alpha-trypsin inhibitor, ASPIC, complement component 3 precursor, plasma kallikrein precursor, annexin A2 isoform 2, glucosamine(N-acetyl)-6-sulfatase precursor, (cystic fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), 5100 Calcium binding protein A9, coagulation factor XIII A chain precursor, peptidoglycan recognition protein L precursor, complement component 4 binding protein, inter-alpha-trypsin inhibitor heavy chain H1 precursor, fibrinogen gamma chain, Ig mu chain precursor, phospholipase D3 isoform, moesin, alpha-2-antiplasmin precursor, kininogen, thrombin inhibitor, Chain A antithrombin III, L-plastin, complement component 1, alpha-1-B-glycoprotein, hemopexin precursor, complement component C4A, apolipoprotein A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin peptidase inhibitor clade I, follistatin-like 1 precursor, complement factor H-related protein 1 precursor, Chain A Crystal Structure of Lipid-Free human Apolipoprotein A-1, phospholipase D3 isoform 2, Chain E Structure of human transferring receptor-transferrin complex, complement component C3, fibronectin 1 isoform 3 preproprotein, collagen type IV alpha 1, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, complement component 6 isoform CRA_b, Chain A Crystal Structure of human Galectin-7, ALB protein, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, homerin precursor, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, insulin-like growth factor binding protein acid labile, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, alpha-1-B-glycoprotein, Coagulation factor XIII B chain precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, inter-alpha (globulin) inhibitor H1, vitronectin precursor, Vitamin K-dependent protein S precursor, GRP78, analogs and fragments thereof; and any combination thereof.

In certain embodiments, providing an osteoarthritis diagnosis to the subject comprises comparing the test protein expression profile to a control protein expression, wherein the difference between the test protein expression profile and the control protein expression profile is indicative of early or late stage osteoarthritis in the subject; and based on the comparison, identifying osteoarthritis in the subject as early stage or late stage osteoarthritis.

In certain embodiments, the control protein expression profile is an early stage osteoarthritis expression profile, and the difference is indicative of late stage osteoarthritis. In such embodiments, the difference may be selected from the group consisting of an increase or decrease in the level of expression of one or more proteins selected from the group consisting of alpha-2-macroglobulin precursor, fibronectin precursor, Chain B structure of complement C3b, C9 complement protein, coagulation factor II precursor, alpha-1-antichymotrypsin, complement factor H, inter-alpha-trypsin heavy chain H1 precursor, complement factor H isoform a precursor, gelsolin isoform a precursor, inter-alpha-trypsin inhibitor heavy chain H4 precursor, phosphatidylinositol-glycan-specific phospholipase D1 precursor, inter-alpha-trypsin inhibitor family heavy chain-related protein, glycosylphosphatidylinositol specific phosphatase D1, complement component C6 precursor peptide, complement factor B, pre-pro-alpha(I) collagen, SERPIN2 protein, gp-180-carboxypeptidase D-like enzyme, Fibulin-1 isoform D precursor, plasminogen, HGF activator preproprotein, afamin precursor, Vitamin K-dependent protein, complement component 1 s subcomponent, inter-alpha-trypsin inhibitor, ASPIC, complement component 3 precursor, plasma kallikrein precursor, annexin A2 isoform 2, glucosamine(N-acetyl)-6-sulfatase precursor, (cystic fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding protein A9, coagulation factor XIII A chain precursor, peptidoglycan recognition protein L precursor, complement component 4 binding protein, inter-alpha-trypsin inhibitor heavy chain H1 precursor, fibrinogen gamma chain, Ig mu chain precursor, phospholipase D3 isoform, moesin, alpha-2-antiplasmin precursor, kininogen, thrombin inhibitor, Chain A antithrombin III, L-plastin, complement component 1, alpha-1-B-glycoprotein, hemopexin precursor, complement component C4A, apolipoprotein A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin peptidase inhibitor clade I, follistatin-like 1 precursor, complement factor H-related protein 1 precursor, Chain A Crystal Structure of Lipid-Free human Apolipoprotein A-1, phospholipase D3 isoform 2, Chain E Structure of human transferring receptor-transferrin complex, complement component C3, analogs and fragments thereof; and any combination thereof.

In other embodiments, the control protein expression profile is a late stage osteoarthritis expression profile, and the difference is indicative of early stage osteoarthritis. In such embodiments, the difference may be selected from the group consisting of an increase or decrease in the level of expression of one or more proteins selected from the group consisting of alpha-2-macroglobulin precursor, fibronectin precursor, Chain B structure of complement C3b, C9 complement protein, coagulation factor II precursor, alpha-1-antichymotrypsin, complement factor H, inter-alpha-trypsin heavy chain H1 precursor, complement factor H isoform a precursor, gelsolin isoform a precursor, inter-alpha-trypsin inhibitor heavy chain H4 precursor, phosphatidylinositol-glycan-specific phospholipase D1 precursor, inter-alpha-trypsin inhibitor family heavy chain-related protein, glycosylphosphatidylinositol specific phosphatase D1, complement component C6 precursor peptide, complement factor B, pre-pro-alpha(I) collagen, SERPIN2 protein, gp-180-carboxypeptidase D-like enzyme, Fibulin-1 isoform D precursor, plasminogen, HGF activator preproprotein, afamin precursor, Vitamin K-dependent protein, complement component 1 s subcomponent, inter-alpha-trypsin inhibitor, ASPIC, complement component 3 precursor, plasma kallikrein precursor, annexin A2 isoform 2, glucosamine(N-acetyl)-6-sulfatase precursor, (cystic fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding protein A9, coagulation factor XIII A chain precursor, peptidoglycan recognition protein L precursor, complement component 4 binding protein, inter-alpha-trypsin inhibitor heavy chain H1 precursor, fibrinogen gamma chain, Ig mu chain precursor, phospholipase D3 isoform, moesin, alpha-2-antiplasmin precursor, kininogen, thrombin inhibitor, Chain A antithrombin III, L-plastin, complement component 1, alpha-1-B-glycoprotein, hemopexin precursor, complement component C4A, apolipoprotein A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin peptidase inhibitor clade I, follistatin-like 1 precursor, complement factor H-related protein 1 precursor, Chain A Crystal Structure of Lipid-Free human Apolipoprotein A-1, phospholipase D3 isoform 2, Chain E Structure of human transferring receptor-transferrin complex, complement component C3, analogs and fragments thereof; and any combination thereof.

In other embodiments, the control protein expression profile is a healthy or normal expression profile, and the difference is indicative of early or late stage osteoarthritis. In such embodiments, the difference may be selected from the group consisting of an increase or decrease in the level of expression of one or more proteins selected from the group consisting of fibronectin precursor, alpha-2-macroglobulin precursor, Chain B Structure of Complement C3b, complement factor H, fibronectin 1 isoform 3 preproprotein, collagen type IV alpha 1, alph 2 type IV collagen preprotein, inter-alpha-trypsin inhibitor, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, afamin precursor, complement component 6 isoform CRA_b, inter-alpha-trypsin inhibitor heavy chain-related protein, Chain A Crystal Structure of human Galectin-7, COMP, ALB protein, gelsolin isoform a precursor, complement factor B, fibulin-1 isoform D precursor, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, Annexin A2 isoform 2, homerin precursor, complement component 1 s subcomponent, ASPIC, Vitamin K-dependent protein, plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, coagulation factor II precursor, insulin-like growth factor binding protein acid labile subunit, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, antithrombin III, glucosamine(N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, acid labile subunit, alpha-1-B-glycoprotein, thrombin inhibitor, C9 complement protein, Coagulation factor XIII B chain precursor, hemopexin precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma chain, inter-alpha (globulin) inhibitor H1, alpha-2-antiplasmin precursor, vitronectin precursor, Vitamin K-dependent protein S precursor, complement component 9, GRP78, analogs and fragments thereof; and any combination thereof.

In still other embodiments, the control protein expression profile is a late or early stage osteoarthritis expression profile, and the difference is indicative of normal or healthy subject. In such embodiments, the difference may be selected from the group consisting of an increase or decrease in the level of expression of one or more proteins selected from the group consisting of fibronectin precursor, alpha-2-macroglobulin precursor, Chain B Structure of Complement C3b, complement factor H, fibronectin 1 isoform 3 preproprotein, collagen type IV alpha 1, alph 2 type IV collagen preprotein, inter-alpha-trypsin inhibitor, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, afamin precursor, complement component 6 isoform CRA_b, inter-alpha-trypsin inhibitor heavy chain-related protein, Chain A Crystal Structure of human Galectin-7, COMP, ALB protein, gelsolin isoform a precursor, complement factor B, fibulin-1 isoform D precursor, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, Annexin A2 isoform 2, hornerin precursor, complement component 1 subcomponent, ASPIC, Vitamin K-dependent protein, plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, coagulation factor II precursor, insulin-like growth factor binding protein acid labile subunit, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, antithrombin III, glucosamine(N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, acid labile subunit, alpha-1-B-glycoprotein, thrombin inhibitor, C9 complement protein, Coagulation factor XIII B chain precursor, hemopexin precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma chain, inter-alpha (globulin) inhibitor H1, alpha-2-antiplasmin precursor, vitronectin precursor, Vitamin K-dependent protein S precursor, complement component 9, GRP78, analogs and fragments thereof; and any combination thereof.

In these methods, the biological sample can comprise a sample of blood or blood product, a sample of urine, a sample of joint fluid, a sample of saliva, or a sample of synovial fluid. In certain preferred embodiments, the biological sample comprises a sample of synovial fluid. Determination of the level of expression of one or more of polypeptides according to the present invention may comprise exposing the biological sample to at least one antibody specific for at least one of said polypeptides.

In certain embodiments, the subject is a human being, for example, a patient suspected of having osteoarthritis or a patient diagnosed with osteoarthritis but whose stage of osteoarthritis is unknown.

The inventive methods may further comprise a step of selecting a therapy for the subject based on the determination of the stage of osteoarthritis for the subject.

In yet another aspect, the present invention provides OA expression profile maps comprising expression level information for one or more of polypeptides selected from the group consisting of the proteins presented in Tables 1-6, analogs and fragments thereof. The OA expression profile may comprise expression level information for at least one biological sample obtained from a healthy individual, an individual with early stage osteoarthritis or an individual with late osteopathic osteoarthritis.

In still another aspect, the present invention provides kits for identifying the stage of osteoarthritis in a subject. Inventive kits comprise at least one reagent that specifically detects expression levels of at least one biomarker selected from the group consisting of: polypeptides selected from the group consisting of the proteins presented in Tables 1 and 3, analogs and fragments thereof, and nucleic acid molecules comprising polynucleotide sequences coding for polypeptides selected from the group consisting of the proteins presented in Tables 1 and 3, analogs and fragments thereof, and instructions for using said kits for identifying osteoarthritis in a subject as early Osteopathic or late osteoarthritic osteoarthritis.

In certain embodiments, the reagent that specifically detects expression levels of at least one biomarker comprises an antibody that specifically binds to at least one the polypeptides. In other embodiments, the reagent comprises a nucleic acid probe complementary to a polynucleotide sequence coding for at least one of the polypeptides. For example, the nucleic acid probe may be a cDNA or an oligonucleotide, and, in certain embodiments, is immobilized on a substrate surface.

Kits of the present invention may further comprise instructions required by a regulatory agency (e.g., the United States Food and Drug Administration) for use in in vitro diagnostic products; one or more of: extraction buffer/reagents and protocol, amplification buffer/reagents and protocol, hybridization buffer/reagents and protocol, immunodetection buffer/reagents and protocol, and labeling buffer/reagents and protocol, and/or at least one OA expression profile map as described above.

These and other objects, advantages and features of the present invention will become apparent to those of ordinary skill in the art having read the following detailed description of the preferred embodiments.

DETAILED DESCRIPTION

Throughout the specification, several terms are employed that are defined in the following paragraphs.

The term “subject” and “individual” are used herein interchangeably. They refer to a human or another mammal (e.g., primate, dog, cat, goat, horse, pig, mouse, rat, rabbit, and the like), that can be afflicted with osteoarthritis, but may or may not have the disease. In many embodiments, the subject is a human being.

The term “subject suspected of having osteoarthritis (OA)” refers to a subject that presents one or more symptoms indicative of OA (e.g., joint pain, localized tenderness, bony or soft tissue swelling, joint instability, crepitus) or that is being screened for OA (e.g., during a routine physical examination). A subject suspected of having OA may also have one or more risk factors (e.g., age, obesity, traumatic injury, overuse due to sports or occupational stresses, or family history). The term encompasses individuals who have not been tested for OA as well as individuals who have received an initial diagnosis (e.g., based on radiological examination) but for whom the stage of OA is not known.

The terms “osteoarthritis stage”, “osteoarthritis phase”, and “stage osteoarthritis” are used herein interchangeably and refer to the degree of advancement or progression of the disease. The present invention provides a means for determining the stage of the disease. In particular, the methods provided herein allows detection of “mild” or “early” stage OA, and of “severe” or “late” stage OA. Other staging systems known in the art include, for example, that developed by Marshall (W. Marshall, J. Rheumatol., 1996, 23: 582-584).

As used herein, the term “diagnosis” refers to a process aimed at determining if an individual is afflicted with a disease or ailment. In the context of the present invention, “diagnosis of OA” refers to a process aimed at one or more of: determining if an individual is afflicted with OA, and determining the stage of the disease (e.g., early OA or late OA).

The term “biological sample” is used herein in its broadest sense. A biological sample may be obtained from a subject (e.g., a human) or from components (e.g., tissues) of a subject. The sample may be of any biological tissue or fluid with which biomarkers of the present invention may be assayed. Frequently, the sample will be a “clinical sample”, i.e., a sample derived from a patient. Such samples include, but are not limited to, bodily fluids which may or may not contain cells, e.g., blood, urine, synovial fluid, saliva, and joint fluid; tissue or fine needle biopsy samples, such as from bone or cartilage; and archival samples with known diagnosis, treatment and/or outcome history. Biological samples may also include sections of tissues such as frozen sections taken from histological purposes. The term biological sample also encompasses any material derived by processing the biological sample. Derived materials include, but are not limited to, cells (or their progeny) isolated from the sample, proteins or nucleic acid molecules extracted from the sample. Processing of the biological sample may involve one or more of, filtration, distillation, extraction, concentration, inactivation of interfering components, addition of reagents, and the like.

The terms “normal” and “healthy” are used herein interchangeably. They refer to an individual or group of individuals who have not shown any OA symptoms, including joint pain, and have not been diagnosed with cartilage injury or OA. Preferably, said normal individual (or group of individuals) is not on medication affecting OA and has not been diagnosed with any other disease. In certain embodiments, normal individuals have similar sex, age, body mass index as compared with the individual from which the sample to be tested was obtained. The term “normal” is also used herein to qualify a sample isolated from a healthy individual.

In the context of the present invention, the term “control sample” refers to one or more biological samples isolated from an individual or group of individuals that are normal (i.e., healthy). A control sample can also refer to a biological sample isolated from a patient or group of patients diagnosed with a specific stage of OA (e.g., early OA or late OA). The term “control sample” (or “control”) can also refer to the compilation of data derived from samples of one or more individuals classified as normal, or one or more individuals diagnosed with OA, a specific stage of OA, or one or more individuals having undergone treatment of OA.

The terms “OA biomarker” and “biomarker” are used herein interchangeably. They refer to a protein selected from the set of proteins provided by the present invention and whose expression profile was found to be indicative of OA and/or a particular stage of OA. The term “biomarker” also encompasses nucleic acid molecules comprising a nucleotide sequence, which codes for a marker protein of the present invention as well as polynucleotides that hybridize with portions of these nucleic acid molecules.

As used herein, the term “indicative of OA”, when applied to a biomarker, refers to an expression pattern or profile which is diagnostic of OA or a stage of OA such that the expression pattern is found significantly more often in patients with the disease or a stage of the disease than in patients without the disease or another stage of the disease (as determined using routine statistical methods setting confidence levels at a minimum of 95%). Preferably, an expression pattern which is indicative of OA is found in at least 60% of patients who have the disease and is found in less than 10% of subjects who do not have the disease. More preferably, an expression pattern which is indicative of OA is found in at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or more in patients who have the disease and is found in less than 10%, less than 8%, less than 5%, less than 2.5%, or less than 1% of subjects who do not have the disease.

As used herein, the term “differentially expressed biomarker” refers to a biomarker whose level of expression is different in a subject (or a population of subjects) afflicted with OA relative to its level of expression in a healthy or normal subject (or a population of healthy or normal subjects). The term also encompasses a biomarker whose level of expression is different at different stages of the disease (e.g., mild or early OA, severe or late OA). Differential expression includes quantitative, as well as qualitative, differences in the temporal or cellular expression pattern of the biomarker. As described in greater details below, a differentially expressed biomarker, alone or in combination with other differentially expressed biomarkers, is useful in a variety of different applications in diagnostic, staging, therapeutic, drug development and related areas. The expression patterns of the differentially expressed biomarkers disclosed herein can be described as a fingerprint or a signature of OA, OA stage and OA progression. They can be used as a point of reference to compare and characterize unknown samples and samples for which further information is sought. The term “decreased level of expression” as used herein, refers to a decrease in expression of at least 10% or more. For example, 20%, 30%, 40%, or 50%, 60%, 70%, 80%, 90% or more, or a decrease in expression of greater than 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, 100-fold or more as measured by one or more methods described herein. The term “increased level of expression” as used herein, refers to an increase in expression of at least 10% or more. For example, 20%, 30%, 40%, or 50%, 60%, 70%, 80%, 90% or more or an increase in expression of greater than I-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, 100-fold or more as measured by one or more methods, such as method described herein.

The terms “protein”, “polypeptide”, and “peptide” are used herein interchangeably, and refer to amino acid sequences of a variety of lengths, either in their neutral (uncharged) forms or as salts, and either unmodified or modified by glycosylation, side chain oxidation, or phosphorylation. In certain embodiments, the amino acid sequence is the full-length native protein. In other embodiments, the amino acid sequence is a smaller fragment of the full-length protein. In still other embodiments, the amino acid sequence is modified by additional substituents attached to the amino acid side chains, such as glycosyl units, lipids, or inorganic ions such as phosphates, as well as modifications relating to chemical conversion of the chains, such as oxidation of sulfhydryl groups. Thus, the term “protein” (or its equivalent terms) is intended to include the amino acid sequence of the full-length native protein, subject to those modifications that do not change its specific properties. In particular, the term “protein” encompasses protein isoforms, i.e., variants that are encoded by the same gene, but that differ in their pI or MW, or both. Such isoforms can differ in their amino acid sequence (e.g., as a result of alternative splicing or limited proteolysis), or in the alternative, may arise from differential post-translational modification (e.g., glycosylation, acylation, phosphorylation).

The term “protein analog”, as used herein, refers to a polypeptide that possesses a similar or identical function as the full-length native protein but need not necessarily comprise an amino acid sequence that is similar or identical to the amino acid sequence of the protein, or possesses a structure that is similar or identical to that of the protein. Preferably, in the context of the present invention, a protein analog has an amino acid sequence that is at least 30% (more preferably, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99%) identical to the amino acid sequence of the full-length native protein.

The term “protein fragment”, as used herein, refers to a polypeptide comprising an amino acid sequence of at least 4 amino acid residues (preferably, at least 10 amino acid residues, at least 15 amino acid residues, at least 20 amino acid residues, at least 25 amino acid residues, at least 40 amino acid residues, at least 50 amino acid residues, at least 60 amino acid residues, at least 70 amino acid residues, at least 80 amino acid residues, at least 90 amino acid residues, at least 100 amino acid residues, at least 125 amino acid residues, at least 150 amino acid residues, at least 175 amino acid residues, at least 200 amino acid residues, or at least 250 amino acid residues) of the amino acid sequence of a second polypeptide. The fragment of a marker protein may or may not possess a functional activity of the full-length native protein.

The terms “nucleic acid molecule” and “polynucleotide” are used herein interchangeably. They refer to a deoxyribonucleotide or ribonucleotide polymer in either single- or double-stranded form, and unless otherwise stated, encompass known analogs of natural nucleotides that can function in a similar manner as naturally occurring nucleotides. The terms encompass nucleic acid-like structures with synthetic backbones, as well as amplification products.

As used herein, the term “a reagent that specifically detects expression levels” refers to one or more reagents used to detect the expression level of one or more biomarkers (e.g., a polypeptide selected from the marker proteins provided herein, a nucleic acid molecule comprising a polynucleotide sequence coding for a marker protein, or a polynucleotide that hybridizes with at least a portion of the nucleic acid molecule). Examples of suitable reagents include, but are not limited to, antibodies capable of specifically binding to a marker protein of interest, nucleic acid probes capable of specifically hybridizing to a polynucleotide sequence of interest, or PCR primers capable of specifically amplifying a polynucleotide sequence of interest. The term “amplify” is used herein in the broad sense to mean creating/generating an amplification product. “Amplification”, as used herein, generally refers to the process of producing multiple copies of a desired sequence, particularly those of a sample. A “copy” does not necessarily mean perfect sequence complementarity or identity to the template sequence.

The term “hybridizing” refers to the binding of two single stranded nucleic acids via complementary base pairing. The term “specific hybridization” refers to a process in which a nucleic acid molecule preferentially binds, duplexes, or hybridizes to a particular nucleic acid sequence under stringent conditions (e.g., in the presence of competitor nucleic acids with a lower degree of complementarity to the hybridizing strand). In certain embodiments of the present invention, these terms more specifically refer to a process in which a nucleic acid fragment (or segment) from a test sample preferentially binds to a particular probe and to a lesser extent or not at all, to other probes, for example, when these probes are immobilized on an array.

The terms “array”, “micro-array”, and “biochip” are used herein interchangeably. They refer to an arrangement, on a substrate surface, of hybridizable array elements, preferably, multiple nucleic acid molecules of known sequences. Each nucleic acid molecule is immobilized to a discrete spot (i.e., a defined location or assigned position) on the substrate surface. The term “micro-array” more specifically refers to an array that is miniaturized so as to require microscopic examination for visual evaluation.

The term “probe”, as used herein, refers to a nucleic acid molecule of known sequence, which can be a short DNA sequence (i.e., an oligonucleotide), a PCR product, or mRNA isolate. Probes are specific DNA sequences to which nucleic acid fragments from a test sample are hybridized. Probes specifically bind to nucleic acids of complementary or substantially complementary sequence through one or more types of chemical bonds, usually through hydrogen bond formation.

The terms “labeled”, “labeled with a detectable agent” and “labeled with a detectable moiety” are used herein interchangeably. These terms are used to specify that an entity (e.g., a probe) can be visualized, for example, following binding to another entity (e.g., a polynucleotide or polypeptide). Preferably, the detectable agent or moiety is selected such that it generates a signal which can be measured and whose intensity is related to the amount of bound entity. In array-based methods, the detectable agent or moiety is also preferably selected such that it generates a localized signal, thereby allowing spatial resolution of the signal from each spot on the array. Methods for labeling polypeptides or polynucleotides are well-known in the art. Labeled polypeptides or polynucleotides can be prepared by incorporation of or conjugation to a label, that is directly or indirectly detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, or chemical means. Suitable detectable agents include, but are not limited to, various ligands, radionuclides, fluorescent dyes, chemiluminescent agents, microparticles, enzymes, calorimetric labels, magnetic labels, and haptens. Detectable moieties can also be biological molecules such as molecular beacons and aptamer beacons.

The term “OA expression profile map” refers to a presentation of expression levels of a set of biomarkers in a particular status of OA (e.g., absence of disease, OA, early OA and late OA). The map may be presented as a graphical representation (e.g., on paper or a computer screen), a physical representation (e.g., a gel or array) or a digital representation stored in a computer-readable medium. Each map corresponds to a particular status of the disease (e.g., absence of disease, OA, early OA and late OA), and thus provides a template for comparison to a patient sample. In certain preferred embodiments, maps are generated from a plurality of samples obtained from a significant number of normal individuals or individuals with the same stage/status of OA. Maps may be established for individuals with matched age, sex and body mass index.

The term “computer readable medium” refers to any device or system for storing or providing information (e.g., data and instructions) to a computer processor. Examples of computer readable media include, but are not limited to, DVDs, CDs, hard disk drives, magnetic tape and servers for streaming media over networks.

The terms “compound” and “agent” are used herein interchangeably. They refer to any naturally occurring or non-naturally occurring (i.e., synthetic or recombinant) molecule, such as a biological macromolecule (e.g., nucleic acid, polypeptide or protein), organic or inorganic molecule, or an extract made from biological materials such as bacteria, plants, fungi, or animal (particularly mammalian, including human) cells or tissues. The compound may be a single molecule or a mixture or complex of at least two molecules.

The term “candidate compound” refers to a compound or agent (as defined above) that is to be tested for an activity of interest. In the screening methods of the present invention, candidate compounds are evaluated for their ability to modulate (e.g., increase or decrease) the expression level of one or more of the biomarkers provided herein. Particularly interesting are candidate compounds that can restore the expression profile of one or more disease indicative biomarkers of a patient with OA to an expression profile more similar to that of an individual afflicted with an earlier stage of the disease or to that of a normal individual. Such compounds are potential “OA therapeutic agents”.

As used herein, the term “effective amount” refers to an amount of a compound or agent that is sufficient to fulfill its intended purpose(s). In the context of the present invention, the purpose(s) may be, for example: to modulate the expression of at least one inventive biomarker; and/or to delay or prevent the onset of OA; and/or to slow down or stop the progression, aggravation, or deterioration of the symptoms of OA; and/or to bring about amelioration of the symptoms of OA, and/or to cure OA.

The term “system” and “biological system” are used herein interchangeably. A system may be any biological entity that can express or comprise at least one inventive biomarker. In the context of the present invention, in vitro, in vivo, and ex vivo systems are considered; and the system may be a cell, a biological fluid, a biological tissue, or an animal. For example, a system may originate from a living subject (e.g., it may be obtained by drawing blood, or by performing needle biopsy), or from a deceased subject (e.g., it may be obtained at autopsy).

A “pharmaceutical composition” is defined herein as comprising at least one compound of the invention (i.e., a candidate compound identified by an inventive screening method as a modulator of the expression of at least one inventive biomarker), and at least one pharmaceutically acceptable carrier.

As used herein, the term “pharmaceutically acceptable carrier” refers to a carrier medium which does not interfere with the effectiveness of the biological activity of the active ingredients and which is not excessively toxic to the host at the concentrations at which it is administered. The term includes solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, absorption delaying agents, and the like. The use of such media and agents for pharmaceutically active substances is well known in the art (see, for example, Remington's Pharmaceutical Sciences, E. W. Martin, 18th Ed., 1990, Mack Publishing Co., Easton, Pa.).

The term “treatment” is used herein to characterize a method that is aimed at (1) delaying or preventing the onset of OA; or (2) slowing down or stopping the progression, aggravation, or deterioration of the symptoms of the condition; or (3) bringing about ameliorations of the symptoms of the condition; or (4) curing the condition. A treatment may be administered prior to the onset of the disease, for a prophylactic or preventive action. It may also be administered after initiation of the disease, for a therapeutic action.

The present invention relates to improved systems and strategies for the diagnostic, characterization, and staging of OA. In particular, the present invention provides the identity of biomarkers whose expression has been found to correlate with OA and OA progression.

In one aspect, the present invention provides the identity of a set of proteins indicative of OA identified using high-throughput proteomics technology. The protein markers indicative of OA are listed in Tables 1, 2, 3, 4, 5, and 6. More specifically, by analyzing samples of serum protein depleted, age-matched synovial fluid obtained from healthy patients and from patients with early OA or late OA, it was found that the proteins listed in Tables 1, 2, 3, 4, 5 and 6 can be used to discriminate between normal/healthy and early OA and normal/healthy and late OA. It was also found that the proteins listed in Tables 1, 2, 3, 4, 5 and 6 can be used to discriminate between early OA, late OA, and healthy individuals.

The samples of synovial fluid obtained from patients with early and late OA compared to samples of synovial fluid obtained from normal individuals exhibit differing expression levels (i.e., increased expression levels and decreased levels of expression) of the proteins listed of the proteins listed in Tables 1, 2, 3, 4, 5, and 6. Therefore, the expression profiles of the proteins presented in Tables 1, 2, 3, 4, 5, and 6 can be used to diagnose OA as well as to determine the presence and/or degree of advancement of the disease (i.e., to determine the stage of the disease).

Other OA biomarkers provided by the present invention include nucleic acid molecules comprising polynucleotide sequences coding for the inventive protein markers described above (or analogs and fragments thereof) and polynucleotides that hybridize with portions of these nucleic acid molecules.

Information on expression levels of a given set of biomarkers obtained using biological samples from individuals afflicted with a particular stage of the disease (e.g., healthy subjects, patients with OA, with early OA, or with late OA) may be grouped to form an OA expression profile map. Preferably, an OA expression profile map results from the study of a large number of individuals with the same disease stage/status. In certain embodiments, an OA expression profile map is established using samples from individuals with matched age, sex, and body index. Each expression profile map provides a template for comparison to biomarker expression patterns generated from unknown biological samples. OA expression profile maps may be presented as a graphical representation (e.g., on paper or a computer screen), a physical representation (e.g., a gel or array) or a digital representation stored in a computer-readable medium.

As will be appreciated by those of ordinary skill in the art, sets of biomarkers whose expression profiles correlate with OA, can discriminate between different stages of the disease may be used to identify, study or characterize unknown biological samples. Accordingly, the present invention provides methods for characterizing biological samples obtained from a subject suspected of having OA, for diagnosing OA in a subject, and for assessing the advancement of OA in a subject. In such methods, the biomarkers' expression levels determined for a biological sample obtained from the subject are compared to the levels in one or more control samples. The control samples may be obtained from a healthy individual (or a group of healthy individuals), from an individual (or group of individuals) afflicted with OA, and/or from an individual (or group of individuals) afflicted with a specific stage of the disease (e.g., early OA or late OA). As mentioned above, the control expression levels of the biomarkers of interest are preferably determined from a significant number of individuals, and an average or mean is obtained. In certain preferred embodiments, the expression levels determined for the biological sample under investigation are compared to at least one expression profile map for OA, as described above.

In other embodiments, the control protein expression profile is a healthy or normal expression profile, and the difference is indicative of early or late stage osteoarthritis. In such embodiments, the difference may be selected from the group consisting of an increase or decrease in the level of expression of one or more proteins selected from the group consisting of fibronectin precursor, alpha-2-macroglobulin precursor, Chain B Structure of Complement C3b, complement factor H, fibronectin 1 isoform 3 preproprotein, collagen type IV alpha 1, alph 2 type IV collagen preprotein, inter-alpha-trypsin inhibitor, C-terminal inter-alpha trypsin inhibitor, phosphatidylinositol-glycan-specific phospholipase D1, afamin precursor, complement component 6 isoform CRA_b, inter-alpha-trypsin inhibitor heavy chain-related protein, Chain A Crystal Structure of human Galectin-7, COMP, ALB protein, gelsolin isoform a precursor, complement factor B, fibulin-1 isoform D precursor, valosin-containing protein, Vitamin D-binding protein precursor, complement component 2 precursor, annexin A2, Annexin A2 isoform 2, hornerin precursor, complement component 1 s subcomponent, ASPIC, Vitamin K-dependent protein, plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7 (psoriasin), coagulation factor XIII, B Chain Alpha-Ferrous-Carbonmonoxy, coagulation factor II precursor, insulin-like growth factor binding protein acid labile subunit, histidine-rich glycoprotein precursor, phospholipid transfer protein isoform a precursor, antithrombin III, glucosamine(N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain, vitronectin, biotinidase precursor, acid labile subunit, alpha-1-B-glycoprotein, thrombin inhibitor, C9 complement protein, Coagulation factor XIII B chain precursor, hemopexin precursor, vanin 1 precursor, extracellular matrix protein 1 isoform precursor, histidine-rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L precursor, Chain A Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma chain, inter-alpha (globulin) inhibitor H1, alpha-2-antiplasmin precursor, vitronectin precursor, Vitamin K-dependent protein S precursor, complement component 9, GRP78, analogs and fragments thereof; and any combination thereof.

The methods of the invention may be applied to the study of any type of biological samples allowing one or more inventive biomarkers to be assayed. Examples of biological samples include, but are not limited to, urine, blood, blood products, joint fluid, saliva, and synovial fluid. The biological samples used in the practice of the inventive methods of diagnostic may be fresh or frozen samples collected from a subject, or archival samples with known diagnosis, treatment and/or outcome history. Biological samples may be collected by any non-invasive means, such as, for example, by drawing blood from a subject, or using fine needle aspiration or needle biopsy. Alternatively, biological samples may be collected by an invasive method, including, for example, surgical biopsy.

In certain embodiments, the inventive methods are performed on the biological sample itself without or with limited processing of the sample.

In other embodiments, the inventive methods are performed at the single cell level (e.g., isolation of cells from the biological sample). However, in such embodiments, the inventive methods are preferably performed using a sample comprising many cells, where the assay is “averaging” expression over the entire collection of cells present in the sample. Preferably, there is enough of the biological sample to accurately and reliably determine the expression of the set of biomarkers of interest. Multiple biological samples may be taken from the same tissue/body part in order to obtain a representative sampling of the tissue.

In still other embodiments, the inventive methods are performed on a protein extract prepared from the biological sample. Preferably, the protein extract contains the total protein content. However, the methods may also be performed on extracts containing one or more of: membrane proteins, nuclear proteins, and cytosolic proteins. Methods of protein extraction are well known in the art (see, for example “Protein Methods”, D. M. Bollag et al., 2nd Ed., 1996, Wiley-Liss; “Protein Purification Methods: A Practical Approach”, E. L. Harris and S. Angal (Eds.), 1989; “Protein Purification Techniques: A Practical Approach”, S. Roe, 2nd Ed., 2001, Oxford University Press; “Principles and Reactions o/Protein Extraction, Purification, and Characterization”, H. Ahmed, 2005, CRC Press: Boca Raton, Fla.). Numerous different and versatile kits can be used to extract proteins from bodily fluids and tissues, and are commercially available from, for example, BioRad Laboratories (Hercules, Calif.), BD Biosciences Clontech (Mountain View, Calif.), Chemicon International, Inc. (Temecula, Calif.), Calbiochem (San Diego, Calif.), Pierce Biotechnology (Rockford, Ill.), and Invitrogen Corp. (Carlsbad, Calif.). User Guides that describe in great detail the protocol to be followed are usually included in all these kits. Sensitivity, processing time and costs may be different from one kit to another. One of ordinary skill in the art can easily select the kites) most appropriate for a particular situation. After the protein extract has been obtained, the protein concentration of the extract is preferably standardized to a value being the same as that of the control sample in order to allow signals of the protein markers to be quantitated. Such standardization can be made using photometric or spectrometric methods or gel electrophoresis.

In yet other embodiments, the inventive methods are performed on nucleic acid molecules extracted from the biological sample. For example, RNA may be extracted from the sample before analysis. Methods of RNA extraction are well known in the art (see, for example, J. Sambrook et al., “Molecular Cloning: A Laboratory Manual”, 1989, 2nd Ed., Cold Spring Harbor Laboratory Press: Cold Spring Harbor, N.Y.). Most methods of RNA isolation from bodily fluids or tissues are based on the disruption of the tissue in the presence of protein denaturants to quickly and effectively inactivate RNAses. Isolated total RNA may then be further purified from the protein contaminants and concentrated by selective ethanol precipitations, phenol/chloroform extractions followed by isopropanol precipitation or cesium chloride, lithium chloride or cesium trifluoroacetate gradient centrifugations. Kits are also available to extract RNA (i.e., total RNA or mRNA) from bodily fluids or tissues and are commercially available from, for example, Ambion, Inc. (Austin, Tex.), Amersham Biosciences (Piscataway, N.J.), BD Biosciences Clontech (Palo Alto, Calif.), BioRad Laboratories (Hercules, Calif.), GIBCO BRL (Gaithersburg, Md.), and Qiagen, Inc. (Valencia, Calif.).

In certain embodiments, after extraction, mRNA is amplified, and transcribed into cDNA, which can then serve as template for multiple rounds of transcription by the appropriate RNA polymerase. Amplification methods are well known in the art (see, for example, A. R. Kimmel and S. L. Berger, Methods Enzymol. 1987, 152: 307-316; J. Sambrook et al., “Molecular Cloning: A Laboratory Manual”, 1989, 2nd Ed., Cold Spring Harbour Laboratory Press: New York; “Short Protocols in Molecular Biology”, F. M. Ausubel (Ed.), 2002, 5th Ed., John Wiley & Sons; U.S. Pat. Nos. 4,683,195; 4,683,202 and 4,800,159). Reverse transcription reactions may be carried out using non-specific primers, such as an anchored oligo-dT primer, or random sequence primers, or using a target-specific primer complementary to the RNA for each probe being monitored, or using thermostable DNApolymerases (such as avian myeloblastosis virus reverse transcriptase or Moloney murine leukemia virus reverse transcriptase).

The diagnostic methods of the present invention generally involve the determination of expression levels of a plurality (i.e., one or more, e.g., at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more) of polypeptides in a biological sample obtained from a subject. Determination of protein expression levels in the practice of the inventive methods may be performed by any suitable method (see, for example, E. Harlow and A. Lane, “Antibodies: A Laboratories Manual”, 1988, Cold Spring Harbor Laboratory Cold Spring Harbor, N.Y.).

In general, protein expression levels are determined by contacting a biological sample isolated from a subject with binding agents for one or more of the protein markers; detecting, in the sample, the levels of polypeptides that bind to the binding agents; and comparing the levels of polypeptides in the sample with the levels of polypeptides in a control sample. As used herein, the term “binding agent” refers to an entity such as a polypeptide or antibody that specifically binds to an inventive protein marker. An entity “specifically binds” to a polypeptide if it reacts/interacts at a detectable level with the polypeptide but does not react/interact detectably with peptides containing unrelated sequences or sequences of different polypeptides.

In certain embodiments, the binding agent is a ribosome, with or without a peptide component, an RNA molecule, or a polypeptide (e.g., a polypeptide that comprises a polypeptide sequence of a protein marker, a peptide variant thereof, or a non-peptide mimetic of such a sequence).

In other embodiments, the binding agent is an antibody specific for a protein marker of the invention. Suitable antibodies for use in the methods of the present invention include monoclonal and polyclonal antibodies, immunologically active fragments (e.g., Fab or (Fab)₂fragments), antibody heavy chains, humanized antibodies, antibody light chains, and chimeric antibodies. Antibodies, including monoclonal and polyclonal antibodies, fragments and chimeras, may be prepared using methods known in the art (see, for example, R. G. Mage and E. Lamoyi, in “Monoclonal Antibody Production Techniques and Applications”, 1987, Marcel Dekker, Inc.: New York, pp. 79-97; G. Kohler and C. Milstein, Nature, 1975, 256: 495-497; D. Kozbor et al., J. Immunol. Methods, 1985, 81: 31-42; and R. J. Cote et al., Proc. Natl. Acad. Sci. 1983, 80: 2026-203; R. A. Lerner, Nature, 1982, 299: 593-596; A. C. Nairn et al., Nature, 1982, 299: 734-736; A. J. Czernik et al., Methods Enzymol. 1991, 201: 264-283; A. J. Czernik et al., Neuromethods: Regulatory Protein Modification: Techniques & Protocols, 1997, 30: 219-250; A. J. Czemik et al., NeuroNeuroprotocols, 1995, 6: 56-61; H. Zhang et al., J. Biol. Chem. 2002, 277: 39379-39387; S. L. Morrison et al., Proc. Natl. Acad. Sci., 1984, 81: 6851-6855; M. S. Neuberger et al., Nature, 1984, 312: 604-608; S. Takeda et al., Nature, 1985, 314: 452-454). Antibodies to be used in the methods of the invention can be purified by methods well known in the art (see, for example, S. A. Minden, “Monoclonal Antibody Purification”, 1996, IBC Biomedical Library Series: Southbridge, Mass.). For example, antibodies can be affinity purified by passage over a column to which a protein marker or fragment thereof is bound. The bound antibodies can then be eluted from the column using a buffer with a high salt concentration.

Instead of being prepared, antibodies to be used in the methods of the present invention may be obtained from scientific or commercial sources.

In certain embodiments, the binding agent is directly or indirectly labeled with a detectable moiety. The role of a detectable agent is to facilitate the detection step of the diagnostic method by allowing visualization of the complex formed by binding of the binding agent to the protein marker (or analog or fragment thereof). Preferably, the detectable agent is selected such that it generates a signal which can be measured and whose intensity is related (preferably proportional) to the amount of protein marker present in the sample being analyzed. Methods for labeling biological molecules such as polypeptides and antibodies are well-known in the art (see, for example, “Affinity Techniques. Enzyme Purification. Part B”, Methods in Enzymol., 1974, Vol. 34, W. B. Jakoby and M. Wilneck (Eds.), Academic Press: New York, N.Y.; and M. Wilchek and E. A. Bayer, Anal. Biochem., 1988, 171: 1-32).

Any of a wide variety of detectable agents can be used in the practice of the present invention. Suitable detectable agents include, but are not limited to: various ligands, radionuclides, fluorescent dyes, chemiluminescent agents, microparticles (such as, for example, quantum dots, nanocrystals, phosphors and the like), enzymes (such as, for example, those used in an ELISA, i.e., horseradish peroxidase, beta-galactosidase, luciferase, alkaline phosphatase), colorimetric labels, magnetic labels, and biotin, dioxigenin or other haptens and proteins for which antisera or monoclonal antibodies are available.

In certain embodiments, the binding agents (e.g., antibodies) may be immobilized on a carrier or support (e.g., a bead, a magnetic particle, a latex particle, a microtiter plate well, a cuvette, or other reaction vessel). Examples of suitable carrier or support materials include agarose, cellulose, nitrocellulose, dextran, Sephadex, Sepharose, liposomes, carboxymethyl cellulose, polyacrylamides, polystyrene, gabbros, filter paper, magnetite, ion-exchange resin, plastic film, plastic tube, glass, polyamine-methyl vinylether-maleic acid copolymer, amino acid copolymer, ethylene-maleic acid copolymer, nylon, silk, and the like. Binding agents may be indirectly immobilized using second binding agents specific for the first binding agents (e.g., mouse antibodies specific for the protein markers may be immobilized using sheep anti-mouse IgG Fc fragment specific antibody coated on the carrier or support).

Protein expression levels in the diagnostic methods of the present invention may be determined using immunoassays. Examples of such assays are radioimmunoassays, enzyme immunoassays (e.g., ELISA), immunofluorescence immunoprecipitation, latex agglutination, hemagglutination, and histochemical tests, which are conventional methods well-known in the art. As will be appreciated by one skilled in the art, the immunoassay may be competitive or noncompetitive. Methods of detection and quantification of the signal generated by the complex formed by binding of the binding agent with the protein marker will depend on the nature of the assay and of the detectable moiety (e.g., fluorescent moiety).

Alternatively, the protein expression levels may be determined using mass spectrometry based methods or image (including use of labeled ligand) based methods known in the art for the detection of proteins. Other suitable methods include proteomics-based methods. Proteomics, which studies the global changes of protein expression in a sample, typically includes the following steps: (I) separation of individual proteins in a sample by electrophoresis (2-D PAGE), (2) identification of individual proteins recovered from the gel (e.g., by mass spectrometry or N-terminal sequencing), and (3) analysis of the data using bioinformatics.

As already mentioned above, the diagnostic methods of the present invention may involve determination of the expression levels of a set of nucleic acid molecules comprising polynucleotide sequences coding for an inventive protein marker. Determination of expression levels of nucleic acid molecules in the practice of the inventive methods may be performed by any suitable method, including, but not limited to, Southern analysis, Northern analysis, polymerase chain reaction (PCR) (see, for example, U.S. Pat. Nos. 4,683,195; 4,683,202, and 6,040,166; “PCR Protocols: A Guide to Methods and Applications”, Innis et al. (Eds.), 1990, Academic Press: New York), reverse transcriptase PCR (RT-PCT), anchored PCR, competitive PCR (see, for example, U.S. Pat. No. 5,747,251), rapid amplification of cDNA ends (RACE) (see, for example, “Gene Cloning and Analysis: Current Innovations, 1997, pp. 99-115); ligase chain reaction (LCR) (see, for example, EP 01 320308), one-sided PCR (Ohara et al., Proc. Natl. Acad. Sci., 1989, 86: 5673-5677), in situ hybridization, Taqman based assays (Holland et al., Proc. Natl. Acad. Sci., 1991, 88:7276-7280), differential display (see, for example, Liang et al., Nucl. Acid. Res., 1993, 21: 3269-3275) and other RNA fingerprinting techniques, nucleic acid sequence based amplification (NASBA) and other transcription based amplification systems (see, for example, U.S. Pat. Nos. 5,409,818 and 5,554,527), Qbeta Replicase, Strand Displacement Amplification (SDA), Repair Chain Reaction (RCR), nuclease protection assays, subtraction-based methods, Rapid-Scan™, and the like.

Nucleic acid probes for use in the detection of polynucleotide sequences in biological samples may be constructed using conventional methods known in the art. Suitable probes may be based on nucleic acid sequences encoding at least 5 sequential amino acids from regions of nucleic acids encoding a protein marker, and preferably comprise about 15 to about 50 nucleotides. A nucleic acid probe may be labeled with a detectable moiety, as mentioned above in the case of binding agents. The association between the nucleic acid probe and detectable moiety can be covalent or non-covalent. Detectable moieties can be attached directly to nucleic acid probes or indirectly through a linker (E. S. Mansfield et al., Mol. Cell. Probes, 1995, 9: 145-156). Methods for labeling nucleic acid molecules are well-known in the art (for a review of labeling protocols, label detection techniques and recent developments in the field, see, for example, L. J. Kricka, Ann. Clin. Biochem. 2002, 39: 114-129; R. P. van Gijlswijk et al., Expert Rev. Mol. Diagn. 2001, 1: 81-91; and S. Joos et al., J. Biotechnol. 1994, 35:135-153).

Nucleic acid probes may be used in hybridization techniques to detect polynucleotides encoding the protein markers. The technique generally involves contacting an incubating nucleic acid molecules in a biological sample obtained from a subject with the nucleic acid probes under conditions such that specific hybridization takes place between the nucleic acid probes and the complementary sequences in the nucleic acid molecules. After incubation, the non-hybridized nucleic acids are removed, and the presence and amount of nucleic acids that have hybridized to the probes are detected and quantified.

Detection of nucleic acid molecules comprising polynucleotide sequences coding for a protein marker may involve amplification of specific polynucleotide sequences using an amplification method such as PCR, followed by analysis of the amplified molecules using techniques known in the art. Suitable primers can be routinely designed by one skilled in the art. In order to maximize hybridization under assay conditions, primers and probes employed in the methods of the invention generally have at least 60%, preferably at least 75% and more preferably at least 90% identity to a portion of nucleic acids encoding a protein marker.

Hybridization and amplification techniques described herein may be used to assay qualitative and quantitative aspects of expression of nucleic acid molecules comprising polynucleotide sequences coding for the inventive protein markers.

Alternatively, oligonucleotides or longer fragments derived from nucleic acids encoding each protein marker may be used as targets in a microarray. A number of different array configurations and methods of their production are known to those skilled in the art (see, for example, U.S. Pat. Nos. 5,445,934; 5,532,128; 5,556,752; 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,472,672; 5,527,681; 5,529,756; 5,545,531; 5,554,501; 5,561,071; 5,571,639; 5,593,839; 5,599,695; 5,624,711; 5,658,734; and 5,700,637). Microarray technology allows for the measurement of the steady-state level of large numbers of polynucleotide sequences simultaneously. Microarrays currently in wide use include cDNA arrays and oligonucleotide arrays. Analyses using microarrays are generally based on measurements of the intensity of the signal received from a labeled probe used to detect a cDNA sequence from the sample that hybridizes to a nucleic acid probe immobilized at a known location on the microarray (see, for example, U.S. Pat. Nos. 6,004,755; 6,218,114; 6,218,122; and 6,271,002). Array-based gene expression methods are known in the art and have been described in numerous scientific publications as well as in patents (see, for example, M. Schena et al., Science, 1995, 270: 467-470; M. Schena et al., Proc. Natl. Acad. Sci. USA 1996, 93: 10614-10619; 1. 1. Chen et al., Genomics, 1998, 51: 313324; U.S. Pat. Nos. 5,143,854; 5,445,934; 5,807,522; 5,837,832; 6,040,138; 6,045,996; 6,284,460; and 6,607,885).

Once the expression levels of the biomarkers of interest have been determined (as described above) for the biological sample being analyzed, they are compared to the expression levels in one or more control samples or to at least one expression profile map for OA. Comparison of expression levels according to methods of the present invention is preferably performed after the expression levels obtained have been corrected for both differences in the amount of sample assayed and variability in the quality of the sample used (e.g., amount of protein extracted, or amount and quality of mRNA tested). Correction may be carried out using different methods well-known in the art. For example, the protein concentration of a sample may be standardized using photometric or spectrometric methods or gel electrophoresis (as already mentioned above) before the sample is analyzed. In case of samples containing nucleic acid molecules, correction may be carried out by normalizing the levels against reference genes (e.g., housekeeping genes) in the same sample. Alternatively or additionally, normalization can be based on the mean or median signal (e.g., Ct in the case of RT-PCR) of all assayed genes or a large subset thereof (global normalization approach).

For a given set of biomarkers, comparison of an expression pattern obtained for a biological sample against an expression profile map established for a particular stage of OA may comprise comparison of the normalized expression levels on a biomarker-by-biomarker basis and/or comparison of ratios of expression levels within the set of biomarkers. In addition, the expression pattern obtained for the biological sample being analyzed, may be compared against each of the expression profile maps (e.g., expression profile map for non-OA, expression profile map for OA, expression profile map for early OA, and expression profile map for late OA) or against an expression profile that defines delineations made based upon all the OA expression profile maps.

Using methods described herein, skilled physicians may select and prescribe treatments adapted to each individual patient based on the diagnosis and disease staging provided to the patient through determination of the expression levels of the inventive biomarkers. In particular, the present invention provides physicians with a non-subjective means to diagnose early OA, which will allow for early treatment, when intervention is likely to have its greatest effect, potentially preventing pain and long-term disability and improving patient's quality of life. Selection of an appropriate therapeutic regimen for a given patient may be made based solely on the diagnosis/staging provided by the inventive methods. Alternatively, the physician may also consider other clinical or pathological parameters used in existing methods to diagnose OA and assess its advancement.

Furthermore, the methods of OA diagnosis and OA staging provided by the present invention allow the disease to be monitored even when signs of cartilage destruction would not be visible or when changes in joint spaces would not be detectable on X-ray images.

In another aspect, the present invention provides kits comprising materials useful for carrying out diagnostic methods according to the present invention. The diagnosis and staging procedures described herein may be performed by diagnostic laboratories, experimental laboratories, or practitioners. The invention provides kits, which can be used in these different settings.

Materials and reagents for characterizing biological samples, diagnosing OA in a subject, and/or staging OA in a subject according to the inventive methods may be assembled together in a kit. In certain embodiments, an inventive kit comprises at least one reagent that specifically detects expression levels of one or more inventive biomarkers, and instructions for using the kit according to a method of the invention. Each kit may preferably include the reagent, which renders the procedure specific. Thus, for detecting/quantifying a protein marker (or an analog or fragment thereof), the reagent that specifically detects expression levels of the protein may be an antibody that specifically binds to the protein marker (or analog or fragment thereof). For detecting/quantifying a nucleic acid molecule comprising a polynucleotide sequence coding a protein marker, the reagent that specifically detects expression levels may be a nucleic acid probe complementary to the polynucleotide sequence (e.g., cDNA or an oligonucleotide). The nucleic acid probe may or may not be immobilized on a substrate surface (e.g., beads, a microarray, and the like).

Depending on the procedure, the kit may further comprise one or more of, extraction buffer and/or reagents, amplification buffer and/or reagents, hybridization buffer and/or reagents, immunodetection buffer and/or reagents, labeling buffer and/or reagents, and detection means. Protocols for using these buffers and reagents for performing different steps of the procedure may be included in the kit.

The reagents may be supplied in a solid (e.g., lyophilized) or liquid form. The kits of the present invention may optionally comprise different containers (e.g., vial, ampoule, test tube, flask or bottle) for each individual buffer and/or reagent. Each component will generally be suitable as aliquoted in its respective container or provided in a concentrated form. Other containers suitable for conducting certain steps of the disclosed methods may also be provided. The individual containers of the kit are preferably maintained in close confinement for commercial sale.

In certain embodiments, the kits of the present invention further comprise control samples. In other embodiments, the inventive kits comprise at least one expression profile map for OA and/or OA progression as described herein for use as comparison template. Preferably, the expression profile map is digital information stored in a computer-readable medium.

Instructions for using the kit, according to one or more methods of the invention, may comprise instructions for processing the biological sample obtained from the subject, and/or for performing the test, instructions for interpreting the results. As well as a notice in the form prescribed by a governmental agency (e.g., FDA) regulating the manufacture, use or sale of pharmaceuticals or biological products.

As noted above, the inventive biomarkers whose expression profiles correlate with osteoarthritis and/or osteoarthritis progression are attractive targets for the identification of new therapeutic agents (e.g., using screens to detect compounds or substances that inhibit or enhance the expression of these biomarkers). Accordingly, the present invention provides methods for the identification of compounds potentially useful for treating osteoarthritis or modulating osteoarthritis progression.

The inventive methods comprise incubating a biological system, which expresses at least one inventive biomarker, with a candidate compound under conditions and for a time sufficient for the candidate compound to modulate the expression of the biomarker, thereby obtaining a test system; incubating the biological system under the same conditions and for the same time absent the candidate compound, thereby obtaining a control system; measuring the expression level of the biomarker in the test system; measuring the expression level of the biomarker in the control system; and determining that the candidate compound modulates the expression of the biomarker if the expression level measured in the test system is less than or greater than the expression level measured in the control system.

The assay and screening methods of the present invention may be carried out using any type of biological systems, e.g., a cell or cells, a biological fluid, a biological tissue, or an animal. In certain embodiments, the methods are carried out using a system that can exhibit cartilage degeneration due to OA (e.g., an animal model, or whole or portion of a body part, e.g., the knee). In other embodiments, the methods are carried out using a biological entity that expresses or comprises at least one inventive biomarker (e.g., a cell or a sample of blood, urine, saliva, or synovial fluid).

In certain preferred embodiments, the assay and screening methods of the present invention are carried out using cells that can be grown in standard tissue culture plastic ware. Such cells include all appropriate normal and transformed cells derived from any recognized sources. Preferably, cells are of mammalian (human or animal, such as rodent or simian) origin. More preferably, cells are of human origin. Mammalian cells may be of any organ or tissue origin (e.g., bone, cartilage, or synovial fluid) and of any cell types as long as the cells express at least one inventive biomarker.

Cells to be used in the practice of the methods of the present invention may be primary cells, secondary cells, or immortalized cells (e.g., established cell lines). They may be prepared by techniques well known in the art (for example, cells may be isolated from bone, cartilage or synovial fluid) or purchased from immunological and microbiological commercial resources (for example, from the American Type Culture Collection, Manassas, Va.). Alternatively or additionally, cells may be genetically engineered to contain, for example, a gene of interest.

Selection of a particular cell type and/or cell line to perform an assay according to the present invention will be governed by several factors such as the nature of the biomarker whose expression is to be modulated and the intended purpose of the assay. For example, an assay developed for primary drug screening (i.e., first round(s) of screening) is preferably performed using established cell lines, which are commercially available and usually relatively easy to grow, while an assay to be used later in the drug development process is preferably performed using primary and secondary cells, which are generally more difficult to obtain, maintain and/or grow than immortalized cells but which represent better experimental models for in vivo situation. Examples of established cell lines that can be used in the practice of the assay and screening methods of the present invention include fibroblastic and/or osseously derived cell lines. Primary and secondary cells that can be used in the inventive screening methods include, but are not limited to, chondrocytes and osteocytes.

Cells to be used in the inventive assays may be cultured according to standard cell culture techniques. For example, cells are often grown in a suitable vessel in a sterile environment at 37° C. in an incubator containing a humidified 95% air-5% CO₂atmosphere. Vessels may contain stirred or stationary cultures. Various cell culture media may be used including media containing undefined biological fluids such as fetal calf serum. Cell culture techniques are well known in the art and established protocols are available for the culture of diverse cell types (see, for example, R. I. Freshney, “Culture of Animal Cells: A Manual of Basic Technique”, 2nd Edition, 1987, Alan R. Liss, Inc.).

In certain embodiments, the screening methods are performed using cells contained in a plurality of wells of a multi-well assay plate. Such assay plates are commercially available, for example, from Stratagene Corp. (La Jolla, Calif.) and Coming Inc. (Acton, Mass.) and include, for example, 48-well, 96-well, 384-well and 1536-well plates.

As will be appreciated by those of ordinary skill in the art, any kind of compounds or agents can be tested using the inventive methods. A candidate compound may be a synthetic or natural compound; it may be a single molecule or a mixture or complex of different molecules. In certain embodiments, the inventive methods are used for testing one or more compounds. In other embodiments, the inventive methods are used for screening collections or libraries of compounds. As used herein, the term “collection” refers to any set of compounds, molecules or agents, while the term “library” refers to any set of compounds, molecules or agents that are structural analogs.

Collections of natural compounds in the form of bacterial, fungal, plant and animal extracts are available from, for example, Pan Laboratories (Bothell, Wash.) or MycoSearch (Durham, N.C.). Libraries of candidate compounds that can be screened using the methods of the present invention may be either prepared or purchased from a number of companies. Synthetic compound libraries are commercially available from, for example, Comgenex (Princeton, N.J.), Brandon Associates (Merrimack, N.H.), Microsource (New Milford, Conn.), and Aldrich (Milwaukee, Wis.). Libraries of candidate compounds have also been developed by and are commercially available from large chemical companies, including, for example, Merck, Glaxo Welcome, Bristol-Meyers-Squibb, Novartis, Monsanto/Searle, and Pharmacia UpJohn. Additionally, natural collections, synthetically produced libraries and compounds are readily modified through conventional chemical, physical, and biochemical means. Chemical libraries are relatively easy to prepare by traditional automated synthesis, PCR, cloning or proprietary synthetic methods (see, for example, S. H. DeWitt et al., Proc. Natl. Acad. Sci. U.S.A. 1993, 90:6909-6913; R. N. Zuckermann et al., J. Med. Chem. 1994, 37: 2678-2685; Carell et al., Angew. Chem. Int. Ed. Engl. 1994, 33: 2059-2060; P. L. Myers, Curro Opin. Biotechnol. 1997, 8: 701-707).

Useful agents for the treatment of osteoarthritis may be found within a large variety of classes of chemicals, including heterocycles, peptides, saccharides, steroids, and the like. In certain embodiments, the screening methods of the invention are used for identifying compounds or agents that are small molecules (i.e., compounds or agents with a molecular weight <600-700 Da).

The screening of libraries according to the inventive methods will provide “hits” or “leads”, i.e., compounds that possess a desired but not-optimized biological activity. The next step in the development of useful drug candidates is usually the analysis of the relationship between the chemical structure of a hit compound and its biological or pharmacological activity. Molecular structure and biological activity are correlated by observing the results of systemic structural modification on defined biological end-points. Structure-activity relationship information available from the first round of screening can then be used to generate small secondary libraries, which are subsequently screened for compounds with higher affinity. The process of performing synthetic modifications of a biologically active compound to fulfill all stereoelectronic, physicochemical, pharmacokinetic, and toxicologic factors required for clinical usefulness is called lead optimization. Candidate compounds identified as potential OA therapeutic agents by screening methods of the present invention can similarly be subjected to a structure-activity relationship analysis, and chemically modified to provide improved drug candidates. The present invention also encompasses these improved drug candidates.

In the screening methods of the present invention, a candidate compound is identified as a modulator of the expression of at least one inventive biomarker if the expression level of the biomarker in the test sample is lower or greater than the expression level of the same biomarker in the control sample. Reproducibility of the results obtained using methods of the present invention may be tested by performing the analysis more than once with the same concentration of the same candidate compound (for example, by incubating cells in more than one well of an assay plate). Additionally, since candidate compounds may be effective at varying concentrations depending on the nature of the compound and the nature of its mechanism(s) of action, varying concentrations of the candidate compound may be tested (for example, by addition of different concentrations of the candidate compound in different wells containing cells in an assay plate). Generally, candidate compound concentrations from about 1 μM to about 10 mM are used for screening. Preferred screening concentrations are between about 10 μM and about 100 μM.

In certain embodiments, the methods of the invention further involve the use of one or more negative or positive control compounds. A positive control compound may be any molecule or agent that is known to modulate the expression of at least one biomarker studied in the screening assay. A negative control compound may be any molecule or agent that is known to have no detectable effects on the expression of at least one biomarker studied in the screening assay. In these embodiments, the inventive methods further comprise comparing the modulating effects of the candidate compound to the modulating effects (or absence thereof) of the positive (or negative) control compound.

As will be appreciated by those skilled in the art, it is generally desirable to further characterize the compounds identified by the inventive screening methods. For example, if a candidate compound has been identified as a modulator of the expression of a specific biomarker in a given cell culture system (e.g., an established cell line), it may be desirable to test this ability in a different cell culture system (e.g., primary or secondary cells). Alternatively or additionally, it may be desirable to evaluate the effects of the candidate compound on the expression of one or more other inventive biomarkers. It may also be desirable to perform pharmacokinetics and toxicology studies.

A candidate compound identified by the screening methods of the invention may also be further tested in assays that allow for the determination of the compound's properties in vivo. Suitable animal models of osteoarthritis are known in the art. In general, these models fall into two categories, spontaneous and induced (surgical instability or genetic manipulation). Animal models of naturally occurring OA occur in knee joints of guinea pigs, mice, and Syrian hamsters. Commonly used surgical instability models include medial meniscal tear in guinea pigs and rats, medial or lateral partial meniscectomy in rabbits, medial partial or total meniscectomy or anterior cruciate transection in dogs. Transgenic models have been developed in mice. Examples of animal models of osteoarthritis suitable for testing the candidate compounds identified as potential OA therapeutic agents include, but are not limited to, those described in M. J. Pond and G. Nuki, Ann. Rheum. Dis., 1973, 32: 387-388; T. Videman, Acta Orthop. Scand., 1982, 53: 339-347; S. B. Christensen, Scand. J. Rheumatol., 1983, 12: 343-349; A. M. Bendele et al., Vet. Pathol., 1987, 24: 436-443; K. D. Brandt et al., J. Rheumatol., 1991, 18: 436-446; K. D. Brandt, Ann. NY Acad. Sci., 1994, 732: 199-205; C. S. Carlson et al., J. Orthop. Res., 1994, 12: 331-339; A. G. Fam et al., Arthritis Rheum., 1995, 38: 201-210; K. W. Marshall and A. D. Chan, J. Rheumatol., 1996, 23: 344-350; H. J. Helminen et al., Rheumatol., 2002, 41: 848-856 and references cited therein; and J. L. Henry, Novartis Found Symp., 2004, 260: 139-145.

The present invention also provides pharmaceutical compositions, which comprise, as active ingredient, an effective amount of at least one compound identified by an inventive screening assay as a modulator of the expression of at least one biomarker or one set of biomarkers disclosed herein. The pharmaceutical composition may be formulated using conventional methods well known in the art. Such compositions include, in addition to the active ingredient(s), at least one pharmaceutically acceptable liquid, semi-liquid, or solid diluent acting as pharmaceutical vehicle, excipient or medium, and termed here “pharmaceutically acceptable carrier”.

According to the present invention, an inventive pharmaceutical composition may include one or more OA therapeutic agents of the invention as active ingredients. Alternatively, a pharmaceutical composition containing an effective amount of one OA therapeutic agent may be administered to a patient simultaneously with or sequentially with a pharmaceutical composition containing a different inventive OA therapeutic agent.

In another embodiment of this invention, an inventive OA therapeutic agent, or a pharmaceutical composition thereof, may be administered serially or in combination with conventional therapeutics used in the treatment of OA. Such therapeutics include pain relievers such as acetaminophen; Non-steroidal Anti-inflammatory Drugs (NSAIDs), such as aspirin, ibuprofen, naproxen, and ketoprofen; COX-2 inhibitors; corticosteroids; combination of supplement glucosamine and chondroitin sulfates; and over the counter topical formulations containing capsaicin.

Alternatively or additionally, an inventive OA therapeutic agent, or a pharmaceutical composition thereof, may be administered serially or in combination with conventional therapeutic regimens for the treatment of osteoarthritis including viscosupplementation, surgery, arthroplasty (or joint replacement surgery), arthrodesis (or joint fusion), osteotomy, arthroscopy and cartilage transplantation.

In another aspect, the present invention provides methods for the treatment and/or prevention of osteoarthritis. These methods comprise administering to a subject afflicted with OA, an effective amount of a compound that modulates the expression of at least one inventive biomarker. The compound may be known in the art to act as a modulator of the expression of the at least one biomarker. Alternatively, the compound may have been identified as an OA therapeutic agent by a screening method provided by the present invention.

Subjects suitable to receive a treatment according to the present invention include individuals that have been diagnosed with OA using conventional methods (e.g., radiological examination, clinical observations) as well as individuals that have been diagnosed with OA using diagnostic methods provided herein. Suitable subjects may or may not have previously received traditional treatment for the condition.

A treatment according to the methods of the present invention may consist of a single dose or a plurality of doses over a period of time. An inventive OA therapeutic agent, or pharmaceutical composition thereof, may also be released from a depot form per treatment. The administration may be carried out in any convenient manner such as by injection (subcutaneous, intravenous, intramuscular, intraperitoneal, or the like), oral administration, topical administration, rectal administration, or sublingual administration.

Effective dosages and administration regimens can be readily determined by good medical practice and the clinical condition of the individual patient. The frequency of administration will depend on the pharmacokinetic parameters of the active ingredient(s) and the route of administration. The optimal pharmaceutical formulation can be determined depending upon the route of administration and desired dosage. Such formulations may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the administered compounds.

Depending on the route of administration, a suitable dose may be calculated according to body weight, body surface area, or organ size. Optimization of the appropriate dosage can readily be made by those skilled in the art in light of pharmacokinetic data observed in human clinical trials. The final dosage regimen will be determined by the attending physician, considering various factors which modify the action of drugs, e.g., the drug's specific activity, the severity of the damage and the responsiveness of the patient, the age, condition, body weight, sex and diet of the patient, the severity of any present infection, time of administration and other clinical factors. As studies are conducted, further information will emerge regarding the appropriate dosage levels and duration of treatment for various stages of advancement of OA.

Example

A previous study, using mass spectroscopy-based proteomic techniques in synovial fluid (SF), had identified candidate biomarkers for OA with potential to be developed as highly sensitive and specific tests for disease diagnosis. In this study, patients with OA or healthy controls had their SF fractionated using 1 dimensional SDS gels, gel bands were excised and proteins identified and quantified using mass spectrometry for OA versus control. Due to the complex nature of the SF, this technology has limited ability to identify a larger number of potential biomarkers, and in fact can be expected to be able to sift through only the top 100-200 proteins in the sample. In particular, SF contains many serum proteins that mask information relevant to the disease that could be derived from the diseased synovial tissue. Also, the analytical methods used that compared LC-MS intensities of peptides derived from gel bands in the 1-D gel analysis were not optimal for discerning significant differences, specifically they lacked accurate mass tag information.

In this study, we added a number of novel features to provide more accurate quantification and advanced statistical techniques for determining significance. We increased separation of the protein components in the sample, included a third patient group, that of early OA, and age-matched the samples. We first subjected the SF to immuno-affinity depletion to remove abundant components that are derived from admixture of synovial fluid with serum. This was intended to emphasize the contribution of proteins in the SF preparation that are differentially regulated in diseased versus normal synovial tissue. Second, instead of fractionating the proteins by a 1-D gel method, we used a 2-dimensional method that fractionates the protein by both size and charge. Coupled to the large format gels available, typically 2000-3000 protein forms can be examined for abundance variation. Third, the SF proteins were labeled with fluorescent dyes and samples from multiple groups were run on the same gel to enhance the use of modem statistical methods to examine group based differences with high confidence.

In short, we identified biomarkers in the SF of early OA and late OA patients (versus healthy controls) using Two Dimensional Fluorescence Difference Gel Electrophoresis (2D-DIGE) coupled with mass spectroscopy. Using this method, a variety of alterations that describe the progressive nature of the disease were discovered and potential candidate biomarkers for OA had been found suitable for diagnostic purposes or for evaluating therapeutic response.

Patients with Early Osteoarthritis, Late Osteoarthritis and Controls

Two separate 2D DIGE experiments with different numbers of subjects were performed in this study. In the first experiment, 4 healthy control individuals with same number of patients diagnosed with early and late OA were identified and provided SF samples (12 patients). As stated in a previous study, all samples were collected within our tertiary care referral center and approved by our hospital's institutional review board. All SF samples were snap-frozen in liquid nitrogen immediately after acquisition from the knee joint. In the second experiment, we increased the sample size to 6 controls and same number of patients diagnosed with early and late OA (18 total).

Depletion of SF Samples and 2D DIGE Method
Sample Preparation and Fluorescence Dye Labeling

Immuno-affinity depletion was performed for all human synovial fluid samples to remove high. abundant proteins using a commercial column from Agilent. The proteins samples were then further cleaned (GE Healthcare Clean-Up kit), and protein concentration was determined using the 2D-Quant kit as described by the manufacturer (GE Healthcare). Twelve aliquots from each sample with 25 micrograms of proteins were pooled together to prepare an internal standard.

Gel Electrophoresis and Image Acquisition

Precast immobilized pH gradient strips (pH 3-10 NL, 24 cm) were used for isoelectric focusing and IEF was carried out on an IPGphor2 system (GE Healthcare). The proteins were separated by their pI and the strips were transferred for 2nd dimension SDS-PAGE, which separated the proteins by their molecular weight. After electrophoresis the spots labeled by Cydye in the gel were visualized using the Typhoon 9400 imager (GE Healthcare).

Image Analysis for Differential Protein Expression
Image Analysis by DeCyder Software

To compare protein spots across all gels, image analyses were conducted using DeCyder v6.5 2D Differential Analysis Software (GE Healthcare). Protein spot detection and quantification on a set of images was performed using Differential In•gel Analysis (DIA) module in DeCyder software. Because the internal standard was the same pooled sample within each gel, this effectively normalized all the data. Then images were loaded into the biological variation analysis (BVA) module, which matched multiple images from different gels to perform statistical analysis on differential protein expression levels between multiple groups.

Statistical Analysis of Protein Expression

Differences in protein abundance among the three groups (Healthy, EOA and LOA) were evaluated by a one-way analysis of variance (ANOVA) considered significant at p value <0.05. Gel spots were digested by an automatic in-gel digestion system in 96-well plate and mass spectrometry analysis of the peptide for protein identification was performed on a Finnigan LTQ FT hybrid mass spectrometer (Thermo Electron Corp.).

Database Searching and Criteria for Protein Identification

All MSIMS data derived from the IT instrument above were analyzed using Mascot Daemon (Matrix Science; version 2.2.1) using an indexed Homo sapiens (human) subset database (191437 sequences) created from the National Center for Biotechnology Information (NCBInr) non-redundant databases containing 4626804 sequences assuming the digestion enzyme as trypsin. Search parameters used in this study were: 1) fragment ion mass tolerance of 0.80 Da and peptide mass tolerance limits of 15 ppm, 2) Iodoacetamide derivative of cysteine was specified as a fixed modification (57 Da) and oxidation of methionine was specified as a variable modification (16 Da), 3) One missed cleavage site was allowed, 4) Peptide identifications were accepted at a cut off of p value as 0.05. A positive identification was accepted when a minimum of two peptide monoisotopic masses matched a particular protein with low expectation value (p<0.001).

Results

Decyder software identified the following protein spot numbers (in bold type) as differentially expressed between Early Osteoarthritic (EOA) and Late Osteoarthritic (LOA). Listed below each protein spot number are the potential proteins that each protein spot number represents identified by Mascot search software. The criteria used to determine the results listed below include, Mr, PI, and sequence coverage. These criteria were compared between Mascot search results and Decyder image analysis. These results are listed in Appendix A which includes Tables 1-6.

Other embodiments of the invention will be apparent to those skilled in the art from a consideration of the specification or practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true scope of the invention being indicated by the following claims. All patents, publication, and referenced cited are incorporated by reference in their entirety.

TABLE 1

27
alpha-2-macroglobulin precursor

76
fibronectin precursor, Chain B, Structure of complement C3b, C9 complement

protein

93
no proteins meet the criteria

124
unnamed protein (coagulation factor II precursor)

206
alpha-1-antichymotrypsin

210
alpha-2-macroglobulin precursor, complement component C3, complement

factor H

246
alpha-2-macroglobulin precursor, complement factor H

255
macroglobulin alpha2, complement factor H

265
No proteins meet criteria

292
alpha-2-macroglobulin precursor, complement factor H, trypsin inhibitor, inter-

alpha-trypsin heavy chain H1 precursor

372
alpha-2-macroglobulin precursor, complement factor H isoforma precursor,

gelsolin isoform a precursor

384
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

385
phosphatidylinositol-glycan-specific phospholipase D1 precursor,

ceruloplasmin, inter-alpha-trypsin inhibitor family heavy chain-related protein

393
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

394
inter-alpha-trypsin inhibitor heavy chain H4 precursor, ceruloplasmin

408
glycosylphosphatidylinositol specific phosphatase D1, ceruloplasmin

477
alpha-2-macroglobulin precursor, complement component C6 precursor peptide,

complement factor B

481
pre-pro-alpha(I) collagen

495
Ceruloplasmin, complement component C3, factor H, SERPIN2 protein, gp-

180-carboxypeptidase D-like enzyme

496
inter-alpha-trypsin inhibitor family heavy chain-related protein, Chain B,

Human Complement Component C3, alpha-2-macroglobulin precursor,

ceruloplasmin

644
Fibulin-1 isoform D precursor, inter-alpha-trypsin inhibitor family heavy chain-

related protein, plasminogen, complement factor B, HGF activator,

preproprotein

746
unnamed protein (coagulation factor II precursor), afamin precursor, Vitamin K-

dependent protein, complement component 1, s subcomponent, iinter-alpha-

trypsin inhibitor, ASPIC

805
complement component 3 precursor, plasma kallikrein precursor, annexin A2

isoform 2

840
glucosamine (N-acetyl)-6-sulfatase precursor, unnamed protein (cystic fibrosis

antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding protein A9

849
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII A chain

precursor, peptidoglycan recognition protein L precursor, complement

component 4 binding protein

856
inter-alpha-trypsin inhibitor heavy chain H1 precursor, glucosamine (N-acetyl)-

6-sulfatase precursor, fibrinogen gamma chain, coagulation factor XIII A chain

precursor

864
glucosamine (N-acetyl)-6-sulfatase precursor, Ig mu chain precursor,

phospholipase D3 isoform, moesin

962
complement 9, Chain B, Structure of Complement C3b, alpha-2-antiplasmin

precursor, kininogen, thrombin inhibitor

973
complement 9, Chain A, antithrombin Iii, alpha-2-antiplasmin precursor,

kinninogen, thrombin inhibitor, L-plastin, complement component 1, alpha-1-B-

glycoprotein, hemopexin precursor

1472
complement component C4A, complement component C3, apolipoprotein A-IV

precursor, serum paraoxonase/arylesterase, preprohaptoglobulin, COMP, serpin

peptidase inhibitor, clade I, follistatin-like 1 precursor

1498
complement factor H-related protein 1 precursor, Chain A, Crystal Structure of

Lipid-Free human Apolipoprotein A-1, annexin A2 isoform 2, phospholipase

D3 isoform 2, Chain E, Structure of human transferring receptor-transferrin

complex

TABLE 2

Proteins Differentially Expressed Between EOA vs LOA (12 sample + 18 sample)

2D

Master#
Protein
Mass
pI
Coverage

44
complement component C3
187046
6.02
3%

44
megakaryocyte stimulating factor
150998
9.53
3%

44
PREDICTED: similar to Apolipoprotein(a)
14584
5.79
11%

precursor (Apo(a)) (Lp(a))

44
PREDICTED: similar to Hornerin
187937
9.82
2%

78
fibronectin precursor
260064
5.45
17%

78
ceruloplasmin
98321
5.29
15%

78
putative
2269
9.97
38%

78
hemopexin
13452
6.70
9%

78
PREDICTED: similar to Apolipoprotein(a)
14926
5.79
7%

precursor

78
development and differentiation enhancing factor-
100177
5.98
0%

like 1

78
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

94
fibronectin 1 isoform 3 preproprotein
262656
5.49
18%

94
PREDICTED: similar to Apolipoprotein(a)
14926
5.79
17%

precursor (Apo(a)) (Lp(a))

94
putative
2269
9.79
38%

94
complement component C3
188585
6.02
1%

94
dermcidin preproprotein
11391
6.08
10%

94
megakaryocyte stimulating factor; MSF
152195
9.53
1%

94
Synaptonemal complex protein 1 (SCP-1)
114626
5.85
3%

94
creatine kinase M
43247
6.63
1%

94
predicted: similar to ribosomal protein L36
5528
10.50
21%

94
predicted: similar to cyclin G-associated kinase
148776
9.19
4%

94
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

96
hypothetical protein
272166
5.30
11%

96
alpha-2-macroglobulin precursor
163175
6.00
8%

96
complement component C3
187046
6.02
2%

96
dermcidin preproprotein
11277
6.08
16%

96
hornerin precursor
282199
10.04
2%

123
hypothetical protein
248918
5.92
11%

123
lipoprotein
226369
5.71
5%

123
Chain B, Human Complement Component C3
112869
5.55
2%

123
plasma protease (C1) inhibitor precursor
55147
6.09
3%

123
megakaryocyte stimulating factor
150998
9.53
1%

123
Chain A, Antithrombin Iii
49008
5.95
3%

130
annexin A2 isoform 2
38808
7.57
17%

130
putative
2269
9.79
38%

130
complement component 3 precursor
188569
6.02
7%

130
plasminogen
93233
7.04
5%

130
fibronectin precursor
260064
5.45
0%

130
dermcidin preproprotein
11391
6.08
10%

130
unnamed protein product
112600
8.27
0%

130
hCG2044987
11472
9.73
14%

162
alpha-2-macroglobulin
164600
6.00
27%

162
putative
2269
9.79
38%

162
dermcidin preproprotein
11391
6.08
10%

162
annexin A2 isoform 2
38808
7.57
12%

162
plasminogen
93263
6.89
1%

162
gelsolin isoform a precursor
86043
5.90
2%

162
annexin I
38918
6.57
10%

162
supported by mouse EST AA538043
37423
9.28
2%

(NID: g2284036)

167
alpha-2-macroglobulin precursor
164600
6.00
24%

167
Putative
2269
9.79
38%

167
filaggrin 2
249296
8.45
1%

167
dermcidin preproprotein
11391
6.08
10%

167
complement component C3
188585
6.02
0%

167
Rb1-inducible coiled coil protein
185051
5.31
1%

167
PREDICTED: similar to ribosomal protein L36
5528
10.50
21%

[Pan troglodytes]

167
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
3%

167
chromosome 14 open reading frame 104, isoform
48485
9.56
2%

CRA_a [Homo sapiens]

167
CCDC25 protein
21006
8.79
5%

167
KIAA1306 protein
120084
9.36
2%

167
unnamed protein product
112600
8.27
0%

167
annexin II cell-surface form = cytomegalovirus
2160
5.80
45%

binding protein

172
alpha-2-macroglobulin
164600
6.00
25%

172
putative
2269
9.79
38%

172
collagen, type III, alpha 1 preproprotein
139724
6.18
3%

172
dermcidin preproprotein
11391
6.08
10%

172
annexin A2, isoform CRA_c
32600
5.93
9%

172
hCG22067
30319
7.98
3%

172
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

172
hypothetical protein LOC400867
15522
10.07
4%

266
complement factor H
143694
6.21
43%

266
alpha 2 macroglobulin
167505
6.06
27%

266
inter-alpha-trypsin inhibitor heavy chain H2
106826
6.40
14%

precursor

266
inter-alpha (globulin) inhibitor H1
101795
6.31
15%

266
fibronectin precursor
260064
5.45
3%

266
chain B, complement component C3
114238
5.55
11%

266
dermcidin preproprotein
11391
6.08
10%

266
annexin A2 isoform 2
38808
7.57
7%

266
gelsolin isoform a precursor
86043
5.90
5%

266
hemopexin precursor
52254
6.57
7%

266
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

448
complement component C3
187046
6.02
22%

448
alpha-2-macroglobulin precursor
163175
6.00
14%

448
complement component C3b
25280
4.49
30%

448
hemopexin, isoform CRA_a
22935
6.78
7%

448
annexin A2 isoform 2
38580
7.57
7%

569
complement factor B
86819
6.55
34%

569
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
18%

569
complement protein C7 precursor
96647
6.09
10%

569
unnamed protein product
84549
7.23
11%

569
putative
2269
9.79
38%

569
Plasminogen
93263
6.89
1%

569
apg-1
95472
5.65
2%

706
Inter-alpha-trypsin inhibitor heavy chain H1
101782
6.31
17%

precursor

706
Coagulation factor XIII A chain precursor
837228
5.75
15%

(Coagulation factor XIIIa) (Protein-glutamine

gamma-glutamyltransferase A chain)

706
fibrinogen gamma chain, isoform CRA_a
38056
5.87
32%

706
putative
2269
9.79
38%

706
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
8%

706
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
2%

706
annexin A2 isoform 2
38808
7.57
14%

706
hornerin precursor
283111
10.04
1%

706
cathepsin D preproprotein
45037
6.10
15%

706
Proapolipoprotein
28944
5.45
5%

706
Coagulation factor XIII B chain precursor
77723
5.97
1%

(Protein-glutamine gamma-glutamyltransferase B

chain) (Transglutaminase B chain) (Fibrin-

stabilizing factor B subunit)

706
hemopexin precursor
52254
6.57
4%

706
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

706
coagulation factor XII
68618
7.94
1%

706
PREDICTED: similar to ribosomal protein L36
5528
10.50
21%

[Pan troglodytes]

723
chain A, structure of complement C3b
71459
6.82
21%

723
putative
2269
9.97
38%

723
complement component C4A
194337
6.65
4%

723
coagulation factor XII
68618
7.94
6%

723
annexin A2 isoform 2
38808
7.57
6%

723
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

752
inter-alpha (globulin) inhibitor H1
101795
6.31
21%

752
peptidoglycan recognition protein L precursor
68669
7.62
7%

752
Chain B, Human Complement Component C3
114238
5.55
8%

752
hemopexin, isoform CRA_d
43771
6.24
9%

752
heparin cofactor II precursor
57233
6.41
2%

760
Chain B, Human Complement Component C3
112869
5.55
47%

760
inter-alpha (globulin) inhibitor H1
101339
6.31
25%

760
Inter-alpha-trypsin inhibitor heavy chain H1
10326
6.31
24%

precursor (ITI heavy chain H1) (Inter-alpha-

inhibitor heavy chain 1) (Inter-alpha-trypsin

inhibitor complex component III) (Serum-derived

hyaluronan-associated protein) (SHAP)

760
Chain A, Crystal Structure Of Native Heparin
54925
6.26
32%

Cofactor Ii

760
peptidoglycan recognition protein L precursor
67927
7.62
17%

760
extracellular matrix protein 1 isoform 1 precursor
60665
6.25
22%

760
complement component 4 binding protein, alpha
66989
7.15
13%

chain precursor

760
glucosamine (N-acetyl)-6-sulfatase precursor
62042
8.60
17%

760
hemopexin precursor
51512
6.57
14%

760
fibrinogen gamma chain
49450
5.61
10%

760
histidine-rich glycoprotein precursor
59541
7.09
7%

760
Dopamine beta-hydroxylase precursor (Dopamine
67570
5.09
9%

beta-monooxygenase)

760
gp180-carboxypeptidase D-like enzyme
152819
5.70
3%

760
Alpha 2 macroglobulin variant
164030
6.00
5%

760
Regucalcin
33231
5.89
12%

760
annexin A2 isoform 2
38580
7.57
9%

760
complement 8 alpha subunit
65111
6.21
9%

760
glutathione transferase M3
26671
5.37
4%

760
unnamed protein product
69250
5.92
6%

760
gelsolin isoform a precursor
85644
5.90
1%

760
hypothetical protein
35102
7.31
8%

760
hCG22067
29692
7.98
6%

760
cAMP-specific phosphodiesterase PDE4D5
84375
5.03
2%

766
inter-alpha (globulin) inhibitor H1
101795
6.31
25%

766
inter-alpha-trypsin inhibitor
101782
6.31
23%

766
complement component C3
188585
6.02
22%

766
extracellular matrix protein (precursor)
62262
6.25
29%

766
alpha-2-macroglobulin precursor
164600
6.00
9%

766
complement component 4 binding protein
69042
7.15
16%

(precursor)

766
dopamine beta-hydroxylase precursor
68425
5.90
16%

766
gp180-carboxypeptidase D-like enzyme
153903
5.70
3%

766
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
10%

766
histidine-rich glycoprotein precursor
60510
7.09
12%

766
annexin A2 isoform 2
38808
7.57
9%

766
hemopexin precursor
52254
6.57
13%

766
fibrinogen gamma chain
50077
5.61
7%

766
heparin cofactor II precursor
57233
6.41
3%

766
peptidoglycan recognition protein L precursor
68669
7.62
5%

766
regucalcin
33802
5.89
5%

766
glucocerebrosidase precursor
57798
7.03
3%

766
dermcidin preproprotein
11391
6.08
10%

766
unnamed protein
71246
5.92
4%

766
ASC-1 complex subunit P200
220646
7.23
0%

766
lumican
38717
6.16
5%

766
plasminogen
93263
6.89
1%

766
filaggrin 2
249296
8.45
0%

766
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

766
CCDC25
21006
8.79
5%

797
complement component C3
188585
6.02
19%

797
chain A, crystal structure of native heparin
55096
6.26
41%

cofactor Ii

797
complement component 4 binding protein
69042
7.15
32%

797
hemopexin precursor
52254
6.75
42%

797
gelsolin isoform a precursor
86043
5.90
8%

797
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
5%

797
peptidoglycan recognition protein L precursor
68669
7.62
14%

797
putative
2269
9.78
38%

797
complement C4B precursor
189599
7.39
1%

797
extracellular matrix protein 1 isoform 1 precursor
62262
6.26
6%

[Homo sapiens]

797
histidine-rich glycoprotein precursor
60510
7.09
6%

797
alpha-2-macroglobulin precursor
164600
6.00
3%

797
ectonucleotide pyrophosphatase/phosphodiesterase
54745
5.94
2%

5 (putative function)

797
hornerin
48797
9.71
3%

797
Plasminogen
93263
6.89
1%

797
microcephalin
42749
7.65
12%

797
immunoglobulin heavy chain variable region
12944
8.63
12%

797
dimethylarginine dimethylaminohydrolase 1
31444
5.53
3%

797
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

797
hypothetical protein LOC400867
15522
10.07
4%

797
cardiotrophin-like cytokine factor 1
25388
8.68
3%

802
Chain B, Structure Of Complement C3b: Insights
104912
5.18
37%

Into Complement Activation And Regulation

802
peptidoglycan recognition protein L precursor
68669
7.62
12%

802
hemopexin precursor
52254
6.57
20%

802
complement component 4 binding protein, alpha
69042
7.15
7%

chain precursor

802
Chain A, Crystal Structure Of Native Heparin
55096
6.26
13%

Cofactor Ii

802
putative
2269
9.79
38%

803
Chain B, Structure Of Complement C3b: Insights
104912
5.18
36%

Into Complement Activation And Regulation

803
complement component 4 binding protein, alpha
69042
7.15
30%

chain precursor

803
Chain A, Crystal Structure Of Native Heparin
55096
6.26
32%

Cofactor Ii

803
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

803
hemopexin precursor
52254
6.57
18%

803
peptidoglycan recognition protein L precursor
68669
7.62
4%

803
putative [Homo sapiens]
2269
9.79
38%

803
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
3%

803
unnamed protein product
71246
5.92
1%

803
cystic fibrosis transmembrane conductance
169036
8.91
0%

regulator

813
peptidoglycan recognition protein L precursor
68669
7.62
8%

813
unnamed protein product
60273
6.13
12%

813
Putative
2269
9.79
38%

813
Chain A, Crystal Structure Of Native Heparin
55096
6.26
13%

Cofactor Ii

813
hemopexin precursor
52254
6.57
12%

813
complement component 3 precursor
188569
6.02
3%

813
hypothetical protein LOC400867
15522
10.07
4%

813
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

818
DEP domain containing 1, isoform
84786
8.71
0%

818
Putative
2269
9.79
38%

818
Mitochondrial ribosomal protein L30
18678
10.10
5%

822
alpha-1-B-glycoprotein
52479
5.65
35%

822
Chain B, Structure of Complement C3b: . . .
104912
5.18
25%

822
Chain A, Gelatinase A (full length)
71842
5.20
20%

822
C9 complement protein
64399
5.49
14%

822
hemopexin precursor
52254
6.57
16%

822
histidine-rich glycoprotein precursor
60510
7.09
9%

822
complement component 5 variant
124357
8.43
3%

822
Lumican
38717
6.16
8%

822
alpha-2-antiplasmin precursor
54536
5.71
10%

822
complement C4B precursor
189599
7.39
2%

822
vitamin K-dependent protein S precursor
77127
5.48
2%

822
ASPIC
71448
4.98
1%

823
complement component 4 binding protein, alpha
69042
7.15
28%

chain precursor

823
complement component 3 precursor
188569
6.02
11%

823
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
7%

823
peptidoglycan recognition protein L precursor
68669
7.62
8%

823
Putative
2269
9.79
38%

823
extracellular matrix protein 1 isoform 1 precursor
62262
6.25
4%

823
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

823
hemopexin precursor
52254
6.57
11%

823
annexin A2 isoform 2
38808
7.57
6%

823
trypsin inhibitor
107103
6.58
2%

823
dermcidin preproprotein
11391
6.08
10%

824
complement component 4 binding protein, alpha
66989
7.15
33%

chain precursor

824
complement component 3 precursor
187030
6.02
13%

824
N-acetylmuramoyl-L_alanine amidase precursor
62178
7.25
18%

824
inter-alpha-trypsin inhibitor
93402
6.02
3%

824
alpha-2-macroglobulin precursor
163175
6.00
6%

824
annexin A2 isoform 2
385800
7.57
10%

824
glucocerebrosidase precursor
57399
7.03
6%

824
hemopexin precursor
51512
6.57
10%

824
complement component C3b - human (fragments)
25280
4.49
10%

824
complement protein C7 precursor
93453
6.09
2%

824
filaggrin 2
247928
8.45
1%

869
chain A, Structure of Complement C3b
71459
6.82
65%

869
putative
2269
9.79
38%

869
DEP domain containing 1, isoform CRA_c
84786
8.71
0%

869
KIAA1481
150746
6.77
1%

956
hemopexin precursor
52254
6.57
22%

956
alpha-2-macroglobulin precursor
164600
6.00
9%

956
kallistatin
48696
7.33
13%

956
annexin A2 isoform 2
38808
7.57
12%

956
Putative
2269
9.97
38%

956
filaggrin 2
249269
8.45
0%

956
dermcidin preproprotein
11391
6.08
10%

956
alpha-fibrinogen precursor
70223
8.26
2%

956
fibronectin precursor
260064
5.45
2%

956
phospholipase D3 isoform 2
49196
6.00
2%

956
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
3%

956
Synaptonemal complex protein 1 (SCP-1)
114626
5.85
2%

956
immunoglobulin heavy chain variable region
12944
8.63
12%

956
PREDICTED: similar to mucin 19
712778
4.82
0%

967
Chain B, Structure of Complement C3b
103886
5.18
26%

967
hemopexin precursor
51512
6.57
12%

967
complement component 8
65121
6.07
9%

967
alpha-2-antiplasmin precursor
54194
5.71
4%

967
complement C8-beta propeptide
62008
8.24
3%

967
Ceruloplasmin
97637
5.29
5%

967
Regucalcin
33231
5.89
5%

967
Chain I, Crystal Structure of Antithrombin-Iii
48409
5.72
9%

967
trypsin inhibitor
106647
6.58
1%

967
gelsolin isoform a precursor
85644
5.90
1%

967
complement C4B precursor
188230
7.39
1%

967
hyaluron binding protein 2
62630
6.09
1%

967
afamin precursor
69024
5.64
2%

967
alpha-2-macroglobulin precursor
163175
6.00
1%

967
lipopolysaccharide binding protein precursor
52912
6.23
3%

967
annexin A2 isoform 2
38580
7.57
9%

967
unnamed protein product
66412
5.62
8%

967
alpha 2-plasmin inhibitor, alpha 2-PI {N-terminal,
2064
4.53
63%

form A} [human, plasma, Peptide Partial, 19 aa]

967
fibrinogen
49450
5.61
2%

967
hCG22067
29692
7.98
6%

967
beta-2-glycoprotein
38273
8.34
2%

1400
putative
2269
9.79
38%

1400
complement component C3
188585
6.02
1%

1400
Serum paraoxonase/arylesterase 1 (PON 1)
39895
5.08
6%

(Serum aryldialkylphosphatase 1) (A-esterase 1)

(Aromatic esterase 1) (K-45)

1400
dermcidin preproprotein
11391
6.08
10%

1400
hypothetical protein LOC400867
15522
10.07
4%

1400
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
3%

1400
PREDICTED: hypothetical protein
26918
11.95
2%

1400
PREDICTED: similar to ribosomal protein L36
5528
10.50
21%

[Pan troglodytes]

1400
Rho guanine nucleotide exchange factor (GEF) 17
223645
5.90
0%

1417
Serum paraoxonase/arylesterase 1 (PON 1)
66170
5.08
22%

(Serum aryldialkylphosphatase 1) (A-esterase 1)

(Aromatic esterase 1) (K-45)

1417
Putative
2269
9.79
38%

1417
complement C4B precursor
189599
7.39
3%

1417
apolipoprotein A-IV precursor
45353
5.33
9%

1417
mutant beta-actin (beta′-actin)
42128
5.22
12%

1417
complement component C3
188585
6.02
1%

1417
small proline-rich protein
8676
9.07
12%

1417
Plasminogen
93263
6.89
1%

1417
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

1417
coiled-coil domain containing 96
62958
4.92
1%

1417
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

27
alpha-1-antitrypsin
46848
5.43
25%

27
alpha-2-macroglobulin precursor
164,600
6
9%

27
dermcidin preproprotein
11391
6.08
1%

27
megakaryocyte stimulating factor
152195
9.53
1%

27
cAMP-specific phosphodiesterase
84945
5.03
1%

76
fibronectin precursor
260064
5.45
7%

76
Chain B, Structure of Complement C3b
104912
5.18
12%

76
Chain A, Thyroxine-Binding Globulin Complex
42680
5.69
17%

With Throxine

76
filaggrin
249296
8.45
0%

76
C9 complement protein
64399
5.49
3%

76
afamin
70963
5.64
6%

76
Chain, Intact Recombined Alpha-1-Antitrypsin
44322
5.43
16%

Mutant Phe 51 to Leu

76
C4A3
58960
5.67
5%

76
lipoprotein, Lp(a)
134467
5.77
1%

76
hemopexin
52254
6.57
4%

76
plasminogen
93263
6.89
1%

76
Chain A, Hemoglobulin Thionville Alpha Chain
15446
7.82
12%

Mutant

76
Chain A, Hr1b Domain from Prk1
9054
9.77
11%

93
Chain B, Crystal Structure of S-Nitroso-Nitrosyl
15922
6.81
23%

Human Hemoglobin

93
alpha-1-antitrypsin
46848
5.43
12%

93
megakaryocyte stimulating factor
152195
9.53
1%

124
kininogen 1
48936
6.29
31%

124
fibronectin precursor
260064
5.45
4%

124
unnamed protein, coagulation factor II precursor
70723
5.53
7%

206 (—)
alpha-1-antichymotrypsin
48834
5.79
9%

206 (—)
alpha-1-antitrypsin
13859
7.93
21%

206 (—)
aggrecan core protein precursor
251979
4.1
0%

206 (—)
plasminogen
93263
6.89
1%

206 (—)
creatine kinase M
43247
6.63
3%

206 (—)
secretoglobin, family 3A
10269
6.71
9%

210
alpha-2-macroglobulin
167505
6.06
23%

210
complement component C3
188585
6.02
11%

210
complement factor H
143694
6.21
6%

210
hemopexin precursor
52254
6.57
8%

210
annexin A2
38808
7.57
3%

246
alpha 2 macroglobulin
167505
6.06
15%

246
complement factor H
143694
6.21
21%

246
complement component C3
188585
6.02
4%

255
macroglobulin alpha2
162072
5.95
17%

255
complement factor H
143694
6.21
15%

265
cAMP-specific phosphodiesterase
2735857
6.93
4%

292
alpha-2-macroglobulin precursor
164600
6
19%

292
complement factor H
143694
6.21
19%

292
trypsin inhibitor
107103
6.58
8%

292
inter-alpha-trypsin heavy chain H1 precursor
101782
6.31
9%

292
gelsolin isoform a precursor
86043
5.9
1%

292
cAMP-specific phosphodiesterase
84945
5.03
4%

372
alpha 2 macroglobulin
167505
6.06
17%

372
complement factor H isoform a precursor
143654
6.23
4%

372
gelsolin isoform a precursor
86043
5.9
6%

372
hemopexin precursor
52254
6.57
4%

384
ceruloplasmin
116197
5.43
14%

384
inter-alpha-trypsin inhibitor heavy chain H4
103489
6.51
16%

precursor

384
phosphatidylinositol-glycan-specific
92943
5.91
12%

phospholipase D1 precursor

384
complement factor H isoform a precursor
143654
6.23
2%

384
alpha-2-macroglobulin precursor
164600
6
3%

385
phosphatidylinositol-glycan-specific
92943
5.91
18%

phospholipase D1 precursor

385
ceruloplasmin
116197
5.43
11%

385
inter-alpha-trypsin inhibitor family heavy chain-
103536
6.64
8%

related protein

385
alpha-2-macroglobulin precursor
164600
6
3%

385
kininogen
48936
6.29
6%

385
complement C4B
189599
7.39
3%

385
complement component C3
188585
6.02
1%

393
ceruloplasmin
116197
5.43
11%

393
inter-alpha-trypsin inhibitor heavy chain H4
103489
6.51
17%

precursor

393
phosphatidylinositol-glycan-specific
92943
5.91
7%

phospholipase D1 precursor

393
alpha-2-macroglobulin precursor
164600
6
2%

393
annexin A2 isoform 2
38808
7.57
6%

393
complement component C3
188585
6.02
1%

393
factor H
143710
6.28
1%

394
inter-alpha-trypsin inhibitor heavy chain H4
103489
6.51
16%

precursor

394
ceruloplasmin
116197
5.43
18%

394
hornerin
48797
9.71
6%

394
cAMP-specific phosphodiesterase
84945
5.03
2%

394
factor H
143710
6.28
0%

394
creatine kinase M
43247
6.63
3%

408
glycosylphosphatidylinositol specific phosphatase
93899
5.96
13%

D1

408
ceruloplasmin
116197
5.43
5%

408
brain-expressed protein BEX1
38717
6.31
12%

408
lumican
38717
6.16
2%

408
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
5%

477
alpha-2-macroglobulin precursor
163175
6
22%

477
complement component C6 precursor peptide
104718
6.39
22%

477
complement factor B
85450
6.55
11%

477
inter-alpha-trypsin inhibitor family heavy chain-
103321
6.51
2%

related protein

477
ceruloplasmin
115398
5.43
4%

477
annexin A2 isoform 2
38580
7.57
7%

481 (—)
pre-pro-alpha (I) collagen
138827
5.66
10%

495
inter-alpha-trypsin inhibitor family heavy chain-
103321
6.51
20%

related protein

495
ceruloplasmin
115398
5.43
14%

495
complement component C3
187046
6.02
10%

495
macroglobulin alpha2
160704
5.95
11%

495
complement C4B precursor
188230
7.39
5%

495
factor H
139034
6.28
6%

495
SERPINF2 protein
54559
5.87
11%

495
gp-180-carboxypeptidase D-like enzyme
152819
5.7
5%

495
oxidized protein hydrolase
81201
5.29
2%

495
complement component C6 precursor peptide
104718
6.39
9%

496
inter-alpha-trypsin inhibitor family heavy chain-
103321
6.51
23%

related protein

496
Chain B, Human Complement Component C3
112869
5.55
18%

496
alpha-2-macroglobulin precursor
163175
6
13%

496
ceruloplasmin
97637
5.29
11%

496
complement C4B precursor
188230
7.39
7%

496
complement factor H
139019
6.21
11%

496
complement component C3b
25280
4.49
23%

496
pregnancy-zone protein
163733
5.97
6%

644 ?
fibulin-1 isoform D precursor
77223
5.11
23%

644
inter-alpha-trypsin inhibitor family heavy chain-
103321
6.51
18%

related protein

644
plasminogen
90496
7.04
15%

644
complement factor B
85450
6.55
15%

644
HGF activator, preproprotein
70602
6.99
14%

644
lumican
38375
6.16
26%

644
complement component C3
187046
6.02
3%

644
inter-alpha (globulin) inhibitor H1
99357
6.59
5%

644
aggrecan core protein precursor
250040
4.1
1%

644
complement protein C7 precursor
93453
6.09
2%

644
alpha-2-macroglobulin precursor
163175
6
7%

644
fibrinogen gamma chain
49450
5.61
4%

644
serpin peptidase inhibitor, clade G
21826
6.06
10%

644
trypsin inhibitor
106647
6.58
5%

644
histidine-rich glycoprotein precursor
59541
7.09
4%

746
trypsin inhibitor
107103
6.58
8%

746
unnamed protein (coagulation factor II precursor)
70723
5.64
17%

746
afamin precursor
70963
5.64
16%

746
Vitamin K-dependent
77127
5.48
13%

746
complement component 1, s subcomponent
78174
4.86
15%

746
inter-alpha-trypsin inhibitor
99401
5.61
9%

746
ASPIC
71448
4.98
6%

746
lumican
38717
6.16
21%

746
inter-alpha (globulin) inhibitor H4
101521
6.21
8%

746
gelsolin isoform a precursor
86043
5.9
6%

746
phospholipid transfer protein isoform a precursor
54933
6.53
6%

746
lysosomal membrane glycoprotein-2
45374
5.47
1%

746
alpha-1-B-glycoprotein
52479
5.65
6%

746
creatine kinase M
43247
6.63
3%

746
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

805
complement component 3 precursor
188569
6.02
13%

805
plasma kallikrein precursor
73433
8.6
17%

805
annexin A2 isoform 2
38808
7.57
24%

805
complement C4B precursor
189599
7.39
3%

805
gelsolin
52511
5.21
6%

805
Chain, Annexin I
35246
7.77
9%

840
inter-alpha-trypsin inhibitor heavy chain H1
101782
6.31
11%

precursor

840
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
16%

840
cystic fibrosis antigen (unnamed protein)
10988
9.19
31%

840
alpha 2 macroglobulin
167505
6.06
4%

840
beta-globin
19204
6.28
17%

840
annexin A2 isoform
38808
7.57
6%

840
phospholipase D3 isoform 2
49196
6
8%

840
Chain A, Crystal Structure of Human Galectin-7
14992
7
14%

In Complex With Galactosamine

840
ezrin (p81) (cytovillin)(Villin-2)
69470
5.94
7%

840
actin, alpha 1 skeletal muscle
32370
5.26
5%

840
SCC antigen
44564
6.35
6%

840
histidine-rich glycoprotein precursor
60510
7.09
1%

840
S100 Calcium binding protein A9
13291
5.71
17%

840
hemopexin
13452
6.7
9%

849
inter-alpha-trypsin inhibitor
101782
6.31
12%

849
fibrinogen gamma
46823
5.54
25%

849
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
9%

849
extracellular matrix protein 1 isoform
62262
6.25
4%

849
coagulation factor XIII A chain precursor
83728
5.75
7%

849
alpha 2 macroglobulin
167505
6.06
4%

849
Chain B, Structure of Complement C3b
104912
5.18
95

849
annexin A2 isoform 2
38808
7.57
9%

849
beta-globin
19204
6.28
7%

849
hemopexin
52254
6.57
4%

849
peptidoglycan recognition protein L precursor
68699
7.62
2%

849
complement component 4 binding protein
69052
7.62
2%

849
plasminogen
93263
6.89
1%

849
cAMP-specific phosphodiesterase
84945
5.03
1%

856
inter-alpha-trypsin inhibitor heavy chain H1
101782
6.31
13%

precursor

856
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
11%

856
fibrinogen gamma chain
50077
5.61
13%

856
macroglobulin alpha2
162072
5.95
6%

856
Coagulation factor XIII A chain precursor
83728
5.75
8%

856
Chain B, T-To-T (High) Quaternary Transitions . . .
15954
6.79
36%

856
annexin A2 isoform
38808
7.57
13%

856
phospholipase D3
49196
6
2%

856
glucocerebrosidase precursor
57798
7.03
4%

856
histidine-rich glycoprotein precursor
60510
7.09
3%

856
complement component C3
188585
6.02
1%

856
hemopexin
13452
6.7
9%

864
inter-alpha-trypsin inhibitor heavy chain H1
101782
6.31
9%

precursor

864
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
12%

864
Ig mu chain precursor
69208
5.82
13%

864
alpha 2 macroglobulin
167505
6.06
3%

864
Chain B, T-To-T (High) . . .
15975
6.75
23%

864
annexin A2 isoform 2
38808
7.57
8%

864
complement component C3
188585
6.02
1%

864
complement factor B
86819
6.55
2%

864
phospholipase D3 isoform 2
49196
6
2%

864
hemopexin
13452
6.7
9%

864
moesin
67892
6.08
4%

864
alpha-2-antiplasmin precursor
54536
5.71
4%

962
complement 9
61728
5.42
31%

962
Chain B, Structure of Complement C3b
104912
5.18
24%

962
complement C5 precursor
189923
6.11
7%

962
alpha-2-antiplasmin precursor
54536
5.71
20%

962
Chain A, Antithrombin Iii
49350
5.95
19%

962
lumican
38717
6.16
19%

962
kininogen
48936
6.29
20%

962
complement C4B precursor
189599
7.39
3%

962
ceruloplasmin
116197
5.43
4%

962
complement component 1
54192
6.96
12%

962
hemopexin precursor
52254
6.57
9%

962
alpha 2-plasmin inhibitor
2064
4.53
63%

962
thyroxine-binding globulin precursor
46637
5.87
5%

962
thrombin inhibitor
42901
5.33
2%

962
creatine kinase M
43247
6.63
3%

973
complement 9
61728
5.42
32%

973
Chain A, antithrombin Iii
49350
5.95
35%

973
alpha-2-antiplasmin precursor
54536
5.71
14%

973
complement component C3
188585
6.02
11%

973
ceruloplasmin
116197
5.43
6%

973
complement component 5 variant
124357
8.43
9%

973
kinninogen 1
48936
6.29
14%

973
complement C4B precursor
189599
7.39
3%

973
thrombin inhibitor
42901
5.33
7%

973
L-plastin
70815
5.2
12%

973
complement component 1
54192
6.75
2%

973
angiotensinogen
53407
5.78
2%

973
alpha 2-plasmin inhibitor
2064
4.53
63%

973
alpha-1-B-glycoprotein
52479
5.65
5%

973
serine (or cysteine) proteinase inhibitor
43004
5.61
5%

973
hemopexin precursor
52254
6.57
10%

973
lumican
38717
6.16
12%

973
proapolipoprotein
28944
5.45
5%

973
phospholipase D3 isoform 2
49196
6
2%

973
hyaluronan binding protein 2
64740
6.09
1%

973
cAMP-specific phosphodiesterase
84945
5.03
5%

1472
complement component C4A
194337
6.65
5%

1472
complement component C3
188585
6.02
4%

1472
hemopexin precursor
52254
6.57
18%

1472
apolipoprotein A-IV precursor
45353
5.33
21%

1472
annexin A2 isoform 2
38808
7.57
6%

1472
serum paraoxonase/arylesterase
39895
5.08
14%

1472
preprohaptoglobulin
38941
6.13
9%

1472
beta actin
42052
5.29
13%

1472
COMP
85403
4.34
1%

1472
alpha-1-acid glycoprotein 1 precursor
21433
5.09
4%

1472
Zn-alpha2-glycoprotein
34942
5.71
3%

1472
serpin peptidase inhibitor, clade I
46287
5.01
4%

1472
thrombospondin-4
108415
4.44
1%

1472
coiled-coil domain containing 96
62958
4.92
1%

1472
Chain B, Cathepsin
26457
5.31
2%

1472
desmoglein-1 precursor
114670
4.9
1%

1472
follistatin-like 1 precursor
36103
5.39
3%

1498
complement factor H-related protein 1 precursor
38777
7.75
29%

1498
Chain B, alpha-Ferrous-Carbonmonoxy
15971
6.81
43%

1498
Chain A, Crystal Structure of Lipid-Free human
28061
5.27
35%

Apolipoprotein A-I

1498
alpha-fibrinogen precursor
70223
8.26
9%

1498
annexin A2 isoform 2
38808
7.57
10%

1498
lactoferrin (unnamed protein)
80242
8.5
2%

1498
phospholipase D3 isoform 2
49146
6
2%

1498
Chain B, Cathepsin D
26457
5.31
7%

1498
complement C4B precursor
189599
7.39
6%

1498
glutathione transferase M3
27127
5.37
4%

1498
Chain E, Structure of human transferrin receptor-
39476
6.41
5%

transferrin complex

1498
complement component C3
188585
6.02
0%

1498
plasminogen
93263
6.89
2%

1498
neuropolypeptide h3
21027
7.42
13%

1611
complement factor H-related 1
38766
7.38
35%

1611
annexin A2 isoform 2
38808
7.57
22%

1611
Chain B, alpha-Ferrous-Carbonmonoxy
15971
6.81
40%

1611
phospholipase D3 isoform 2
49196
6
2%

1611
proapolipoprotein
28944
5.45
25%

1611
Chain B, Cathepsin D
26457
5.31
7%

1611
cAMP-specific phosphodiesterase
84945
5.03
2%

1611
DF4
10966
10.3
5%

1867
complex-forming glycoprotein HC
20592
5.84
17%

1867
dermcidin preproprotein
11391
6.08
10%

1867
protein disulfide isomerase-related protein
46512
4.95
2%

1867
complement factor B
86819
6.55
0%

1867
albumin, isoform CRA_a
25732
6.45
3%

1867
thyroid receptor interactor
45785
7.7
8%

1867
cAMP-specific phosphodiesterase
84945
5.03
1%

1956
annexin A2, isoform CRA_c
32600
5.93
24%

1956
Chain, Carbonic Anhydrase Form B
28903
6.44
11%

1956
Chain B, Alpha-Ferrous-Carbonmonoxy, . . .
15971
6.81
23%

1956
complement Factor H-related Protein 2
28706
6.52
18%

1956
UCC1 protein (mammalian ependymin-related
20162
5.03
6%

protein 1)

1956
Chain B, Cathepsin D
26457
5.31
4%

1956
RNA polymerase transcriptional regulation
28505
8.91
2%

mediator

1956
serum albumin (unnamed protein)
71246
5.92
2%

1956
cathepsin F
38244
6.54
2%

1956
cAMP-specific phosphodiesterase
84945
5.03
1%

2062
dermcidin preproprotein
11391
6.08
10%

2062
glutathione S-transferase
25847
6.9
13%

2062
mutant beta-globin
12635
5.9
20%

2062
proapolipoprotein
28944
5.45
9%

2062
liprin-beta2
88864
6.29
0%

2062
HSPC336 (apolipoprotein M)
21220
6.48
8%

2062
cAMP-specific phosphodiesterase
84945
5.03
1%

2175
annexin A2 isoform 2
38808
7.57
6%

2175
glutathione transferase M3
27127
5.37
4%

2175
regucalcin
33802
5.89
3%

2175
Chain A, Human Aspartylglucosaminidase
17552
4.82
4%

2175
serum albumin (unnamed protein)
71246
5.92
1%

2175
cAMP-specific phosphodiesterase
84945
5.03
1%

2175
polymerase (DNA directed)
64070
7.96
1%

2205
glia maturation factor, beta
16874
5.19
34%

2205
serum albumin (unnamed protein)
71246
5.92
3%

2205
plasminogen
93263
6.89
2%

2205
nuclear distribution gene C homolog
38276
5.27
9%

2205
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

2205
glia maturation factor, gamma
16961
5.18
18%

2205
dermcidin preproprotein
11391
6.08
10%

1787
Chain, Human Annexin V with Proline
36041
4.94
26%

Substitution by Thioproline

1787
annexin A2 isoform 2
38808
7.57
10%

1787
cathepsin Z precursor
34544
6.7
3%

1787
complex-forming glycoprotein HC
20592
5.84
7%

1787
apolipoproprotein J precursor
49342
6.27
1%

1787
apolipoprotein D
28317
5.14
4%

1787
dermcidin preproprotein
11391
6.08
10%

1787
bromodomain adjacent to zinc finger domain 2B
222440
5.95
0%

1694
apolipoprotein J precursor
49342
6.27
14%

1694
apolipoprotein D
28317
5.14
4%

1694
COMP
855403
4.34
2%

1694
annexin A2 isoform 2
38808
7.57
2%

1694
V-set and immunoglobulin domain containing 4
44529
5.93
2%

1694
prepro-C3b/C4B
68120
7.72
1%

1694
creatine kinase M
43247
6.63
1%

1694
cAMP-specific phosphodiesterase
84945
5.03
1%

1694
regucalcin
33802
5.89
9%

1687
prepro-C3b/C4B
68120
7.72
4%

1687
regucalcin
33802
5.89
12%

1687
apolipprotein J precursor
49342
6.27
11%

1687
annexin A2 isoform 2
38808
7.57
7%

1687
ectonucleotide pyrophosphatase/phosphodiesterase
54745
5.94
1%

1687
apolipoprotein E
36302
5.65
2%

1687
Vitamin D-binding protein precursor
54526
5.4
2%

1687
dermcidin preproprotein
11391
6.08
10%

1687
plasminogen
93263
6.89
2%

1687
protein C
41122
6.41
3%

1228
alpha-2 macroglobulin precursor
164600
6
6%

1228
alpha-2-antiplasmin precursor
54536
5.71
2%

1228
annexin A2 isoform 2
38808
7.57
6%

1228
phospholipase D3 isoform 2
49196
6
2%

1228
prepro-C3b/C4B
68120
7.72
7%

1228
complement component C3
188585
6.02
2%

1228
beta globin chain
11537
5.9
40%

1228
prolylcarboxypeptidase isoform 1 preproprotein
56277
6.75
3%

1228
beta-fibrinogen precursor
55545
8.31
4%

1228
Rho guanine nucleotide exchange factor
223645
5.9
0%

1228
cAMP-specific phosphodiesterase
84945
5.03
2%

1228
MEN1 protein
64077
6.19
2%

243
ceruloplasmin
98321
5.29
8%

243
factor H
143710
6.28
3%

243
Vitamin D-binding protein precursor
54526
5.4
6%

243
trypsin inhibitor
107103
6.58
1%

243
complement component C3
188585
6.02
2%

243
Chain I, Crystal Structure of P13 Alanine Variant
49276
6.13
8%

of Antithrombin

243
complement C4B precursor
189599
7.39
4%

243
cAMP-specific phosphodiesterase
84945
5.03
1%

TABLE 3

44
fibronectin precursor, complement component C3, alpha-2-macroglobulin

precursor

82
Chain B, Structure of Complement C3b

109
factor H, fibronectin precursor

126
fibronectin 1 isoform 3 preproprotein, alpha-2-macroglobulin precursor,

164
macroglobulin alpha 2

184
alpha-2-macroglobulin

191
alpha-2-macroglobulin, complement component C3

205
no protein matches criteria

216
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

244
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

252
alpha 2 macroglobulin, complement factor H, complement component C3

267
inter-alpha-trypsin inhibitor, Human Factor H, fibronectin precursor, inter-alpha-

trypsin inhibitor, C-terminal

295
complement factor H, alpha 2 macroglobulin, trypsin inhibitor, inter-alpha-trypsin

inhibitor

352
complement factor H, alpha 2 macroglobulin, inter-alpha-trypsin inhibitor, trypsin

inhibitor, complement component C3

392
Ceruloplasmin, phosphatidylinositol-glycan-specific phospholipase D1

396
afamin precursor, ceruloplasmin, inter-alpha-trypsin inhibitor

469
complement component 6, isoform CRA_b

509
inter-alpha-trypsin inhibitor heavy chain-related protein, ceruloplasmin, Chain B,

Structure of Complement C3b

510
ceruloplasmin (ferroxidase), Chain A, Crystal Structure of human Galectin-7

512
ceruloplasmin (ferroxidase), inter-alpha-trypsin inhibitor family heavy chain-

related protein

547
serum albumin, inter-alpha-trypsin inhibitor family heavy chain-related protein

533
COMP, ceruloplasmin

554
inter-alpha-trypsin inhibitor family heavy chain-related protein

555
ALB protein, gelsolin isoform a precursor

561
serum albumin, trypsin inhibitor, complement component C3

567
Chain B, Human complement component C3

568
complement component C3, complement factor B, gelsolin isoform precursor

655
Ceruloplasmin (ferroxidase), fibulin-1 isoform D precursor, hypothetical protein

(inter-alpha-globulin inhibitor H4), valosin-containing protein, Vitamin D-binding

protein precursor

677
unnamed protein (complement component 2 precursor), annexin A2, complement

factor B

701
Annexin A2 isoform 2

703
inter-alpha-trypsin inhibitor family heavy chain-related protein, ceruloplasmin

(ferroxidase)

704
hornerin precursor

712
complement component 1, s subcomponent, ASPIC, afamin precursor, Vitamin

K-dependent protein

729
plasma kallikrein precursor, S100 calcium-binding protein A9, Protein S100-A7

(psoriasin)

744
gelsolin isoform a precursor

745
gelsolin isoform a precursor

748
gelsolin isoform a precursor, coagulation factor XIII, Chain b, Alpha-Ferrous-

Carbonmonoxy

763
afamin precursor, coagulation factor II precursor, insulin-like growth factor

binding protein, acid labile, histidine-rich glycoprotein precursor, phospholipid

transfer protein isoform a precursor, antithrombin III

764
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII B chain,

gelsolin isoform a precursor

765
ASPIC, coagulation factor II precursor (unnamed protein), vitronectin (unnamed

protein), histidine-rich glycoprotein precursor, biotinidase precursor

766
afamin precursor, insulin-like growth factor binding protein, acid labile subunit,

coagulation factor II precursor, alpha-1-B-glycoprotein, thrombin inhibitor, C9

complement protein

770
Coagulation factor XIII B chain precursor

776
insulin-like growth factor binding protein, hemopexin precursor

818
vanin 1 precursor, biotinidase precursor, vitronectin (unnamed protein), ASPIC

825
extracellular matrix protein 1 isoform precursor, hemopexin precursor, histidine-

rich glycoprotein, dopamine beta-hydroxylase precursor, peptidoglycan

recognition protein L precursor

827
Chain A, Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma

chain, hemopexin precursor

833
Extracellular matrix protein1 isoform 1 precursor, inter-alpha (globulin) inhibitor

H1, isoform CRA_b, hemopexin precursor

844
alpha-1-B-glycoprotein, alpha-2-antiplasmin precursor, complement component 1,

vitronectin precursor (unnamed protein), Vitamin K-dependent protein S

precursor, ASPIC

846
Vitamin K-dependent protein S precursor,

Chain B, Human Complement Component C3, coagulation factor (unnamed

protein), complement 9, GRP78, afamin precursor

TABLE 4

Proteins Differentially Expressed Between Healthy vs. LOA (12 sample and 18 sample)

2D

Master#
Protein
Mass
pI
Coverage

22
ceruloplasmin
116197
5.43
16%

22
complement component C3
188585
6.02
5%

22
Putative
2269
9.79
38%

22
Fibronectin precursor (FN) (Cold-insoluble globulin) (CIG)
266034
5.45
4%

22
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
3%

22
Hornerin
48797
9.71
3%

22
complement C4B precursor
189599
7.39
3%

22
mutant beta-actin (beta′-actin).2
42128
5.22
4%

22
Chain A, Crystallographic Analysis Of The Human Vitamin
52780
5.17
10%

D Binding Protein

22
dermcidin preproprotein
11391
6.08
10%

22
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

22
hCG22067
30319
7.98
3%

22
proapolipoprotein
28944
5.45
9%

22
hypothetical protein LOC400867
15522
10.07
4%

22
Chain I, Crystal Structure Of P13 Alanine Variant Of
49276
6.13
8%

Antithrombin

22
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
4%

29
chain A . . . uncleaved alpha-1-antitrypsin
44307
5.35
55%

29
cancer-associated SCM-recognition immunedefense-
46864
8.48
51%

suppressing and serine protease-protecting peptide, CRISPP

peptide

29
Putative
2269
9.79
38%

76
hypothetical protein
272166
5.30
16%

76
Chain A, Crystallographic Analysis Of The Human Vitamin
51183
5.17
53%

D Binding Protein

76
Chain B, Structure Of Complement C3b: Insights Into
103886
5.18
24%

Complement Activation And Regulation

76
ceruloplasmin
115398
5.43
15%

76
inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-
76914
5.72
9%

sensitive glycoprotein) variant

76
complement C4B precursor
188230
7.39
3%

76
afamin precursor
69024
5.64
20%

76
Chain A, Antithrombin Iii
49008
5.95
25%

76
trypsin inhibitor
106647
6.58
6%

76
alpha-2-antiplasmin precursor
54194
5.71
6%

76
C9 complement protein
62974
5.49
6%

76
hypothetical protein
272166
5.30
16%

76
Chain A, Crystallographic Analysis Of The Human Vitamin
51183
5.17
53%

D Binding Protein

76
Chain B, Structure Of Complement C3b: Insights Into
103886
5.18
24%

Complement Activation And Regulation

76
ceruloplasmin
115398
5.43
15%

76
inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-
76914
5.72
9%

sensitive glycoprotein) variant

76
complement C4B precursor
188230
7.39
3%

76
afamin precursor
69024
5.64
20%

76
Chain A, Antithrombin Iii
49008
5.95
25%

76
trypsin inhibitor
106647
6.58
6%

76
alpha-2-antiplasmin precursor
54194
5.71
6%

76
C9 complement protein
62974
5.49
6%

80
putative
2269
9.79
38%

80
unnamed protein product
47777
5.60
1%

80
Mitochondrial ribosomal protein L30
18678
10.10
5%

85
fibronectin 1 isoform 3 preproprotein
262656
5.49
26%

85
ceruloplasmin
116197
5.43
26%

85
alpha-2-macroglobulin precursor
164600
6.00
7%

85
complement component C3
188585
6.02
6%

85
putative
2269
9.79
38%

85
hemopexin
13452
6.70
9%

85
dermcidin preproprotein
11391
6.08
10%

85
complement component C4A
194337
6.65
2%

85
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
2%

(putative function)

85
PREDICTED: similar to Apolipoprotein(a) precursor
14926
5.79
7%

(Apo(a)) (Lp(a))

85
factor H
143710
6.28
1%

85
unnamed protein product
78399
8.44
1%

85
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

85
scavenger receptor class F, member 2 isoform 1
96980
8.89
1%

85
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

85
hypothetical protein LOC400867
15522
10.07
4%

96
hypothetical protein
272166
5.30
11%

96
alpha-2-macroglobulin precursor
163175
6.00
8%

96
complement component C3
187046
6.02
2%

96
dermcidin preproprotein
11277
6.08
16%

96
hornerin precursor
282199
10.04
2%

101
fibronectin 1 isoform 3 preproprotein
262656
5.49
23%

101
alpha-2-macroglobulin precursor
164600
6.00
19%

101
putative
2269
9.97
38%

101
Plasminogen
93263
6.89
1%

101
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

101
cardiotrophin-like cytokine factor 1
25388
8.68
3%

102
fibronectin 1 isoform 3 preproprotein
262656
5.49
12%

102
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
9%

102
putative
2269
9.79
38%

102
dermcidin preproprotein
11391
6.08
10%

102
filaggrin 2
249296
8.45
0%

102
profilaggrin
11043
5.36
10%

102
Chain A, Crystal Structure Of Human Galectin-7 In
14992
7.00
8%

Complex With Galactosamine

102
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

102
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
1%

103
hypothetical protein
252738
5.92
23%

103
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
17%

103
dermcidin preproprotein
11391
6.08
20%

103
filaggrin 2
249296
8.45
2%

103
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

103
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

103
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

103
hornerin
48797
9.71
6%

103
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
4%

104
fibronectin 1 isoform 3 preproprotein
262656
5.49
17%

104
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
18%

104
Putative
2269
9.79
38%

104
dermcidin preproprotein
11391
6.08
10%

104
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

111
no significant hits to report
0
0
0

112
fibronectin precursor (FN)
266034
5.45
25%

112
complement component C3
188585
6.02
8%

112
PREDICTED: similar to Apolipoprotein(a) precursor
14926
5.79
17%

112
putative
2269
9.79
38%

112
Shroom-related protein
218125
7.75
1%

112
hypothetical protein LOC400867
15522
10.07
4%

114
hypothetical protein
272166
5.30
25%

114
Alpha-2-macroglobulin precursor (Alpha-2-M)
163175
6.00
13%

114
complement component C3
187046
6.02
8%

114
complement component C3b - human (fragments)
25280
4.49
23%

114
lipoprotein, Lp(a)
130761
5.77
5%

114
filaggrin
434922
9.24
2%

122
complement component 3, isoform CRA_a
143619
8.24
11%

122
hypothetical protein
249203
5.43
10%

122
lipoprotein, Lp(a)
130761
5.77
4%

122
hornerin precursor
282199
10.04
0%

122
chain, annexin I
35018
7.77
10%

122
annexin A2 isoform 2
38580
7.57
10%

127
hypothetical protein
272166
5.30
18%

127
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
3%

protein

127
lipoprotein, Lp(a)
130761
5.77
2%

127
complement component C3
187046
6.02
5%

127
plasma protease (C1) inhibitor precursor
55147
6.09
6%

127
megakaryocyte stimulating factor
150998
9.53
5%

189
attractin-2
146159
6.65
18%

189
fibronectin precursor
260064
5.45
7%

189
afamin precursor
70963
5.64
10%

189
antithrombin III
53041
6.32
5%

189
inter-alpha-trypsin inhibitor family heavy
103549
6.51
2%

189
C9 complement protein
64399
5.49
5%

189
thrombin inhibitor
42901
5.33
2%

189
Serpin B8 (cytoplasmic antiproteinase 2)
43328
5.43
4%

189
Frzb precursor
37243
8.75
1%

189
KIAA1481
150746
6.77
0%

194
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
34%

194
putative
2269
9.79
38%

194
complement component C3
188585
6.02
2%

194
dermcidin preproprotein
11391
6.08
10%

194
factor H
66430
6.28
1%

194
hCG22067
30319
7.98
10%

194
transient receptor potential cation channel, subfamily V,
83296
6.01
1%

member 5

194
Human homologue of S. pombe nuc2+ and A. nidulans
92849
6.85
0%

bimA

194
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

215
alpha 2 macroglobulin
167505
6.06
45%

215
macroglobulin alpha 2
162072
5.95
45%

215
chain B, complement component C3
114238
5.55
41%

215
complement factor H
143654
6.23
31%

215
hypothetical protein
249992
5.77
4%

215
inter-alpha-trypsin inhibitor precursor
101782
6.31
7%

215
trypsin inhibitor
107103
6.58
7%

215
hemopexin precursor
52254
6.57
13%

215
regucalcin
33802
5.89
5%

215
annexin A2
38808
7.57
6%

215
prepro-alpha1 (I) collagen
139853
5.66
2%

215
dipeptidylpeptidase IV
1599
5.91
100%

215
gelsolin isoform a precursor
86043
5.90
3%

215
PREDICTED: similar to Hypothetical acrosin-like protease
29811
8.51
9%

215
branched chain acyltransferase precursor
53324
8.59
6%

215
FLJ00239 protein
79635
7.83
1%

215
aberrant LSLCL
33536
6.82
2%

244
complement factor H isoform a precursor
138979
6.23
24%

244
alpha-2-macroglobulin precursor
163175
6.00
13%

244
chain, x-ray crystal structure of ceruloplasmin
120009
5.41
20%

244
complement C4B precursor
188230
7.39
7%

244
ITIH1
52461
8.63
7%

244
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
6%

protein

244
hypothetical protein
246513
5.77
4%

244
S100 calcium-binding protein A8
10828
6.51
20%

244
neutrophil granule peptide HP1
3446
8.68
60%

244
chain A, crystallographic analysis of Vitamin D binding
51183
5.17
15%

protein

244
dermcidin preproprotein
11277
6.08
16%

244
inter-alpha-trypsin inhibitor heavy chain H2 precursor
106370
6.40
10%

244
Chain A, Structure Of Human Annexin A2 In The Presence
36460
8.32
5%

Of Calcium Ions

244
proapo-A-I protein
30745
5.55
4%

244
hemopexin, isoform CRA_d
43201
6.24
6%

244
complement component C3
187046
6.02
2%

244
fibrinogen alphaA
49366
5.48
5%

247
complement factor H isoform a precursor
143654
6.23
40%

247
ceruloplasmin
116197
5.43
26%

247
alpha-2-macroglobulin precursor
164600
6.00
14%

247
trypsin inhibitor
107103
6.58
16%

247
fibronectin precursor
226034
5.45
10%

247
inter-alpha (globulin) inhibitor H1
101795
6.31
11%

247
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
8%

protein

247
chain B, structure of complement C3b
104912
5.18
9%

247
regucalcin
33802
5.89
16%

247
complement C4B precursor
189599
7.39
6%

247
hemopexin precursor
52254
6.57
6%

247
chain A, antithrombin Iii
49350
5.95
9%

247
coactosin-like 1
16049
5.54
11%

247
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

247
supported by mouse EST AA538043 (NID: g2284036)
37423
9.28
2%

247
Vitamin D-binding protein precursor (DBP) (Group-specific
54526
5.40
3%

component) (Gc-globulin) (VDB)

247
PREDICTED: hypothetical protein
23723
9.91
11%

276
complement factor H isoform a precursor
143654
6.23
45%

276
inter-alpha-trypsin heavy chain H2
106826
6.40
10%

276
alpha-2-macroglobulin precursor
164600
6.00
7%

276
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
7%

276
Putative
2269
9.79
38%

292
ceruloplasmin
116197
5.43
23%

292
inter-alpha-trypsin inhibitor family heavy chain-related
103536
6.64
11%

protein

292
putative
2269
9.79
38%

292
Vitamin D-binding protein precursor (DBP) (Group-specific
54526
5.40
12%

component) (Gc-globulin) (VDB)

292
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

292
fibronectin precursor
260064
5.45
2%

292
complement C4B precursor
189599
7.39
5%

292
proapolipoprotein
28944
5.45
9%

292
mutant beta-actin (beta′-actin)
42128
5.22
2%

292
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

292
immunoglobulin lambda light chain VLJ region
11755
8.62
9%

292
annexin A2 isoform 2
38808
7.57
11%

292
coactosin-like 1
16049
5.54
5%

292
hypothetical protein LOC400867
15522
10.07
4%

305
Ceruloplasmin
116197
5.43
21%

305
putative
2269
9.79
38%

305
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
5%

protein (IHRP)

305
Vitamin D-binding protein precursor (DBP) (Group-specific
54526
5.40
6%

component) (Gc-globulin) (VDB)

305
hypothetical protein LOC400867
15522
10.07
4%

306
ceruloplasmin
116197
5.43
18%

306
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
13%

protein (IHRP)

306
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

306
Putative
2269
9.79
38%

306
factor H
143710
6.28
2%

306
fibronectin precursor
260064
5.45
1%

306
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
1%

306
unnamed protein product
112600
8.27
0%

306
complement component C3
188585
6.02
1%

306
dermcidin preproprotein
11391
6.08
10%

306
coactosin-like 1
16049
5.54
5%

306
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

327
complement conponent C3
187046
6.02
20%

327
alpha-2-macroglobulin precursor
163175
6.00
17%

327
annexin A2 isoform 2
38580
7.57
3%

327
inter-alpha (globulin) inhibitor H1, isoform CRA_c
101303
6.43
2%

327
hemopexin precursor
51512
6.57
7%

327
ceruloplasmin
97637
5.29
3%

327
putative
2212
9.79
38%

333
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
14%

proteins

333
M130 antigen
120901
5.66
10%

333
ceruloplasmin
97637
5.29
15%

333
afamin precursor
69024
5.64
19%

333
complement C4B
188230
7.39
6%

333
alpha 2 macroglobulin
166022
6.06
3%

333
C9 complement protein
62974
5.49
1%

333
dermcidin preproprotein
11277
6.08
10%

333
collagen, type VI, alpha 1 precursor
108462
5.26
6%

333
trypsin inhibitor
106647
6.58
3%

333
hypothetical protein
40328
8.67
9%

333
thrombin inhibitor
42559
5.33
9%

341
inter-alpha (globulin) inhibitor H4
101179
6.21
20%

341
ceruloplasmin
116685
5.48
18%

341
afamin precursor
69024
5.64
17%

341
alpha-2-macroglobulin precursor
163175
6.00
4%

341
M130 antigen extracellular variant
124248
5.77
4%

341
Chain, Solution Nmr Structure Of Recombinant Human
10982
5.38
12%

Cystatin A Under The Condition Of Ph 3.8 And 310k

341
hypothetical protein
40328
8.67
7%

345
ceruloplasmin
115398
5.43
15%

345
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
11%

protein

345
glycosylphosphatidylinositol specific phospholipase D1
93272
5.96
5%

345
M130 antigen extracellular variant
124248
5.77
8%

345
chain B, structure of complement C3b
103886
5.18
10%

345
alpha-2-macroglobulin precursor
163175
6.00
7%

345
hypothetical protein
240492
5.15
2%

345
Aggrecan core protein precursor (Cartilage-specific
250040
4.10
1%

proteoglycan core protein)

345
Chain A, Structure Of Human Annexin A2 In The Presence
36460
8.32
5%

Of Calcium Ions

348
ceruloplasmin
115398
5.43
16%

348
unknown
61937
6.07
19%

348
alpha-2-macroglobulin precursor
163175
6.00
7%

348
inter-alpha (globulin) inhibitor H4
101179
6.21
6%

348
serum paraoxonase/arylesterase 1
39724
5.08
11%

353
chain b, complement component C3
114238
5.55
31%

353
ceruloplasmin
116197
5.43
20%

353
phosphatidylinositol-glycan-specific phospholipase D1
92943
5.91
16%

precursor

353
alpha-2-macroglobulin precursor
164600
6.00
7%

353
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
3%

protein

353
regucalcin
33802
5.89
5%

353
complement factor H isoform a precursor
143654
6.23
1%

353
ASPIC
71448
4.98
6%

353
fibronectin precursor
260064
5.45
3%

353
alpha-1-antichymotrypsin
48834
5.79
6%

353
creatine kinase M (EC 2.7.3.2)
8024
9.90
25%

353
Chain A, Human Serum Albumin Mutant R218p
68366
5.62
3%

Complexed With Thyroxine (3,3′,5,5′-Tetraiodo-L-

Thyronine)

353
Aggrecan core protein precursor (Cartilage-specific
251979
4.10
0%

proteoglycan core protein) 1

353
C1-inhibitor
32745
8.85
2%

353
dermcidin preproprotein
11391
6.08
10%

353
alpha2-HS glycoprotein
36268
5.20
9%

353
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

357
ceruloplasmin
115398
5.43
36%

357
Chain B, Structure Of Complement C3b: Insights Into
103886
5.18
18%

Complement Activation And Regulation

357
inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-
101179
6.21
20%

sensitive glycoprotein), isoform CRA_b

357
serum vitamin D-binding protein precursor
53015
5.40
35%

357
Chain A, Antithrombin Iii
49008
5.95
31%

357
M130 antigen
120901
5.66
12%

357
afamin precursor
69024
5.64
15%

357
Alpha 2 macroglobulin variant
164030
6.00
9%

357
complement component C4A
192741
6.65
3%

357
annexin A2 isoform 2
38580
7.57
10%

357
trypsin inhibitor
106647
6.58
5%

357
Serpin B8 (Cytoplasmic antiproteinase 2) (CAP-2) (CAP2)
42758
5.43
8%

(Protease inhibitor 8)

357
C9 complement protein
62974
5.49
2%

357
COL6A1 protein
48594
5.60
8%

357
C-reactive protein
25091
6.32
3%

357
alpha-2-antiplasmin precursor
54194
5.71
4%

357
alpha-1 (III) collagen
96442
9.28
3%

357
thrombin inhibitor
42559
5.33
12%

357
immunoglobulin heavy chain variable region
12733
7.92
27%

361
Ceruloplasmin
115398
5.53
38%

361
Chain B, Structure of Complement C3b
103886
5.18
28%

361
ChainA, Antithrombin Iii
49008
5.95
23%

361
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
15%

protein

361
serum vitamin D-binding protein precursor
53015
5.40
32%

361
alpha 2 macroglobulin
166022
6.06
8%

361
M130 antigen cytoplasmic variant 2
125271
5.68
6%

361
serpin peptidase inhibitor, clade I
46116
5.08
7%

361
complement C4B precursor
188230
7.39
1%

361
PRSS3
26470
6.86
8%

361
collagen type IV
4456
12.54
30%

361
cAMP-specific phosphodiesterase
84375
5.03
1%

361
alpha-1-B-glycoprotein
51908
5.65
3%

361
Ceruloplasmin
115398
5.43
38%

361
Chain B, Structure of Complement C3b
103886
5.18
28%

361
ChainA, Antithrombin Iii
49008
5.95
23%

361
serum vitamin D-binding precursor
53015
5.40
32%

361
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
15%

protein (IHRP)

361
alpha 2 macroglobulin
166022
6.06
8%

361
M130 antigen cytoplasmic variant 2
125271
5.68
6%

361
serpin peptidase inhibitor, clade I (pancpin), member 2
46116
5.08
7%

361
complement C4B precursor
188230
7.39
1%

361
PRSS3 protein
26470
6.86
8%

361
collagen type IV: alpha1 chain
4456
12.54
30%

361
cAMP-specific phosphodiesterase PDE4D5
84375
5.03
1%

361
alpha-1-B-glycoprotein - human
51908
5.65
3%

362
ceruloplasmin
115398
5.43
33%

362
Chain A, Antithrombin
49008
5.95
28%

362
Chain B, Structure of Complement C3b
103886
5.18
19%

362
inter-alpha-trypsin family heavy chain-related protein
103321
6.51
14%

362
serum vitamin D-binding protein precursor
53015
5.40
34%

362
alpha-2-macroglobulin precursor
163175
6.00
5%

362
prepro-C3b/C4B inactivator
65725
7.72
3%

362
glutathione transferase M3
26671
5.37
8%

362
complement C4B
188230
7.39
3%

362
trypsin inhibitor
106647
6.58
1%

362
PREDICTED: similar to Hornerin
187937
9.82
1%

362
Desmoplakin
201237
6.68
2%

362
M130 antigen
120901
5.66
5%

362
unnamed protein product
40903
9.50
7%

362
small proline-rich protein 2G
8152
8.30
43%

363
ceruloplasmin
115398
5.43
26%

363
inter-alpha-trypsin inhibitor family heavy chain-related
103308
6.64
6%

protein

363
dermcidin preproprotein
11277
6.08
10%

363
small proline-rich protein 2D
7900
8.77
30%

363
filaggrin 2
247928
8.45
0%

363
desmoplakin I
331571
6.44
1%

363
nuclear transcription factor, X-box binding-like 1, isoform
69844
8.88
1%

CRA_e

370
ceruloplasmin
116197
5.43
20%

370
alpha-2-macroglobulin precursor
164600
6.00
14%

370
inter-alpha-trypsin inhibitor
103549
6.51
8%

370
complement C4B preccursor
189599
7.39
3%

370
complement component C3
188585
6.02
3%

370
factor H
143710
6.28
1%

370
fibrinogen gamma chain
50077
5.61
8%

370
annexin A2
38808
7.57
3%

374
alpha 2 macroglobulin
166022
6.06
17%

374
ceruloplasmin
115398
5.43
17%

374
hCG40889, isoform CRA_a
132000
5.98
10%

374
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
9%

protein (IHRP)

374
inter-alpha-trypsin inhibitor C-terminal
93402
6.02
5%

374
Chain B, Human Complement Component C3
112869
5.55
4%

374
hemopexin precursor
51512
6.57
8%

378
alpha 2 macroglobulin
166022
6.06
17%

378
ceruloplasmin
115398
5.43
16%

378
chain, lactoferrin
76076
8.40
18%

378
hypothetical protein
70808
5.86
10%

378
polymeric immunoglobulin receptor
83232
5.58
12%

378
protein Rei, Bence-Jones
23494
8.75
12%

378
chain, contribution of hydrogen bonds to lysozyme
14675
9.30
41%

378
deleted in malignant brain tumors 1 isoform b precursor
59167
4.69
10%

variant

378
chain A, crystal structure of human neutrophil peptide 2
3429
8.67
86%

378
unnamed protein product
64729
8.40
12%

378
Ig A1 Bur
73331
9.24
9%

378
PREDICTED: similar to Mucin-5B precursor
540248
6.12
2%

378
Annexin A2
38552
7.57
9%

378
Chain B, Structure Of Complement C3b: Insights Into
103886
5.18
6%

Complement Activation And Regulation

378
C20orf114
52434
6.67
9%

378
factor H
139034
6.28
4%

378
unnamed protein product
10931
9.19
19%

378
unnamed protein product
66412
5.62
9%

378
KRT73 protein
41985
8.42
7%

378
neutrophil elastase precursor
20748
9.30
13%

378
mutant beta-actin (beta′-actin)
41786
5.22
5%

384
hypothetical protein
164632
6.00
35%

384
ceruloplasmin
116197
5.43
11%

384
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
15%

protein

384
factor H
143710
6.28
8%

384
chain b, structure of comlement C3b
104912
5.18
9%

384
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

384
annexin A2 isoform 2
38808
7.57
6%

384
hemopexin precursor
52254
6.57
8%

384
regucalcin
33802
5.89
9%

384
fibrinogen gamma chain
50077
5.61
2%

384
cardiotrophin-like cytokine factor 1
25388
8.68
3%

384
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

389
alpha-2-macroglobulin precursor
164600
6.00
22%

389
Chain B, Complement Component C3
114238
5.55
15%

389
annexin A2 isoform 2
38808
7.57
6%

389
gelsolin isoform a precursor
86043
5.90
5%

389
complement component C6 precursor
108367
6.39
2%

389
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

389
fibronectin precursor
260064
5.45
1%

389
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

389
60/63 kda phosphoglucomutase
2279
4.03
47%

389
beta-actin
7908
6.75
29%

389
hCG22067
30319
7.98
3%

393
alpha-2-macroglobulin precursor
164600
6.00
25%

393
Chain B, Human Complement Conponent C3
114238
5.55
28%

393
inter-alpha (globulin) inhibitor H4
101521
6.21
3%

393
annexin A2 isoform 2
38808
7.57
2%

393
sex-determination protein homolog Fem1a
22632
7.22
10%

399
alpha-2-macroglobulin precursor
164600
6.00
22%

399
complement component C3
188585
6.02
7%

399
complement component C6 precursor
108367
6.39
3%

399
annexin A2 isoform 2
38808
7.57
6%

399
inter-alpha-trypsin inhibitor
93745
6.02
1%

399
dermcidin preproprotein
11391
6.08
10%

399
Chain A, Crystal Structure Analysis Of The Bb Segment Of
56816
7.16
9%

Factor B

399
gelsolin isoform a precursor
86043
5.90
3%

399
fibronectin precursor
260064
5.45
1%

399
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

399
Bruton's agammaglobulinemia tyrosine kinase
76625
8.05
4%

413
ceruloplasmin
116197
5.43
28%

413
inter-alpha-trypsin inhibitor family havey chain-related
103536
6.64
26%

protein

413
alpha-2-macroglobulin precursor
164600
6.00
21%

413
chain b, structure of complement C3b
104912
5.18
16%

413
IgG Fc binding protein
81017
5.56
5%

413
pregnancy-zone protein
165215
5.97
7%

413
complement factor H isoform a precursor
143654
6.23
5%

413
complement component C4A
194337
6.65
1%

413
regucalcin
33802
5.98
5%

413
hemopexin precursor
52254
6.57
6%

413
fibronectin precursor
260064
5.45
0%

413
fibrinogen gamma chain
50077
5.61
10%

413
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

415
alpha-2 macroglobulin precursor
163175
6.00
14%

415
complement component C6 precursor peptide
104718
6.39
22%

415
gelsolin isoform a precursor
85644
5.90
16%

415
ceruloplasmin
115398
5.43
6%

415
vinculin isoform VCL
116649
5.83
9%

415
complement component C3
187046
6.02
1%

415
annexin A2 isoform 2
38580
7.57
11%

418
complement component C6 precursor
108367
6.39
23%

418
vinculin isoform VCL
117220
5.83
24%

418
alpha-2-macroglobulin precursor
164600
6.00
17%

418
complement factor B
86819
6.55
15%

418
complement factor H isoform a precursor
143654
6.23
1%

418
complement component C3
188585
6.02
2%

418
complement protein C7 precursor
96647
6.09
7%

418
annexin A2 isoform 2
38808
7.57
2%

418
trypsin inhibitor
107103
6.58
1%

418
gelsolin isoform a precursor
86043
5.90
3%

418
chondrosarcoma-associated protein 2
65660
6.26
1%

418
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

418
epidermal growth factor receptor
90700
8.39
1%

421
complement component C6 precurosr
108367
6.39
26%

421
alpha 2 macroglobulin
167505
6.06
20%

421
complement factor B
86819
6.55
19%

421
vinculin isoform VCL
117220
5.83
15%

421
annexin A2 isoform 2
38808
7.57
9%

421
complement component C3
188585
6.02
0%

421
Plasminogen
93263
6.89
1%

421
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

429
inter-alpha (globulin) inhibitor H4
101179
6.21
19%

429
phosphatidylinositol-glycan-specific phospholipase D1
92316
5.91
13%

precursor

429
ceruloplasmin
97637
5.29
8%

429
alpha 2 macroglobulin
166022
6.06
7%

429
chain B, structure of complement C3b
103886
5.18
6%

429
serpin peptidase inhibitor, clade A
37044
6.00
12%

429
dermcidin preproprotein
11277
6.08
13%

429
PREDICTED: similar to filaggrin 2
186543
7.67
0%

429
complement component C6 precursor peptide
104718
6.39
4%

429
factor H
139034
6.28
5%

429
unnamed protein
69241
5.53
4%

429
hypothetical protein
40325
8.67
14%

429
trypsin inhibitor
106647
6.58
4%

429
inter-alpha (globulin) inhibitor H1, isoform CRA_b
99357
6.59
2%

429
Ig heavy chain V region - human
1981
9.08
5%

435
inter-alpha (globulin) inhibitor H4
101521
6.21
25%

435
chain B, structure of complement C2b
104912
5.18
13%

435
ceruloplasmin
116197
5.43
8%

435
unnamed protein product
70723
5.53
8%

435
phosphatidylinositol-glycan-specific phospholipase D1
92943
5.91
7%

precursor

435
complement component C4A
194337
6.65
1%

435
alpha 2 macroglobulin
167505
6.06
5%

435
factor H
143710
6.28
2%

435
afamin precursor
70963
5.64
6%

435
annexin A2 isoform 2
38808
7.57
6%

435
fibronectin precursor
260064
5.45
0%

435
trypsin inhibitor
107103
6.58
1%

435
dermcidin preproprotein
11391
6.08
10%

435
complement component C6 precursor peptide
108367
6.39
1%

435
lumican
38717
6.16
8%

435
Cartilage oligomeric matrix protein precursor (COMP)
85403
4.34
4%

435
Plasminogen
93263
6.89
1%

438
inter-alpha (globulen) inhibitor H4
101521
6.21
22%

438
Ceruloplasmin
180249
5.29
8%

438
complement component C3
188585
6.02
0%

438
glycosylphosphatidylinositol phospholipase D
92931
5.91
4%

438
alpha-albumin
4647
4.10
35%

445
none

447
LOST

457
inter-alpha (globulin) inhibitor H4
101521
6.21
26%

457
ceruloplasmin
116197
5.43
20%

457
Chain B, Structure of Complement C3b
104912
5.18
22%

457
Vitamin D-binding protein precursor
54526
5.40
15%

457
afamin precursor
7093
5.64
14%

457
serine proteinase inhibitor
43004
5.61
7%

457
complement component C4B
40795
5.19
12%

457
annexin A2 isoform 2
38808
7.57
6%

457
thrombin inhibitor
42901
5.33
3%

457
alpha-1-B-glycoprotein - human
52479
5.65
2%

457
thrombospondin-4
108415
4.44
3%

457
C9 complement protein
64399
5.49
1%

457
immunoglobulin G kappa chain
24212
6.18
6%

457
antithrombin III
53041
6.32
3%

457
lamin-like protein
16417
10.33
5%

466
complement component C3
188585
6.02
25%

466
alpha-2-macroglobulin precursor
164600
6.00
3%

470
complement component C3
188585
6.02
26%

470
alpha-2-macroglobulin precursor
164600
6.00
7%

470
mitochondrial ribosomal protein
18678
10.01
5%

472
inter-alpha (globulin) inhibitor H4
101521
6.21
22%

472
ceruloplasmin
116197
5.43
22%

472
Vitamin-D-binding protein precursor
54526
5.40
26%

472
Chain B, Structure of Complement C3b
104912
5.18
17%

472
afamin precursor
70963
5.64
9%

472
dermcidin prepropprotein
11391
6.08
10%

472
glutathione transferase M3
27127
5.37
4%

472
small proline-rich protein 2D
8584
8.77
30%

472
FAM124A

5.47
1%

472
antithrombin
14064
5.91
24%

472
plasminogen
93263
6.89
1%

472
complement C4B precursor
189599
7.39
1%

472
hCG22067
30319
7.98
6%

473
ceruloplasmin
116197
5.43
17%

473
inter-alpha-trypsin inhibitor
103549
6.51
13%

473
complement component C3
188585
6.02
0%

475
plasminogen
90526
6.89
25%

475
complement component 3 precursor
187030
6.02
9%

475
complement C5 precursor
188212
6.11
10%

475
poly-Ig receptor
75474
5.38
2%

475
plasminogen 1-69
7818
4.72
30%

475
annexin A2 isoform 2
38580
7.57
3%

475
TPA: Hornerin
282204
10.04
2%

476
ceruloplasmin
116197
5.43
13%

476
inter-alpha-trypsin inhibitor family heavy chain
103549
6.51
12%

476
lymphoid-rectricted membrane protein
56691
5.44
3%

477
complement factor B
86819
6.55
19%

477
putative
2269
9.79
38%

477
dermcidin preproprotein
11391
6.08
20%

477
complement protein C7 precursor
96647
6.09
4%

477
plasminogen
93233
7.04
2%

477
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
1%

477
hCG22067
30319
7.98
3%

477
unnamed protein product
84549
7.23
1%

477
filaggrin 2
249296
8.45
0%

477
PREDICTED: similar to Cyclin G-associated kinase
148776
7.67
0%

477
hCG2044987
11472
9.73
8%

481
ceruloplasmin
116197
5.43
27%

481
Inter-alpha-trypsin inhibitor heavy chain H4 precursor (ITI
103489
6.51
15%

heavy chain H4) (Inter-alpha-inhibitor heavy chain 4)

481
putative
2269
9.79
38%

481
complement component C3
188585
6.02
3%

481
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
2%

481
dermcidin preproprotein
11391
6.08
10%

481
Cartilage oligomeric matrix protein precursor (COMP)
85403
4.34
1%

481
coactosin-like 1
16049
5.54
16%

481
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

482
ceruloplasmin
116197
5.43
17%

482
mutant beta-actin
42128
5.22
22%

482
chain b, structure of complement C3b
104912
5.18
15%

482
inter-alpha-trypsin inhibitor family havey chain-related
103549
6.51
13%

protein

482
alpha-2-macroglobulin precursor
164600
6.00
5%

482
regucalcin
33802
5.89
9%

482
complement C4B precursor
189599
7.39
2%

482
ATP synthase . . .
59828
9.16
3%

482
Ca ATPase SERCA1
110654
5.06
4%

482
dermcidin preproprotein
11391
6.08
10%

482
fibrinogen gamma chain
50077
5.61
4%

482
annexin A2, isoform CRA_c
32600
5.93
9%

482
fibronectin precursor
260064
5.45
0%

482
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

482
cartilage oligomeric matrix protein precursor
85403
4.34
2%

482
Human basement membrane heparan sulfate proteoglycan
479812
6.10
0%

core protein

482
hemopexin precursor
52254
6.57
4%

482
small proline-rich protein
8676
9.07
25%

482
unnamed protein product
71246
5.92
1%

482
hypothetical protein LOC60686
59375
5.71
1%

482
cardiotrophin-like cytokine factor 1
25388
8.86
3%

482
unnamed protein product
57976
5.80
3%

482
cytochrome C oxidase II subunit
21095
4.68
3%

482
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

484
ceruloplasmin
97637
5.29
14%

484
hypothetical protein
70808
5.86
12%

484
complement component C3
187046
6.02
6%

484
alpha-2-macroglobulin precursor
163175
6.00
1%

484
Cartilage oligomeric matrix protein precursor (COMP)
82780
4.34
4%

484
inter-alpha (globulin) inhibitor H2, isoform CRA_a
106502
6.48
4%

484
complement component C4A
193541
6.79
1%

484
hypothetical protein
122035
6.20
2%

484
peptide, salivary low MW
1068
8.75
100%

484
dermcidin preproprotein
11277
6.08
19%

555
alpha-2-macroglobulin precursor
164600
6.00
15%

555
fibrinogen gamma
46823
5.54
24%

555
inter-alpha-trypsin inhibitor
93745
6.02
2%

555
putative
2269
9.97
38%

555
complement C1r subcomponent precursor
81661
5.89
2%

555
complement component C3
188585
6.02
2%

555
talin
271828
5.75
1%

555
annexin A2 isoform 2
38808
7.57
6%

555
hemopexin precursor
52254
6.57
9%

555
plasminogen
93233
7.04
4%

555
dermcidin preproprotein
11391
6.08
10%

555
complement factor B
86819
6.55
2%

555
ubiquitin
8446
6.56
12%

555
gelsolin isoform a precursor
86043
5.90
1%

555
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

555
unnamed protein product
112600
8.27
0%

583
lumican
38717
6.16
34%

583
C1-inhibitor
32745
8.85
21%

583
putative
2269
9.79
38%

583
filaggrin 2
249296
8.45
0%

583
Chain A, High Resolution Solution Nmr Structure Of
11629
4.82
26%

Mixed Disulfide Intermediate Between Mutant Human

Thioredoxin And A 13 Residue Peptide Comprising Its

Target Site In Human Nfkb

583
dermcidin preproprotein
11391
6.08
10%

583
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

583
caspase 14 precursor
27947
5.44
12%

583
SCP-1
114424
5.84
2%

583
unnamed protein product
14405
8.03
9%

583
creatine kinase M (EC 2.7.3.2)
8024
9.90
25%

583
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

584
alpha-2-macroglobulin precursor
164600
6.00
11%

584
complement component 7 precursor
96650
6.09
16%

584
complement factor B
86819
6.55
14%

584
putative
2269
9.79
38%

584
unnamed protein product
84549
7.23
0%

584
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

586
complement component 7 precursor
93457
6.09
27%

586
complement factor B
85450
6.55
26%

586
Chain A, antithrombin Iii
49008
5.95
42%

586
unnamed protein product
83180
7.23
8%

586
alpha-2-macroglobulin precursor
163175
6.00
8%

586
serpin peptidase inhibitor, clade F
57016
6.47
13%

586
PREDICTED: hypothetical protein
31731
11.91
6%

588
complement factor B
86819
6.55
35%

588
complement component 7 precursor
96650
6.09
22%

588
alpha-2-macroglobulin precursor
164600
6.00
7%

588
unnamed protein product
84549
7.23
5%

588
putative
2269
9.79
38%

588
unnamed protein product
112600
8.27
0%

588
hCG2041887
9274
9.80
11%

588
centrin
19552
4.62
7%

589
plasma protease (C1) inhibitor precursor
55375
6.09
15%

589
putative
2269
9.79
38%

589
trypsin inhibitor
107103
6.58
8%

589
lumican
38717
6.16
25%

589
complement component 1, s subcomponent
78174
4.86
8%

589
Biotinidase precursor
59760
5.50
6%

589
Inter-alpha-trypsin inhibitor heavy chain H3 precursor (ITI
99401
5.61
4%

heavy chain H3) (Inter-alpha-inhibitor heavy chain 3)

(Serum-derived hyaluronan-associated protein) (SHAP)

589
Vitamin K-dependent protein S precursor
77127
5.48
7%

589
dermcidin preproprotein
11391
6.08
10%

589
coagulation factor XII
68618
7.94
2%

589
hCG22067
30319
7.98
3%

589
cadherin-5
87288
5.19
1%

589
alpha-1-antichymotrypsin
48834
5.79
9%

589
alpha-2-macroglobulin
71321
5.47
1%

589
creatine kinase M
43247
6.63
3%

589
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

589
ceruloplasmin
98321
5.29
1%

589
PREDICTED: similar to epsilon-COP protein isoform 6
37072
5.00
3%

[Pan troglodytes]

589
CTCL tumor antigen se2-1
94014
5.37
3%

589
aggrecan 1
251979
4.10
0%

597
carboxypeptidase N precursor
61433
5.72
20%

597
plasma protease (C1) inhibitor precursor
55375
6.09
18%

597
Cartilage oligomeric matrix protein precursor (COMP)
85403
4.34
16%

597
putative
2269
9.79
38%

597
Aggrecan core protein precursor (Cartilage-specific
251979
4.10
1%

proteoglycan core protein) (CSPCP) (Chondroitin sulfate

proteoglycan core protein 1) [Contains: Aggrecan core

protein 2]

597
alpha-1-antichymotrypsin
48834
5.79
12%

597
cadherin 13 preproprotein
78694
4.80
1%

597
Lumican
38717
6.16
15%

597
dermcidin preproprotein
11391
6.08
10%

597
protein, alpha1 acid glyco
21443
5.09
4%

597
creatine kinase M
43247
6.63
1%

597
apolipoprotein D, apoD [human, plasma, Peptide, 246 aa]
28317
5.14
4%

597
CTCL tumor antigen se2-1
94014
5.37
3%

597
hCG2038603, isoform CRA_a
9461
9.76
8%

597
B-cell receptor-associated protein BAP29
28512
9.63
6%

597
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

600
plasma protease (C1) inhibitor precursor
55375
6.09
13%

600
PREDICTED: similar to Carboxypeptidase N subunit 2
61401
5.72
20%

precursor (Carboxypeptidase N polypeptide 2)

600
Cartilage oligomeric matrix protein precursor (COMP)
85403
4.34
9%

600
alpha-1-antichymotrypsin
48834
5.79
16%

600
lumican
38717
6.16
15%

600
putative
2269
9.79
38%

600
apolipoprotein D, apoD [human, plasma, Peptide, 246 aa]
28317
5.14
10%

600
Aggrecan core protein precursor (Cartilage-specific
251979
4.10
0%

proteoglycan core protein)

600
dermcidin preproprotein
11391
6.08
10%

600
cadherin 13 preproprotein
78694
4.80
2%

600
protein, alpha1 acid glyco
21443
5.09
4%

600
hCG2038603, isoform CRA_a
9461
9.76
8%

600
creatine kinase M
43247
6.63
3%

600
fibronectin precursor
260064
5.45
0%

600
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
2%

604
alpha-2-macroglobulin precursor
163175
6.00
9%

604
fibrinogen gamma
46252
5.54
22%

604
complement C1r subcomponent precursor
80122
5.89
15%

604
complement C4B precursor
188230
7.39
5%

604
ceruloplasmin
97637
5.29
3%

610
Alpha-2-macroglobulin precursor
164600
5.50
2%

610
complement component C4A
194337
6.00
13%

610
complement component C4
194216
6.65
7%

610
complement C4d
31323
6.89
7%

610
ceruloplasmin
116197
4.72
21%

610
afamin precursor
70963
5.43
10%

610
fibrinogen gamma chain
50077
5.64
17%

610
complement component C3
188585
5.61
9%

610
complement C1r subcomponent precursor
81661
6.02
1%

610
inter-alpha-trypsin inhibitor C-terminal
93745
5.89
7%

610
regucalcin
33802
6.02
4%

610
trypsin inhibitor
107103
5.89
5%

610
cardiotrophin-like cytokine factor 1
25388
6.58
6%

610
KIAA0805
150569
8.68
3%

611
complement component C4A
194337
6.65
5%

611
alpha 2 macroglobulin
167505
6.06
9%

611
inter-alpha-trypsin inhibitor
103549
6.51
5%

611
FAM124A
32947
5.47
1%

611
ceruloplasmin
98321
5.29
1%

611
L-serine dehydrase
35079
8.11
2%

611
hCG2032446
4973
10.15
18%

612
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
14%

612
complement C4B precurso
189599
7.39
6%

612
fibrinogen gamma chain
50077
5.61
8%

612
Complement C1r subcomponent precursor (Complement
81661
5.89
10%

component 1, r subcomponent)

612
putative
2269
9.79
38%

612
ceruloplasmin
98321
5.29
3%

612
DEP domain containing 1, isoform CRA_c
84786
8.71
0%

612
membrane metallo-endopeptidase-like 1
89152
5.63
2%

616
alpha-2-macroglobulin precursor
163175
6.00
19%

616
complement C4B precursor
188230
7.36
12%

616
fibrinogen gamma chain
49450
5.61
12%

616
complement C1r subcomponent precursor
80122
5.89
17%

616
ceruloplasmin
97637
5.29
10%

616
inter-alpha-trypsin C-terminal
825681
6.02
6%

616
complement component C3
187046
6.02
3%

616
regucalcin
33231
5.89
5%

616
Chain G, Gelsolin G4-G6ACTIN COMPLEX
36347
5.00
13%

616
ANXA2 protein
40503
8.41
14%

616
afamin precursor
69024
5.64
4%

616
trypsin inhibitor
106647
6.58
4%

616
hemopexin
13338
6.70
9%

616
C1-inhibitor
32688
8.85
2%

616
SMF protein
156810
7.48
1%

616
alpha-2-antiplasmin precursor
54194
5.71
2%

622
gelsolin isoform a precursor
86043
5.90
16%

622
putative
2269
9.79
38%

622
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

622
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
3%

622
annexin A2 isoform 2
38808
7.57
13%

622
dermcidin preproprotein
11391
6.08
10%

622
Chain A, Structure Of Human Trypsin Iv (Brain Trypsin)
24832
6.56
5%

622
unnamed protein product
7974
4.93
13%

622
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
2%

622
hCG2040015, isoform CRA_a
47466
6.07
1%

622
Complement C1r subcomponent precursor (Complement
81661
5.89
15%

component 1, r subcomponent)

622
potassium voltage-gated channel, shaker-related subfamily,
39547
8.81
1%

beta member 2 isoform 2

652
inter-alpha-trypsin inhibitor heavy chain H2 precursor
106826
6.40
11%

652
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
8%

protein

652
unnamed protein product
70723
5.53
18%

652
complement component 1
78174
4.86
15%

652
vitamin K-dependent protein
77127
5.48
13%

652
inter-alpha-trypsin inhibitor heavy chain H3 precursor
99401
5.61
8%

652
afamin precursor
70963
5.64
13%

652
ASPIC
71448
4.98
10%

652
phospholipid transfer protein
44989
8.69
11%

652
inter-alpha-trypsin inhibitor
93745
6.02
6%

652
putative
2269
9.79
38%

652
lumican
38717
6.16
18%

652
dermcidin preproprotein
11391
6.08
10%

652
Cartilage oligomeric matrix protein precursor (COMP)
85403
4.34
1%

652
gelsolin isoform a precursor
52511
5.21
2%

652
C1-inhibitor
32745
8.85
3%

652
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

652
coagulation factor XII
68618
7.94
2%

652
proapolipoprotein
28944
5.45
4%

652
TERF1 (TRF1)-interacting nuclear factor 2
39779
9.30
3%

653
fibrinogen gamma chain
50077
5.61
13%

653
inter-alpha-trypsin inhibitor
93745
6.02
5%

653
complement component C3
188585
6.02
1%

653
KIAA1481
150746
6.77
0%

653
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
2%

654
complement component 1
78174
4.86
14%

654
mutant beta-actin
42128
5.22
6%

654
ASPIC
71448
4.98
4%

654
lumican
38717
6.16
12%

654
complement component C3
188585
6.02
2%

654
inter-alpha-trypsin inhibitor
99401
5.61
4%

654
afamin precursor
70963
5.64
4%

654
trypsin inhibitor
107103
6.58
3%

663
plasma protease (C1) inhibitor precursor
55375
6.09
31%

663
putative
2269
9.79
38%

663
complement component C3
188585
6.02
0%

663
Aggrecan core protein precursor (Cartilage-specific
251979
4.10
1%

proteoglycan core protein)

663
protein, alpha1 acid glyco
21443
5.09
4%

663
unnamed protein product
11786
5.80
0%

663
lumican
38717
6.16
8%

663
ataxia-telangiectasia
355538
6.37
1%

663
KIAA0056
171834
7.55
2%

664
no significant hits to report
0
0.00
0%

665
gelsolin isoform a precursor
85644
5.90
37%

665
unnamed protein product
7974
5.48
34%

665
Complement C1r subcomponent precursor (Complement
80122
5.89
4%

component 1, r subcomponent)

665
fibrinogen gamma chain, isoform CRA_o
47344
5.54
10%

665
hemopexin, isoform CRA_c
28546
6.55
10%

665
Trypsin-3 precursor
32478
7.46
10%

665
dimethylglycine dehydrogenase-like protein isoform 2;
51949
6.86
9%

putative sarcosine dehydrogenase

673
Inter-alpha-trypsin inhibitor heavy chain H2 precursor (ITI
106826
6.40
18%

heavy chain H2)

673
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
15%

protein (IHRP)

673
unnamed protein product
70723
5.53
14%

673
Vitamin K-dependent protein S precursor
77127
5.48
9%

673
afamin precursor
70963
5.64
7%

673
putative
2269
9.79
38%

673
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
1011782
6.31
3%

heavy chain H1)

673
caspase 14 precursor
27947
5.44
4%

673
KIAA1481 protein
150746
6.77
0%

673
Plasminogen
93263
6.89
7%

673
creatine kinase M
43247
6.63
3%

673
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

676
afamin
69024
5.64
41%

676
inter-alpha-trypsin inhibitor heavy chain H2 precursor
106370
6.40
20%

676
inter-alpha (globulin) inhibitor H1
101339
6.31
10%

676
fibulin
61552
4.85
9%

676
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
5%

protein (IHRP)

676
complement C4B precursor
188230
7.39
7%

676
unnamed protein product
69241
5.53
10%

676
complement component C
187046
6.02
2%

676
ceruloplasmin
97637
5.29
7%

676
alpha-1-B-glycoprotein
69990
5.65
8%

676
unnamed protein product
78029
8.51
2%

676
lacritin
14237
5.45
16%

676
regucalcin
33231
5.89
5%

676
C9 complement protein
62974
5.49
5%

676
lipophilin
9891
9.41
10%

676
lipocalin 1 precursor
19238
5.39
6%

676
secretoglobin, family 2A, member 1
10876
5.48
43%

676
Complement C5 precursor [Contains: Complement C5 beta
188212
6.11
0%

chain; Complement C5 alpha chain; C5a anaphylatoxin;

Complement C5 alpha′ chain]

676
proapolipoprotein
28944
5.45
4%

676
hemopexin
13338
6.70
9%

676
alpha-2-antiplasmin precursor
54194
5.71
7%

676
regulator of G-protein signaling 9
76917
9.42
8%

676
lumican
38375
6.16
14%

679
inter-alpha-trypsin inhibitor heavy chain H2 precursor
106826
6.40
22%

679
coagulation factor II precursor
71475
5.64
35%

679
afamin precursor
70963
5.64
30%

679
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
11%

protein

679
heat shock protein 90 kDa alpha (cytosolic)
98622
5.09
18%

679
lumican
38717
6.16
28%

679
vitamin k-dependent protein S precursor
77127
5.48
11%

679
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
6%

679
fibulin-1A
65487
4.85
5%

679
coagulation factor XII
68618
7.94
4%

679
regucalcin
33802
5.89
5%

679
complement component C3
188585
6.02
2%

679
phospholipid transfer protein isoform a precursor
54933
6.53
6%

679
C4B3
47973
5.78
7%

679
ASPIC
71448
4.98
1%

679
ceruloplasmin
98321
5.29
1%

679
gelsolin isoform a precursor
86043
5.90
1%

679
unnamed protein product
79911
8.51
1%

679
cardiotrophin-like cytokine factor 1
25388
8.68
3%

688
afamin precursor
69024
5.64
44%

688
Inter-alpha-trypsin inhibitor heavy chain H2 precursor
106370
6.40
21%

688
inter-alpha (globulin) inhibitor H1
101339
6.31
10%

688
fibulin-1A
61552
4.85
12%

688
unnamed protein product
69241
5.53
13%

688
Chain B, Structure Of Complement C3b
103886
5.18
8%

688
Ceruloplasmin
97637
5.29
5%

688
Vitamin K-dependent protein S precursor
75074
5.48
6%

688
lumican
38375
6.16
18%

688
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
5%

protein (IHRP)

688
complement component C4A
192741
6.65
2%

688
precursor of P100 serine protease of Ra-reactive factor
79210
5.42
4%

688
serpin peptidase inhibitor, clade I (pancpin), member 2
46116
5.08
5%

688
butyrylcholinesterase precursor
68374
7.12
3%

688
annexin A2 isoform 2
38580
7.57
2%

688
phospholipid transfer protein isoform a precursor
54705
6.53
5%

688
alpha-1-B-glycoprotein - human
51908
5.65
2%

688
gelsolin isoform a precursor
85644
5.90
2%

688
90 kDa heat shock protein
83242
4.97
3%

688
dermcidin preproprotein
11277
6.08
10%

688
cAMP-specific phosphodiesterase PDE4D5
84375
5.03
1%

695
fibrinogen gamma chain
50077
5.54
26%

695
Chain B, Human Complement Component C3
114238
5.50
10%

695
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
6%

695
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
2%

695
hemopexin
13452
6.70
9%

695
alpha-2-macroglobulin precursor
164600
6.00
1%

695
complement C1r subcomponent precursor
81661
5.89
6%

697
trypsin inhibitor
107103
6.58
13%

697
afamin precursor
70963
5.64
27%

697
complement component C3
188585
6.02
8%

697
Chain A, Crystal Structure Of Lipid-Free Human
28061
5.27
39%

Apolipoprotein A-I

697
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
101782
6.31
9%

heavy chain H1) (Inter-alpha-inhibitor heavy chain 1)

(Inter-alpha-trypsin inhibitor complex component III)

(Serum-derived hyaluronan-associated protein) (SHAP)

697
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
9%

protein (IHRP)

697
putative
2269
9.79
38%

697
insulin-like growth factor binding protein, acid labile
66735
6.33
14%

subunit

697
antithrombin III
53041
6.32
9%

697
ceruloplasmin
116197
5.43
4%

697
dermcidin preproprotein
11391
6.08
10%

697
complement C4B precursor
189599
7.39
2%

697
lumican
38717
6.16
10%

697
hemopexin precursor
52254
6.57
4%

697
coagulation factor XII
68618
7.94
2%

697
Chain L, Alpha-Thrombin (E.C.3.4.21.5) Complex With
4145
4.65
27%

Hirulog 3

697
Vitamin D-binding protein precursor (DBP) (Group-specific
54526
5.40
4%

component) (Gc-globulin) (VDB)

697
C9 complement protein
64399
5.49
2%

697
Pyruvate dehydrogenase E1 component subunit beta,
39536
6.20
4%

mitochondrial precursor (PDHE1-B)

697
Iron-binding acute phase protein (88 kDa Eales protein)
2956
4.22
28%

697
unnamed protein product
79911
8.51
1%

697
alpha-1-B-glycoprotein - human
52479
5.65
2%

700
inter-alpha (globulin) inhibitor H2
105150
6.56
23%

700
complement component 3 precursor
187030
6.02
17%

700
afamin precursor
69024
5.64
28%

700
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
17%

protein (IHRP)

700
unnamed protein product
69241
5.53
16%

700
poly-Ig receptor
75474
5.38
6%

700
complement component C3b - human (fragments)
25280
4.49
28%

700
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
101326
6.31
11%

heavy chain H1)

700
Chain A, Crystal Structure Of Lipid-Free Human
28061
5.27
38%

Apolipoprotein A-I

700
coagulation factor XII
66337
7.94
7%

700
ceruloplasmin
115398
5.43
6%

700
insulin-like growth factor binding protein, acid labile
65994
6.33
6%

subunit

700
complement C4B precursor
188230
7.39
6%

700
Chain A, Apo-Human Serum Transferrin (Non-
74643
6.58
8%

Glycosylated)

700
alpha-1-B-glycoprotein - human
51908
5.65
11%

700
serum vitamin D-binding protein precursor
53015
5.40
22%

700
hemopexin precursor
51512
6.57
12%

700
histidine-rich glycoprotein precursor
59541
7.09
4%

703
inter-alpha globulin inhibitor H2 polypeptide
106397
6.40
21%

703
afamin precursor
69024
5.64
21%

703
inter-alpha-trypsin inhibitor C-terminal
93402
6.02
7%

703
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
6%

protein (IHRP)

703
Chain A, Crystal Structure Of Lipid-Free Human
28061
5.27
49%

Apolipoprotein A-I

703
ceruloplasmin
97637
5.29
8%

703
Chain B, Structure Of Complement C3b: Insights Into
103886
5.18
8%

Complement Activation And Regulation

703
unnamed protein product
69241
5.53
8%

703
hemopexin, isoform CRA_a
22935
6.78
9%

703
Chain A, Apo-Human Serum Transferrin (Non-
74643
6.58
7%

Glycosylated)

703
insulin-like growth factor binding protein, acid labile
65994
6.33
7%

subunit

703
fibrinogen gamma chain
49450
5.61
6%

703
glucosamine (N-acetyl)-6-sulfatase precursor
62042
8.60
2%

703
complement component C4A
193541
6.79
3%

703
PREDICTED: similar to Prostate, ovary, testis expressed
117315
5.66
3%

protein on chromosome 2

703
phospholipid transfer protein isoform a precursor
54705
6.53
6%

709
ASPIC
71448
4.98
17%

709
inter-alpha (globulin) inhibitor H3
100072
5.53
6%

709
putative
2269
9.79
38%

709
Chain H, Alpha-Thrombin (E.C.3.4.21.5) Complex With
30118
8.88
4%

Hirulog 3

709
coagulation factor XII
68618
7.94
5%

709
phospholipid transfer protein isoform a precursor
54933
6.53
3%

709
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
2%

protein (IHRP)

709
lumican
38717
6.16
21%

709
trypsin inhibitor
107103
6.58
2%

709
afamin precursor
70963
5.64
6%

709
dermcidin preproprotein
11391
6.08
10%

709
biotinidase precursor
62006
5.81
3%

709
filaggrin 2
249296
8.45
0%

709
creatine kinase M
43247
6.63
3%

709
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

709
Interferon-induced guanylate-binding protein 2 (GTP-
67654
5.54
4%

binding protein 2)

710
inter-alpha (globulin) inhibitor H1
101795
6.31
23%

710
inter-alpha-trypsin inhibitor heavy chain H2
106826
6.40
19%

710
insulin-like growth factor binding protein
66735
6.33
20%

710
coagulation factor XII
68618
7.94
8%

710
hemopexin precursor
52254
6.57
13%

710
unnamed protein product
70723
5.53
9%

710
histidine-rich glycoprotein precursor
60510
7.09
9%

710
ceruloplasmin
98321
5.29
7%

710
complement C4B precursor
189599
7.39
2%

710
complement component C3
179665
6.02
1%

710
lumican
38717
6.16
5%

710
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
4%

721
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
101782
6.31
19%

heavy chain H1)

721
fibrinogen gamma
46823
5.54
29%

721
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
8%

721
putative
62320
9.79
38%

721
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
3%

721
annexin A2 isoform 2
38808
7.57
6%

721
DEP domain containing 1, isoform CRA_c
84786
8.71
0%

721
histidine-rich glycoprotein precursor
84768
7.09
1%

721
lymphoid-restricted membrane protein
56691
5.44
1%

722
inter-alpha-trypsin inhibitor heavy chain H1 precursor
101782
6.31
21%

722
fibrinogen gamma chain
50077
5.61
29%

722
gamma-actin
26147
5.65
18%

722
Na/K-ATPase alpha 1 subunit isoform a proprotein
114135
5.33
10%

722
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
8%

722
annexin A2
38808
7.57
6%

722
alpha-2-macroglobulin precursor
164600
6.00
2%

722
hornerin
48797
9.71
6%

722
heat shock protein gp96 precursor
90309
4.73
6%

722
trypsin (EC 3.4.21.4) III precursor - human
27329
5.95
9%

722
coagulation factor XII
68618
7.94
7%

722
sodium/potassium-transporting ATPase alpha-4 chain
115119
6.23
4%

722
filaggrin 2
249296
8.45
0%

722
alpha 1 actin precursor
42366
5.23
6%

722
4F2 heavy chain antigen
58155
5.15
2%

722
complement component C3
188585
6.02
1%

722
histidine-rich glycoprotein precursor
60510
7.09
1%

722
ATP synthase, H transporting, mitochondrial
59828
9.16
2%

722
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

727
ASPIC
71448
4.98
33%

727
coagulation factor XII
68618
7.94
12%

727
lumican
38717
6.16
18%

727
hornerin
48797
9.71
10%

727
inter-alpha-trypsin inhibitor
103549
6.51
5%

727
inter-alpha-trypsin inhibitor heavy chain H3 precursor
99401
5.61
4%

727
unnamed protein
70723
8.27
0%

727
histidine-rich glycoprotein precursor
60510
7.09
5%

730
inter-alpha (globulin) inhibitor H1
101339
6.31
19%

730
inter-alpha-trypsin inhibitor heavy chain H2
106370
6.40
12%

730
glucosamine (N-acetyl)-6-sulfatase precursor
62042
8.60
12%

730
complement conponent C3
187046
6.02
7%

730
fibrinogen gamma chain
49450
5.61
15%

730
afamin precursor
69024
5.64
12%

730
glycoprotein V (platelet)
60921
9.73
4%

730
annexin A2 isoform 2
38580
7.57
5%

730
alpha-2-macroglobulin precursor
163175
6.00
2%

730
TPA: Hornerin
282204
10.04
2%

730
plasminogen
90526
6.89
3%

730
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
38273
8.34
4%

(Apolipoprotein H)

730
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
1%

protein (IHRP)

743
ASPIC
71448
4.98
30%

743
coagulation factor XII
68618
7.94
7%

743
inter-alpha-trypsin family heavy chain-related protein
103549
6.51
4%

743
inter-alpha-trypsin heavy chain H3 precursor
99401
5.61
7%

743
lumican
38717
6.16
16%

743
unnamed protein (vitronectin)
55106
5.55
7%

743
complement component C3
188585
6.02
0%

743
DEP domain containing 1, isoform
84786
8.71
0%

787
complement component C3
188585
6.02
16%

787
phospholipid transfer protein
44989
8.69
20%

787
hemopexin precursor
52254
6.57
14%

787
Chain I, Crystal Structure Of P13 Alanine Variant Of
49276
6.13
20%

Antithrombin

787
ceruloplasmin
98321
5.29
7%

787
alpha-1-B-glycoprotein
52479
5.65
17%

787
putative
54809
9.79
38%

787
histidine-rich glycoprotein precursor
60510
7.09
10%

787
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
1%

787
proapolipoprotein
28944
5.45
4%

787
Chain L, Alpha-Thrombin (E.C.3.4.21.5) Complex With
4145
4.65
27%

Hirulog 3

787
Chain A, Crystal Structure Of Native Heparin Cofactor Ii
55096
6.26
3%

787
JAK family protein tyrosine kinase
126761
6.64
5%

787
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

805
alpha 2 macroglobulin
166022
6.06
2%

805
anti-colorectal carcinoma heavy chain
50570
6.22
2%

805
zinc finger protein 217
115199
8.78
1%

817
Chain B, Structure Of Complement C3b: Insights Into
104912
5.18
27%

Complement Activation And Regulation

817
alpha-1-B-glycoprotein - human
52479
5.65
20%

817
complement component C3b
26135
4.49
21%

817
hemopexin precursor
52254
6.57
14%

817
Complement C5 precursor [Contains: Complement C5 beta
189923
6.11
1%

chain; Complement C5 alpha chain; C5a anaphylatoxin;

817
putative
2269
9.79
38%

817
C9 complement protein
64399
5.49
10%

817
alpha-2-antiplasmin precursor
54536
5.71
7%

817
ceruloplasmin
98321
5.29
3%

817
hyaluronan binding protein 2
64740
6.09
9%

817
dermcidin preproprotein
11391
6.08
10%

817
Chain E, Prethrombin2 (E.C.3.4.21.5) Complexed With
34245
8.32
7%

Hirugen (N-Acetylhirudin 53-64 With Sulfato-Tyr 63)

817
complement C4B precursor
189599
7.39
2%

817
collagenase type IV precursor
73279
5.20
3%

817
antithrombin III
53041
6.32
8%

817
histidine-rich glycoprotein precursor
60510
7.09
3%

817
ASPIC
71448
4.98
2%

817
alpha 2-plasmin inhibitor, alpha 2-PI {N-terminal, form A}
2064
4.53
63%

[human, plasma, Peptide Partial, 19 aa]

817
lumican
38717
6.16
2%

822
alpha-1-B-glycoprotein
52479
5.65
35%

822
Chain B, Structure of Complement C3b: . . .
104912
5.18
25%

822
Chain A, Gelatinase A (full length)
71842
5.20
20%

822
C9 complement protein
64399
5.49
14%

822
hemopexin precursor
52254
6.57
16%

822
histidine-rich glycoprotein precursor
60510
7.09
9%

822
complement component 5 variant
124357
8.43
3%

822
lumican
38717
6.16
8%

822
alpha-2-antiplasmin precursor
54536
5.71
10%

822
complement C4B precursor
189599
7.39
2%

822
vitamin K-dependent protein S precursor
77127
5.48
2%

822
ASPIC
71448
4.98
1%

825
chain B, structure of complement C3b
103886
5.18
33%

825
alpha-1-B-glycoprotein
51908
5.65
22%

825
complement component 5 variant
123274
8.43
9%

825
complement component 9
63133
5.43
27%

825
collagenase type IV precursor
72196
5.20
18%

825
hemopexin precursor
51512
6.57
16%

825
hornerin precursor
282199
10.04
5%

825
complement C4B precursor
188230
7.39
7%

825
SERPINF2 protein
54559
5.87
19%

825
ceruloplasmin
97637
5.29
4%

825
histidine-rich glycoprotein precursor
59541
7.09
6%

825
afamin precursor
69024
5.64
7%

825
ASPIC
70650
4.98
7%

825
phospholipid transfer protein isoform a precursor
54705
6.53
9%

825
hyaluronan binding protein 2
62630
6.09
8%

825
Vitamin K-dependent protein S precursor
75074
5.48
6%

825
Chain A, Antithrombin Iii
49008
5.95
15%

825
thrombin inhibitor
42559
5.33
3%

834
Chain b, structure of complement C3b
103886
5.18
34%

834
alpha-1-B-glycoprotein
51908
5.65
22%

834
complement component 8, alpha polypeptide
65121
6.07
14%

834
hemopexin precursor
51512
6.57
31%

834
complement component C4A
193541
6.79
6%

834
coagulation facotr II precursor
69992
5.64
16%

834
ceruloplasmin
97637
5.29
9%

834
hyalluronan binding protein 2
62630
6.09
11%

834
alpha-2-antiplasmin precursor
54194
5.71
10%

834
heparin cofactor II precursor
57062
6.41
13%

834
histidine-rich glycoprotein precursor
59541
7.09
7%

834
unnamed protein product
66412
5.62
9%

834
Complement C5 precursor
188212
6.11
1%

834
ASPIC
70650
4.98
5%

846
DEP domain containing 1, isoform CRA_c
84786
8.71
0%

846
putative
2269
9.79
38%

859
Chain b, Structure of Complement C3b
104912
5.18
41%

859
alpha-1-B-glycoprotein
52479
5.65
31%

859
hemopexin precursor
52254
6.57
29%

859
antithrombin III
53041
6.32
14%

859
hyaluronan binding protein 2
64740
6.09
3%

859
mutant beta-actin
42128
5.22
4%

859
complement component C4A
194337
6.65
0%

859
ceruloplasmin
98321
5.29
1%

859
histidine-rich glycoprotein precursor
60510
7.09
2%

859
hCG039828, isoform CRA_b
10319
11.25
9%

884
complement 9
61728
5.42
33%

884
alpha-2-antiplasmin precursor
54536
5.71
18%

884
Complement C5 precursor
189923
6.11
6%

884
complement component 1
54192
6.75
9%

884
PRSS3 protein
27040
6.86
8%

884
Alpha-2-macroglobulin precursor
164600
6.00
2%

884
kininogen 1
48936
6.29
19%

884
alpha 2-plasmin inhibitor
2064
4.53
63%

884
hemopexin precursor
52254
6.57
12%

884
complement component C3
188585
6.02
2%

884
lumican
38717
6.16
16%

884
Thyroxine-binding globulin precursor
46637
5.87
8%

884
dermcidin preproprotein
11391
6.08
10%

884
complement component C4A
194337
6.65
2%

884
angiotensinogen
53407
5.78
3%

884
apolipoprotein E
36302
5.65
2%

885
complement component 4 binding protein
69042
7.15
9%

885
unnamed protein (serum albumin precursor)
71246
5.92
7%

885
trypsin inhibitor
107103
6.58
3%

885
hemopexin precursor
52254
6.57
95%

885
Chain A, Trypsin (transmembrane protease)
24669
7.64
3%

886
alpha-1-antichymotrypsin precursor
45567
5.32
6%

886
putative
2269
9.79
38%

886
complement conponent C3
188585
6.02
2%

886
COMP_HUMAN
91772
4.45
6%

886
lumican
38717
6.16
10%

886
dermcidin preproprotein
11391
6.08
10%

886
tumor endothelial marker 7-related precursor
60116
5.99
1%

886
hCG22067
30319
7.89
3%

886
Plasminogen
932663
6.89
1%

886
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

887
complement 9
61728
5.42
42%

887
complement C5 precursor
189923
6.11
9%

887
alpha-2-antiplasmin precursor
54536
5.71
31%

887
alpha-1-B-glycoprotein
52479
5.65
28%

887
Chain A, antithrombin Iii
49350
5.95
24%

887
complement component C3
188585
6.02
4%

887
hemopexin, isoform CRA_d
43771
6.24
13%

887
hyaluronan binding protein 2
64740
6.09
3%

887
alpha-2-plasmin inhibitor
2064
4.53
63%

887
ceruloplasmin
116197
5.43
0%

887
Serpin B8 (cytoplasmic antiportease)
43328
5.43
2%

887
T-plastin polypeptide
64281
5.73
1%

897
hemopexin precursor
52254
6.57
52%

897
putative
2269
9.76
76%

897
DNA cytosine methyltransferase 3 alpha isoform a
103390
6.19
0%

897
unnamed protein product
112600
8.27
0%

902
complement 9
61728
5.42
38%

902
Complement C5 precursor
189923
6.11
11%

902
alpha-2-antiplasmin precursor
54536
5.71
34%

902
lumican
38717
6.16
23%

902
complement component 1
54192
6.75
10%

902
hemopexin precursor
52254
6.57
11%

902
alpha-2-plasmin inhibitor
2064
4.53
63%

902
alpha-1-B-glycoprotein
52479
5.65
3%

902
complement component C3
188585
6.02
0%

903
alpha-1-B-glycoprotein
52479
5.65
40%

903
complement 9
61728
5.42
21%

903
L-plastin
70815
5.20
26%

903
hyaluronan binding protein 2
64740
6.09
19%

903
Chain B, Structure of Complement C3b
104912
5.18
19%

903
alpha-2-antiplasmin precursor
54536
5.71
16%

903
Chain A, antithrombin Iii
49350
5.95
31%

903
hemopexin precursor
52254
6.57
24%

903
Complement C5 precursor
189923
6.11
3%

903
alpha-2 plasma inhibitor
2064
4.53
63%

903
complement component 1, r subcomponent-like precursor
54192
6.75
2%

903
complement C4B precursor
189599
7.39
7%

903
regucalcin
33802
5.89
9%

903
lipoprotein Gln I
28329
5.27
13%

903
PRSS3
27040
6.86
12%

903
ceruloplasmin
98321
5.29
2%

903
heat shock 70 kDa protein 8 isoform 1
71082
5.37
3%

903
lumican
38717
6.16
15%

903
c-AMP-specific phosphodiesterase PDE4DF
84945
5.03
1%

903
hCG40021
114560
9.58
0%

925
Kininogen 1
47871
6.29
64%

925
lumican
38375
6.16
39%

925
angiotensinogen
53122
5.78
8%

925
unnamed protein product
54308
5.55
10%

925
alpha-2-antiplasmin precursor
54194
5.71
6%

925
complement C8-beta propetide /map = ‘1p36.2-p22.1’
62008
8.24
13%

/hgml_locus_uid = ‘LE0166P’

925
dermcidin preproprotein
11277
6.08
10%

925
alpha-1-antichymotrypsin precursor
45453
5.32
11%

925
histidine-rich glycoprotein precursor
59541
7.09
4%

925
apolipoprotein J precursor
48772
6.27
4%

925
Thyroxine-binding globulin precursor (T4-binding globulin)
46295
5.87
5%

(Serpin A7)

925
alpha-2-macroglobulin
70751
5.47
5%

925
Plasminogen
90526
6.89
4%

925
small proline-rich protein
8049
9.07
25%

925
unnamed protein product
129330
4.71
2%

925
antithrombin III
52585
6.32
4%

925
ectonucleotide pyrophosphatase/phosphodiesterase 5
54631
5.94
2%

(putative function)

925
extracellular protein - human
43109
5.26
5%

925
hemopexin precursor
51512
6.57
8%

925
phosphodiesterase 4D, cAMP-specific (phosphodiesterase
24635
9.88
12%

E3 dunce homolog, Drosophila), isoform CRA_a

925
unnamed protein product
69250
5.92
5%

934
complement component 8
65121
6.21
39%

934
hemopexin precursor
51512
6.57
30%

934
serum albumin precursor
69180
5.91
31%

934
macroglobulin alpha2
160704
5.95
8%

934
leukotriene A4 hydrolase
69241
5.80
7%

934
Plasminogen
90526
6.89
4%

937
ASPIC
71448
4.98
17%

937
Inter-alpha-trypsin inhibitor heavy chain H3 precursor (ITI
99401
5.61
5%

heavy chain H3)

937
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
2%

protein (IHRP)

937
lumican
38717
6.16
21%

937
putative
2269
9.79
38%

937
coagulation factor XII
68618
7.94
25%

937
Chain H, Alpha-Thrombin (E.C.3.4.21.5) Complex With
30118
8.88
10%

Hirulog 3

937
phospholipid transfer protein isoform a precursor
54933
6.53
3%

937
trypsin inhibitor
107103
6.58
2%

937
biotinidase precursor
62006
5.81
5%

937
filaggrin 2
249296
8.45
0%

937
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
35%

937
dermcidin preproprotein
11391
6.08
10%

937
unnamed protein product
55106
5.55
6%

937
creatine kinase M (EC 2.7.3.2)
8024
6.63
3%

937
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

937
afamin precursor
70963
5.64
4%

937
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
4%

937
complement component 8, alpha polypeptide precursor
66832
6.07
24%

937
serum albumin
71316
6.05
30%

937
hemopexin precursor
52254
6.57
23%

937
macroglobulin alpha2
162072
5.95
5%

937
putative
2269
9.79
38%

937
kallistatin
486966
7.33
10%

937
annexin A2 isoform 2
38808
7.57
11%

937
dermcidin preproprotein
11391
6.08
10%

937
phosphodiesterase 4D, cAMP-specific (phosphodiesterase
24806
9.88
12%

E3 dunce homolog, Drosophila), isoform CRA_a

937
lumican
38717
6.16
7%

937
complement component C3
188585
6.02
1%

937
RNA polymerase II largest subunit
218413
7.12
0%

951
hemopexin precursor
52254
6.57
40%

951
complement component 8, polypeptide precursor
66832
6.07
16%

951
alpha-2-macroglobulin precursor
164600
6.00
4%

951
similar to human albumin, Swiss-Prot Accession Number
53416
5.69
6%

P02768

951
unnamed protein product
112600
8.27
0%

951
putative
2269
9.79
38%

951
DNA cytosine methyltransferase 3 alpha isoform a
103390
6.19
1%

951
MDN1, midasin homolog
638009
5.46
1%

959
hemopexin precursor
52254
6.57
55%

959
alloalbumin Venezia
71177
5.99
29%

959
complement component 8
66832
6.07
7%

959
chain A, complement component C2a
58977
6.62
14%

959
alpha-2-macroglobulin precursor
164600
6.00
5%

959
complement component C3
188585
6.02
7%

959
putative
2269
9.79
38%

959
Plasminogen
93263
6.89
2%

959
complement C8-beta propetide /map = ‘1p36.2-p22.1’
63605
8.24
1%

/hgml_locus_uid = ‘LE0166P’

959
meltrin-beta/ADAM 19 homologue
103606
8.62
3%

959
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

959
cardiotrophin-like cytokine factor 1
25388
8.68
3%

959
p107
122168
7.32
2%

963
beta-fibrinogen precursor
55545
8.31
20%

963
alpha-2-macroglobulin precursor
164600
6.00
8%

963
beta-2-glycoprotein precursor
39584
8.34
13%

963
hemopexin precursor
52254
6.57
8%

963
phospholipase D3 isoform 2
49196
6.00
6%

963
complement component 1
81788
5.89
10%

963
prolycarboxypeptidase
56277
6.75
3%

963
annexin A2
38808
7.57
2%

963
regucalcin
33802
5.89
5%

963
T-plastin polypeptide
64281
5.73
7%

968
hemopexin precursor
51512
6.57
46%

968
alpha 2 macroglobulin
166022
6.06
9%

968
complement component 8, alpha polypeptide precursor
65121
6.07
31%

968
serum albumin
69321
6.05
33%

968
serine (or cysteine) proteinase inhibitor, clade A (alpha-1
48511
7.33
22%

antiproteinase, antitrypsin), member 4 [

968
annexin A2 isoform 2
38580
7.57
29%

968
leukotriene A4 hydrolase
69241
5.80
8%

968
regucalcin
33231
5.86
5%

968
Collagen alpha-3(VI) chain precursor
343340
6.40
3%

968
complement component C3
187046
6.02
1%

968
phospholipase D3 isoform 1
54671
6.02
5%

968
Plasminogen
90526
6.89
2%

968
alpha-2-antiplasmin precursor
54194
5.71
5%

968
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
38273
8.34
11%

(Apolipoprotein H) (Apo-H) (B2GPI) (Beta(2)GPI)

(Activated protein C-binding protein) (APC inhibitor)

(Anticardiolipin cofactor)

968
major vault protein, isoform CRA_a
17434
10.25
10%

984
alpha-1-antichymotrypsin precursor
45567
5.32
36%

984
Corticosteroid-binding globulin precursor (CBG)
45283
5.64
18%

(Transcortin) (Serpin A6)

984
unnamed protein product
266882
4.45
2%

984
mutant beta-actin (beta′-actin)
42128
5.22
20%

984
unnamed protein product
55106
5.55
10%

984
Aggrecan core protein precursor (Cartilage-specific
251979
4.10
1%

proteoglycan core protein)

984
putative
2269
9.79
38%

984
Chain A, Crystal Structure Of Human Galectin-7 In
14992
7.00
17%

Complex With Galactosamine

984
unnamed protein product
10988
9.19
27%

984
S100 calcium-binding protein A9
13291
5.71
25%

984
kininogen 1
48936
6.29
2%

984
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

984
lumican
38717
6.16
5%

984
creatine kinase M
43247
6.63
1%

984
FLJ00154 protein
161963
5.51
2%

984
kallistatin = tissue kallikrein inhibitor {C-terminal} [human,
28
12.30
33%

Peptide Partial, 15 aa]

1018
Chain A, Antithrombin Iii
49008
5.95
58%

1018
serum vitamin D-binding protein precursor
53015
5.40
35%

1018
angiotensinogen
53122
5.78
15%

1018
complement C4B precursor
188230
7.39
7%

1018
alpha-2-antiplasmin precursor
54194
5.71
18%

1018
kininogen 1
47871
6.29
18%

1018
blood plasma glutamate carboxypeptidase precursor;
59893
8.02
8%

prostate-specific membrane antigen (PSMA)

1018
chainA, Thyroxine-Binding Globulin complex with
42452
5.69
15%

thyroxine

1018
regucalcin
33231
5.89
13%

1018
alpha 2-plasmin inhibitor, alpha 2-PI {N-terminal, form A}
2064
4.53
63%

1018
lumican
38375
6.16
16%

1018
CXCR4
40581
8.46
2%

1019
Chain A, antithrombin Iii
49350
5.95
66%

1019
putative
2269
9.79
38%

1019
angiotensinogen
53407
5.78
7%

1019
vitamin D-binding protein precursor
54526
5.40
9%

1019
alpha-2-antiplasmin precursor
54536
5.71
4%

1019
unnamed protein product
112600
8.27
0%

1019
possible protein TPRDII
205536
8.59
1%

1019
PDZ domain protein
167849
4.83
2%

1019
Ral-GDS related protein Rgr
53054
8.17
2%

1019
cardiotropin-like cytokine factor 1
25388
8.68
3%

1021
putative
2269
9.79
38%

1021
annexin A2 isoform 2
38808
7.57
14%

1021
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
2%

1021
complement component C3
188585
6.02
2%

1021
hemopexin precursor
52254
6.57
8%

1021
phospholipase D3 isoform 2
49196
6.00
2%

1021
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
2%

(Apolipoprotein H)

1021
PREDICTED: hypothetical protein LOC137392 isoform 9
38661
9.94
8%

1021
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

1021
complement 8 alpha subunit
66822
6.21
6%

1021
kallistatin
48696
7.33
2%

1021
albumin, isoform CRA_a
25732
6.45
3%

1021
hypothetical protein LOC400867
15522
10.07
4%

1021
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1055
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
4%

1055
putative
2269
9.79
38%

1055
annexin A2 isoform 2
38808
7.57
11%

1055
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
4%

(Apolipoprotein H)

1055
dermcidin preproprotein
11391
6.08
10%

1055
kallistatin
48696
7.33
4%

1055
hypothetical protein
71353
5.88
2%

1055
FUSE binding protein 2
68735
8.52
5%

1055
plasma carboxypeptidase B2 isoform a preproprotein
48982
7.61
1%

1055
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

1055
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1055
cardiotrophin-like cytokine factor 1
25388
8.68
3%

1056
Alpha 2 macroglobulin variant
164030
6.00
21%

1056
apolipoprotein H precursor
38287
8.34
30%

1056
serine (or cysteine) proteinase inhibitor
48511
7.33
21%

1056
plasma carboxypeptidase B2 isoform a preproprotein
48411
7.61
23%

1056
hypothetical protein
40328
8.67
20%

1056
selenoprotein P
42758
7.87
12%

1056
regucalcin
33231
5.89
9%

1056
neuropolypeptide h3 [human, brain, Peptide, 186 aa]
20913
7.42
22%

1056
phospholipase D3 isoform 2
48740
6.00
2%

1056
Complement C1r subcomponent precursor
80122
5.89
3%

1056
small proline-rich protein 2D
7900
8.77
48%

1056
dermcidin preproprotein
11277
6.08
10%

1056
hypothetical protein
69357
5.88
3%

1056
FUSE binding protein 2
68393
8.52
6%

1056
alpha-2-antiplasmin precursor
54194
5.71
4%

1056
PREDICTED: similar to Cyclin G-associated kinase
146324
9.19
3%

1056
hypothetical protein
130088
5.93
1%

1063
putative
2269
9.79
38%

1063
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
3%

1063
annexin A2 isoform 2
38808
7.57
6%

1063
complement component C3
188585
6.02
1%

1063
dermcidin preproprotein
11391
6.08
10%

1063
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
11391
8.34
2%

(Apolipoprotein H)

1063
Complement C1r subcomponent precursor (Complement
81661
5.89
1%

component 1, r subcomponent)

1063
phospholipase D3 isoform 2
49196
6.00
3%

1063
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

1063
unnamed protein product
71246
5.92
3%

1076
alpha-2-macroglobulin precursor
164600
6.00
18%

1076
beta-2-glycoprotein 1 precursor
39584
8.34
7%

1076
kallistatin
48696
7.33
1%

1089
alpha-2-macroglobulin precursor
163175
6.00
10%

1089
serine proteinase inhibitor
48511
7.33
4%

1089
beta-2-glycoprotein 1 precursor
38273
8.34
18%

1089
hemopexin precursor
51512
6.57
2%

1089
anti-colorectal carcinoma heavy chain
50570
6.22
2%

1094
apolipoprotein H precursor
39598
8.34
33%

1094
alpha-2-macroglobulin precursor
164600
6.00
5%

1094
cardiotropin-like cytokine factor 1
25388
8.68
3%

1097
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
8%

1097
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
5%

(Apolipoprotein H)

1097
putative
2269
9.79
38%

1097
phospholipase D3 isoform 2
49196
6.00
3%

1097
DEP domain containing 1, isoform CRA_c
84786
8.71
0%

1110
chain B, crystal structure of fibrinogen
38081
5.84
24%

1110
beta-2-glycoprotein 1 precursor
39584
8.34
24%

1110
alpha 2 macroglobulin
167505
6.06
4%

1110
putative
2269
9.79
38%

1110
dermcidin preproprotein
11391
6.08
10%

1110
annexin A2 isoform 2
38808
7.57
8%

1110
phospholipase D3 isoform 2
49196
6.00
3%

1110
hemopexin precursor
52254
6.57
4%

1110
far upstream element (FUSE) binding protein 1, isoform
69188
8.18
7%

CRA_c

1110
Man9-mannosidase
71004
5.92
4%

1110
unnamed protein product
112600
8.27
2%

1110
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

1110
immunoglobulin lambda light chain VLJ region
11755
8.62
9%

1110
hypothetical protein LOC400867
15522
10.07
4%

1110
Rho guanine nucleotide exchange factor (GEF) 17
223645
5.90
1%

1110
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1125
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
9%

1125
beta-fibrinogen precursor
55545
8.31
30%

1125
peptide, salivary low MW
1068
8.75
100%

1125
kallistatin
48696
7.33
6%

1125
putative
2269
9.79
38%

1125
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
6%

(Apolipoprotein H)

1125
Uncharacterized protein C6orf170
14555
6.37
1%

1125
histatin 3
6145
10.09
13%

1125
peptide, salivary low MW
971
8.75
100%

1125
type XVIII collagen
154430
5.45
0%

1125
prolylcarboxypeptidase isoform 1 preproprotein
56277
6.75
1%

1125
Ras-GRF2
6046
11.71
16%

1125
hypothetical protein LOC400867
15522
10.07
4%

1126
Chain A, Crystal Structure of Human Beta-2-glycoprotein-I
37499
8.37
58%

1126
alpha-2-macroglobulin precursor
164600
6.00
6%

1126
phospholipase D3 isoform 2
49196
6.00
5%

1126
myc far upstream element-binding protein
67664
7.21
1%

1126
coronin-like protein
51722
6.12
3%

1126
Chain B, Crystal Structure of Fibrinogen
38081
5.84
6%

1128
alpha-2-macroglobulin precursor
164600
6.00
3%

1128
prolylcarboxypeptidase
56277
6.75
3%

1128
hemopexin precursor
52254
6.57
8%

1128
beta-2-glycoprotein
39584
8.34
2%

1128
complement C1r subcomponent precursor
81661
5.89
7%

1128
serine dehydrase, isoform CRA_b
45379
9.14
7%

1139
beta-2-glycoprotein 1 precursor
38273
8.34
23%

1139
alpha-1-B-glycoprotein
51908
5.65
18%

1139
chain B, structure of complement C3b
103886
5.18
16%

1139
fibrinogen beta chain, isoform CRA_g
50370
8.63
8%

1139
filaggrin 2
247928
8.45
1%

1139
alpha-amylase
33074
7.56
7%

1139
hypothetical protein
40328
8.67
7%

1139
aldehyde dehydrogenase I
36718
7.12
5%

1139
Alpha-2-macroglobulin precursor (Alpha-2-M)
163175
6.00
4%

1139
PREDICTED: similar to membrane-associated ring finger
78153
9.27
4%

(C3HC4) 4

1139
arginase (EC 3.5.3.1)
34712
7.10
6%

1140
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
9%

1140
kallistatin
48696
7.33
27%

1140
beta-2-glycoprotein 1 precursor
39584
8.34
17%

1140
beta-fibrinogen precursor
55545
8.31
10%

1140
trypsin inhibitor
107103
6.58
5%

1140
putative
2269
9.79
38%

1140
annexin A2 isoform 2
38808
7.57
10%

1140
phospholipase D3 isoform 2
49196
6.00
5%

1140
dermcidin preproprotein
11391
6.08
10%

1140
alpha-fibrinogen precursor
70223
8.26
3%

1140
prolylcarboxypeptidase isoform 1 preproprotein
56277
6.75
3%

1140
Plasminogen
93263
6.89
2%

1140
unnamed protein product
112600
8.27
0%

1140
unnamed protein product
33844
6.67
3%

1140
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1140
PREDICTED: similar to ribosomal protein L36 [Pan
5528
10.50
21%

troglodytes]

1140
small proline-rich protein
8676
9.07
25%

1140
Rho guanine nucleotide exchange factor (GEF) 17
223645
5.90
1%

1146
beta-fibrinogen precursor
55545
8.31
51%

1146
apolipoprotein H precursor
39598
8.34
31%

1146
phospholipase D3 isoform 2
49196
6.00
8%

1146
putative
2269
9.79
38%

1146
plasma serine protease inhibitor precursor
45886
9.38
2%

1146
alpha-2-macroglobulin precursor
164600
6.00
4%

1146
unnamed protein product
112600
8.27
0%

1146
golgi membrane protein GP73
45346
4.91
1%

1147
alpha 2 macroglobulin
167505
6.06
18%

1147
apolipoprotein H precursor
39598
8.34
22%

1147
fibrinogen beta chain, isoform CRA-d
52749
8.33
45%

1147
phospholipase D3 isoform 2
49196
6.00
6%

1147
annexin A2
32600
5.93
5%

1147
PRSS3
27040
6.89
8%

1147
plasminogen
93263
6.89
2%

1147
ankyrin-3
482387
6.12
0%

1147
cAMP-specific phosphodiesterase 4D
23995
9.75
15%

1147
solute carrierfamily 4, sodium bicarbonate cotransporter,
110494
8.62
0%

member 5, isoform CRA_b

1156
fibrinogen beta chain
52759
8.33
57%

1156
apolipoprotein H precursor
39598
8.34
37%

1156
annexin A2
38808
7.57
24%

1156
fibrinogen alphaA
49708
5.48
8%

1156
alpha-figrinogen precursor
70223
8.26
10%

1156
adenylyl cyclase-associated protein
51926
8.07
13%

1156
phospholipase D3 isoform 2
49196
6.00
2%

1156
trypsinogen IV b-form
28611
5.86
8%

1156
myc far upstream element-binding protein
67664
7.21
3%

1156
plasminogen
93263
6.89
5%

1156
solute carrier family 4
110494
8.62
0%

1156
chain b, human complement component C3
114238
5.55
3%

1156
Rho guanine nucleotide exchange factor 17
223645
5.90
0%

1158
fibrinogen beta chain, isoform CRA_d
52131
8.33
63%

1158
beta-2-glycoprotein 1 precursor
38273
8.34
19%

1158
annexin A2 isoform 2
38580
7.57
21%

1158
fibrinogen alphaA
49366
5.48
6%

1158
phospholipase D3 isoform 2
48740
6.00
2%

1158
plasma serine protease inhibitor precursor
45772
9.38
2%

1158
Plasminogen
90526
6.89
2%

1158
B-cell translocation gene 2
17405
8.29
4%

1158
unnamed protein product
55188
9.10
4%

1169
fibrin beta
51358
7.95
61%

1169
fibrinogen beta chain, isoform CRA_b
28040
8.16
34%

1169
fibrinogen alphaA
49708
5.48
8%

1169
annexin A2 isoform 2
38808
7.57
14%

1169
alpha-fibrinogen precursor
70223
8.26
9%

1169
putative
2269
9.79
38%

1169
plasma serine protease inhibitor precursor
45886
9.38
5%

1169
dermcidin preproprotein
11391
6.08
10%

1169
phospholipase D3 isoform 2
49196
6.00
2%

1169
adenylyl cyclase-associated protein
51926
8.07
2%

1169
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
4%

(Apolipoprotein H)

1169
beta-fibrinogen
7107
10.12
13%

1169
Plasminogen
93263
6.89
2%

1169
acid sphingomyelinase-like phosphodiesterase
20848
6.33
3%

1169
IGHG1 protein
52367
7.88
4%

1169
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
7%

1174
serum vitamin D-binding protein precursor
54612
5.40
64%

1174
complement component C4A
194337
6.65
2%

1174
alpha-2-antiplasmin precursor
54536
5.71
5%

1174
putative
2269
9.79
38%

1174
serpin B8
43328
5.43
4%

1174
antithrombin III
53041
6.32
2%

1174
alpha 2-plasmin inhibitor
2064
4.53
63%

1174
lumican
38717
6.16
2%

1174
unnamed protein product
112600
8.27
0%

1174
unnamed protein product
16391
6.21
5%

1187
chain B, structure of complement C3b
104912
5.18
30%

1187
alpha-1-antitrypsin
46848
5.43
32%

1187
chain I, P14-fluorescein-N135q-S380c-antithrombin-Iii
49388
5.95
39%

1187
hemopexin precursor
52254
6.57
32%

1187
alpha-1-B-glycoprotein
52479
5.65
16%

1187
ceruloplasmin
98321
5.29
12%

1187
phospholipid transfer protein
44989
8.69
20%

1187
putative
2269
9.97
38%

1187
afamin precursor
70963
5.64
3%

1187
unnamed protein product
70723
5.53
9%

1187
proapolipoprotein
28944
5.45
18%

1187
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
3%

1187
histidine-rich glycoprotein precursor
60510
7.09
8%

1187
vitamin D-binding protein precursor
54526
5.40
8%

1187
dermcidin preproprotein
11391
6.08
10%

1187
complement C4B precursor
189599
7.39
3%

1187
inter-alpha-trypsin inhibitor family heavy chain-related
103536
6.64
2%

protein

1187
Plasminogen
93263
6.89
1%

1187
alpha-2-antiplasmin precursor
54536
5.71
2%

1187
Chain A, Crystal Structure Of Native Heparin Cofactor Ii
55096
6.26
3%

1187
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1187
complement 9
661728
5.42
7%

1187
Alpha-2-macroglobulin precursor (Alpha-2-M)
164600
6.00
1%

1187
Vitamin K-dependent protein S precursor
77127
5.48
2%

1187
lumican
38717
6.16
4%

1187
hyaluronan binding protein 2
64740
6.09
1%

1187
Chain A, Crystallographic Analysis Of The Human Vitamin
52780
5.17
54%

D Binding Protein

1187
antithrombin III
53041
6.32
23%

1187
alpha-2-antiplasmin precursor
54536
5.71
16%

1187
putative
2269
9.79
38%

1187
complement component C4A
194337
6.65
1%

1187
alpha 2-plasmin inhibitor, alpha 2-PI {N-terminal, form A}
2064
5.43
63%

[human, plasma, Peptide Partial, 19 aa]

1187
lumican
38717
6.16
15%

1187
dermcidin preproprotein
11391
6.08
10%

1187
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
2%

(putative function)

1187
kininogen 1
48936
6.29
2%

1187
Plasminogen
93263
6.89
1%

1187
alpha2-HS glycoprotein
36268
5.20
2%

1187
fetuin-like protein IRL685
42922
6.87
3%

1187
Creatine kinase, muscle
43268
6.77
7%

1187
PREDICTED: similar to Cyclin G-associated kinase
148776
9.19
0%

1187
KIAA1277 protein
118159
9.14
1%

1206
trypsin inhibitor
106647
6.58
6%

1206
Chain A, Annexin A2: Does It Induce Membrane
38638
6.92
9%

Aggregation By A New Multimeric State Of The Protein

1206
prepro-C3b/C4B inactivator
65725
7.72
10%

1206
trypsin (EC 3.4.21.4) III precursor - human
26759
5.95
15%

1206
hemopexin precursor
51512
6.57
13%

1206
phospholipase D3 isoform 2
48740
6.00
2%

1206
plasma serine protease inhibitor precursor
45772
9.38
2%

1206
WD repeat domain, phosphoinositide interacting 2 isoform b
47513
5.68
2%

1214
prepro-C3b/C4B inactivator
63725
7.72
26%

1214
complement component C3
187046
6.02
6%

1214
pigment epithelial-differentiating factor
46300
5.84
13%

1214
immunoglobulin heavy chain variable region
9196
6.92
13%

1214
lymphoid-restricted membrane protein
56178
5.44
1%

1214
neuron growth inhibitory factor
6932
4.79
22%

1215
unnamed protein product
65696
7.38
27%

1215
glucosamine
62840
8.60
6%

1215
fibrinogen beta chain
52759
8.33
12%

1215
hemopexin precursor
52254
6.57
4%

1215
alpha-2-antiplasmin precursor
54536
5.71
2%

1215
phospholipase D3
49196
6.00
2%

1215
complement component C3
188585
6.02
0%

1215
cardiotrophin-like cytokine factor 1
25388
8.68
3%

1238
hemopexin precursor
51512
6.57
32%

1238
beta-fibrinogen precursor
54861
8.31
32%

1238
prepro-C3b/C4B inactivator
65725
7.72
6%

1238
dermcidin preproprotein
11277
6.08
20%

1238
Fc fragment of IgG binding protein
571718
5.14
1%

1238
phospholipase D3 isoform 2
48740
6.00
2%

1238
annexin A2 isoform 2
38580
7.57
6%

1238
unnamed protein product
15956
7.12
8%

1238
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
101326
6.31
4%

heavy chain H1) (Inter-alpha-inhibitor heavy chain 1)

(Inter-alpha-trypsin inhibitor complex component III)

(Serum-derived hyaluronan-associated protein) (SHAP)

1238
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
38273
8.34
2%

(Apolipoprotein H) (Apo-H) (B2GPI) (Beta(2)GPI)

(Activated protein C-binding protein) (APC inhibitor)

(Anticardiolipin cofactor)

1238
regucalcin
33231
5.89
5%

1238
granulocyte colony-stimulating factor receptor
85066
8.33
0%

1238
cAMP-specific phosphodiesterase PDE4D5
84375
5.03
1%

1242
fibrinogen beta chain, isoform CRA_d
52759
8.33
25%

1242
putative
2269
9.79
38%

1242
annexin A2 isoform 2
38808
7.57
6%

1242
hemopexin precursor
52254
6.57
4%

1242
phospholipase D3 isoform 2
49196
6.00
2%

1242
antithrombin III
53041
6.32
3%

1242
beta globin chain
11537
5.90
21%

1242
granulocyte colony-stimulating factor receptor
86548
8.33
0%

1242
KIAA1904 protein
90787
7.63
1%

1242
complement component C3
188585
6.02
0%

1242
unnamed protein product
71246
5.92
1%

1242
aberrant LSLCL
33536
6.82
6%

1263
hemopexin precursor
52254
6.57
17%

1263
prepro-C3b/C4B inactivator
68120
7.72
9%

1263
beta-fibrinogen precursor
55545
8.31
10%

1263
phospholipase D3 isoform 2
49196
6.00
2%

1263
annexin A2
38808
7.57
6%

1263
unnamed protein product
16070
7.12
14%

1263
regucalcin
33802
5.89
5%

1263
trypsin
27329
5.95
5%

1263
lysosomal acid phosphatase 2 precursor
48713
6.28
4%

1263
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1263
granulocyte colony-stimulating factor receptor
86548
8.33
0%

1263
chain A, Hr1b Domain Form Prk1
9054
9.77
11%

1290
hemopexin precursor
52254
6.57
14%

1290
annexin A2 isoform 2
38808
7.57
6%

1290
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
3%

1290
regucalcin
33802
5.89
5%

1290
unnamed protein product
16070
7.12
8%

1290
phospholipase D3 isoform 2
49196
6.00
2%

1290
Plasminogen
93263
6.89
1%

1290
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1290
granulocyte colony-stimulating factor receptor
86548
8.33
5%

1290
hCG2007940
12771
10.89
6%

1290
Rho guanine nucleotide exchange factor (GEF) 17
223645
5.90
0%

1323
annexin A2 isoform 2
38580
7.57
12%

1323
glucosamine (N-acetyl)-6-sulfatase precursor
62042
8.60
7%

1323
hemopexin, isoform CRA_d
43201
6.24
9%

1323
plasma serine protease inhibitor precursor
45772
9.38
5%

1323
Trypsin-3 precursor (Trypsin III) (Brain trypsinogen)
32478
7.46
10%

(Mesotrypsinogen)

1323
cartilage linking protein 1
40140
7.10
2%

1323
dermcidin preproprotein
11277
6.08
10%

1323
phospholipase D3 isoform 2
48740
6.00
2%

1323
glutathione S-transferase GSTM5-5
25676
6.90
11%

1326
procollagen C-endopeptidase enhancer 1 precursor
48797
7.41
47%

1326
homopexin precursor
52254
6.57
36%

1326
cartilage linking protein 1
40767
7.10
22%

1326
dynein light chain 2
10457
6.81
26%

1326
trypsin (EC 3.4.21.4) III precursor - human
27329
5.95
9%

1326
Chain A, Structure Of Human Annexin A2 In The Presence
36631
8.32
21%

Of Calcium Ions

1326
Chain A, Structure Of Human Trypsin Iv (Brain Trypsin)
24832
6.56
10%

1326
lysosomal acid phosphatase 2 precursor
48713
6.28
8%

1326
alpha-2-macroglobulin precursor
164600
6.00
5%

1326
PREDICTED: similar to Hornerin
188565
9.82
5%

1326
type II intermediate filament of hair keratin
54756
5.48
11%

1326
filaggrin 2
249296
8.45
0%

1326
Beta-2-glycoprotein 1 precursor (Beta-2-glycoprotein I)
39584
8.34
2%

(Apolipoprotein H)

1326
complement component C3
188585
6.02
3%

1326
glutathione transferase M3
27127
5.37
4%

1326
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
2%

1326
phospholipase D3 isoform 1
55127
6.02
6%

1326
regucalcin
33802
5.89
5%

1326
Chain B, Non-Covalent Complex Between Alpha-1-Pi-
26077
8.23
4%

Pittsburgh And S195a Trypsin

1326
general transcription factor IIIC, polypeptide 4, 90 kDa
93140
6.27
1%

1326
dermcidin preproprotein
11391
6.08
10%

1327
hemopexin precursor
52254
6.75
41%

1327
enolase 1
47481
7.10
35%

1327
coronin-like protein
51722
6.12
11%

1327
alpha-2-macroglobulin precursor
164600
6.00
7%

1327
annexin A2 isoform 2
38808
7.57
12%

1327
complement component C3
188585
6.02
3%

1327
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.60
2%

1327
trypsin III precursor
27329
5.95
9%

1327
arylsulfatase B precursor
60195
8.30
3%

1327
phospholipase D3 isoform 2
49196
6.00
4%

1327
lysosomal acid phosphatase 2 precursor
48713
6.28
5%

1327
PREDICTED: similar to ribosomal protein L36
5528
10.50
21%

1327
antigen MLAA-44
42961
5.11
1%

1327
granulocyte colony-stimulating factor receptor
86548
8.33
0%

1327
angiotensin I converting enzyme 1
134639
5.98
1%

1361
complement component C3
188585
6.02
11%

1361
annexin A2 isoform 2
38808
7.57
16%

1361
lysosomal acid phosphatase 2 precursor
48713
6.28
8%

1361
protease serine 1
9218
10.28
30%

1361
carboxypeptidase N, polypetide 1, 50 kD precursor
52538
6.86
6%

1361
cartilage linking protein 1
40767
7.10
11%

1361
phospholipase D3 isoform 2
49196
6.00
2%

1361
dermcidin preproprotein
11391
6.08
10%

1361
neuropolypeptide h3
16068
8.81
14%

1361
arylsulfatase B precursor
60195
8.43
8%

1361
Plasminogen
93263
6.89
1%

1361
chain, annexin I
35246
7.77
5%

1361
hemopexin precursor
52254
6.57
6%

1361
mutant beta-globin
12635
5.09
20%

1361
alpha-fibrinogen precursor
70223
8.26
5%

1361
unnamed protein product
79911
8.51
1%

1548
afamin precursor
69024
5.64
10%

1548
trypsin inhibitor
106647
6.58
1%

1548
Inter-alpha-trypsin inhibitor heavy chain H1 precursor (ITI
101326
6.31
5%

heavy chain H1) (Inter-alpha-inhibitor heavy chain 1)

(Inter-alpha-trypsin inhibitor complex component III)

(Serum-derived hyaluronan-associated protein) (SHAP)

1548
Alpha-2-macroglobulin precursor (Alpha-2-M)
163175
6.00
1%

1548
beta-fibrinogen precursor
54861
8.31
11%

1548
anti-colorectal carcinoma heavy chain
50570
6.22
2%

1646
unnamed protein product
70723
5.53
15%

1646
annexin A2 isoform 2
38808
7.57
15%

1646
transaldolase 1
37688
6.36
14%

1646
putative
2269
9.97
38%

1646
dermcidin preproprotein
11391
6.08
10%

1646
tousled-like kinase 1
82461
8.82
2%

1778
apolipoprotein J precursor
49342
6.27
22%

1778
chain A, annexin V
35840
4.94
8%

1778
annexin A2 isoform 2
38808
7.57
10%

1778
inter-alpha-trypsin inhibitor
103549
6.51
3%

1778
trypsin-3 precursor
33276
7.46
10%

1778
complement factor B
86819
6.55
1%

1778
apolipoprotein E
36302
5.65
6%

1778
regucalcin
33802
5.89
5%

1778
filaggrin 2
249296
8.45
1%

1778
chain, x-ray crystal structure of C3d
32959
6.34
9%

1778
plasminogen
93263
6.89
1%

1778
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

2045
complement component C3
188585
6.02
7%

2045
poly-Ig
76443
5.38
4%

2045
putative
2269
9.79
38%

2045
PREDICTED: similar to CG6405-PA
37748
6.37
2%

2045
Chain A, Crystal Structure Of Human Tr Alpha Bound T3
30656
5.41
14%

In Orthorhombic Space Group

2045
LARP
42148
5.48
4%

2045
hypothetical protein LOC400867
15522
10.07
4%

2158
putative
2269
9.79
38%

2284
chain A . . . apolipoprotein
28061
5.27
62%

2284
putative
2269
9.79
38%

2284
tenascin
246210
4.80
0%

2284
Chain A, Structure Of Human Trypsin Iv (Brain Trypsin)
24832
6.56
5%

2284
glutathione transferase M3
27127
5.37
6%

2284
chain A, aspartylglucosaminidase
17552
4.82
9%

2284
unnamed protein product
23195
5.48
5%

2284
dermcidin preproprotein
11391
6.08
10%

2284
ATP binding domain 3
37296
9.58
2%

2284
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
5%

2285
Chain A, Crystal Structure of Lipid-Free human
28061
5.27
82%

apolipoproprotein A-I

2285
unnamed protein
23195
5.48
24%

2285
putative
2269
9.79
38%

2285
DEP domain containing 1, isoform CRA
84786
8.71
0%

2285
glutathione transferase M3
27127
5.37
7%

2285
PREDICTED: hypothetical protein
47324
12.09
1%

2285
unnamed protein product
71246
5.92
1%

2285
Chain A, Trypsin (E.C.3.4.21.4) Complexed With The
24669
7.64
3%

Inhibitor Diisopropyl-Fluorophosphofluoridate (Dfp)

2305
Chain A, Crystal Structure of Lipid-Free Human
28061
5.27
44%

Apolipoprotein A-1

2305
putative
2269
9.79
38%

2305
dermcidin preproprotein
11391
6.08
10%

2305
plasminogen
93263
6.89
1%

2305
hCG22067
30319
7.98
3%

2305
unnamed protein product
71246
5.92
1%

2305
supported by mouse EST AA538043 (NID: g2284036)
37423
9.28
2%

2305
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
2%

2305
Chain A, Human Aspartylglucosaminidase
17552
4.82
4%

2364
C-type lectin domain family 3, member b, isoform CRA_a
22921
5.52
37%

2364
hypothetical protein LOC79017
21222
5.07
8%

2364
putative
2269
9.79
38%

2364
lipoprotein Gln I
28329
5.27
26%

2364
unnamed protein product
112600
8.27
0%

2364
PRSS3 protein
27040
6.86
8%

2364
Chain A, Solution Structure Of The Human Defensin Hbd-2
4345
9.50
16%

2364
KIAA1481 protein
150746
6.77
0%

2609
putative
2269
9.79
38%

2609
Chain B, Crystal Structure Of A Rac-Rhogdi Complex
20521
6.16
12%

2609
dismutase, Cu/Zn superoxide
16020
8.76
16%

2609
hypothetical protein LOC51250
28038
9.31
2%

2609
proteasome 26S non-ATPase subunit 10 isoform 1
24697
5.71
6%

2609
hCG2044987
11472
9.73
8%

44
fibronectin precursor
266034
5.45
27%

44
complement component C3
188585
6.02
17%

44
alpha-2-macroglobulin precursor
164600
6
10%

44
hemopexin precursor
52254
6.57
27%

44
semenogelin II precursor
65519
9.08
3%

44
cAMP-specific phosphodiesterase
84945
5.03
2%

82
fibronectin precursor
266034
5.45
7%

82
plasma protease (C1) inhibitor precursor
55375
6.09
16%

82
Chain B, Structure of Complement C3b
104912
5.18
8%

82
megakaryocyte stimulating factor
152195
9.53
4%

82
alpha-1-antitrypsin
46848
5.43
14%

109
fibronectin 1 isoform 3 preproprotein
262656
5.49
23%

109
factor H
143710
6.28
7%

109
alpha-1-antitrypsin
13859
5.43
21%

109
alpha-2-macroglobulin precursor
164600
6
1%

109
complement component C3
188585
6.02
2%

126
fibronectin 1 isoform 3 preproprotein
262656
5.49
22%

126
alpha-2-macroglobulin precursor
164600
6
10%

126
complement component C3
188585
6.02
3%

126
unnamed protein, serum protein
71246
5.92
6%

126
gelsolin
86043
5.9
4%

126
hemopexin precursor
52254
6.57
2%

164
fibronectin 1 isoform 3 preproprotein
262656
5.49
23%

164
macroglobulin alpha 2
162072
5.95
19%

164
gelsolin
52511
5.21
6%

175
fibronectin precursor
260064
5.45
6%

175
inter-alpha-trypsin family heavy chain-related protein
103549
6.51
6%

175
thyroxine-binding globulin precursor
46637
5.87
11%

175
afamin precursor
70963
5.64
1%

175
complement component C3
188585
6.02
4%

175
attractin-2
146159
6.65
1%

175
annexin A2 isoform 2
38808
7.57
7%

175
alpha-1-antitrypsin
13859
7.93
21%

184
alpha 2 macroglobulin
167505
6.06
21%

184
mutant beta-globin
16098
7.14
19%

191
alpha-1-antitrypsin precursor
46849
5.51
22%

191
alpha-2-macroglobulin precursor
164,000
6
8%

191
complement component C3
188585
6.02
5%

191
hemopexin precursor
52254
6.57
9%

191
fibronectin precursor
260064
5.45
3%

205
alpha-1-antichymotrypsin
48834
5.79
3%

205
aggrecan core protein precursor
251979
4.1
0%

205
creatine kinase M
43247
6.63
3%

213
alpha-1-antitrypsin
22871
6.11
36%

216
collagen type IV alpha 1
161654
8.55
3%

216
annexin A2 isoform 2
38808
7.57
16%

216
alpha 2 type IV collagen preproprotein
168646
8.89
5%

244
collagen type IV alpha 1
161654
8.55
3%

244
annexin A2 isoform 2
38808
7.57
16%

244
alpha 2 type IV collagen preproprotein
168646
8.89
5%

252
alpha 2 macroglobulin
167505
6.06
23%

252
complement factor H
143694
6.21
24%

252
complement component C3
188585
6.02
9%

252
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

252
hemopexin precursor
52254
6.57
8%

252
annexin A2 isoform 2
38808
7.57
5%

267
Human Factor H (Four models determined by solution
141553
6.19
10%

Scattering)

267
inter-alpha-trypsin inhibitor
103549
6.51
8%

267
fibronectin precursor
260064
5.45
2%

267
afamin precursor
70963
5.64
5%

267
complement C4B precursor
189599
7.39
8%

267
serpin peptidase inhibitor, clade B
44313
5.32
15%

267
alpha-2-macroglobulin
164600
6
1%

267
inter-alpha-trypsin inhibitor, C-terminal
93745
6.02
1%

267
C9 complement protein
64399
5.49
1%

267
ceruloplasmin
98321
5.29
2%

267
serpin B8
43328
5.43
10%

295
complement factor H
143694
6.21
34%

295
alpha 2 macroblobulin
167505
6.06
15%

295
trypsin inhibitor
107103
6.58
10%

295
inter-alpha-trypsin inhibitor
101782
6.31
5%

295
complement component C3
188585
6.02
2%

305
complement factor H
143694
6.21
39%

305
alpha 2 macroglobulin
167505
6.06
9%

305
inter-alpha-trypsin inhibitor
106826
6.4
10%

305
inter-alpha trypsin inhibitor heavy chain H1 precursor
101782
6.31
8%

305
hemopexin precursor
52254
6.57
4%

352
complement factor H
143694
6.21
35%

352
alpha-2-macroglobulin precursor
164600
6
12%

352
inter-alpha-trypsin inhibitor heavy chain H1 precursor
101782
6.31
10%

352
trypsin inhibitor
107103
6.58
9%

352
complement component C3
188585
6.02
6%

352
Protein S100-A7
11564
6.27
21%

392
ceruloplasmin
116197
5.43
15%

392
inter-alpha-trypsin family heavy chain-related protein
103549
6.51
15%

392
phosphatidylinositol-glycan-specific phospholipase D1
92943
5.91
7%

precursor

392
alpha-2-macroglobulin precursor
164600
6
3%

392
complement C4B
189599
7.39
1%

392
creatine kinase M
43247
6.63
3%

396
ceruloplasmin
116197
5.43
19%

396
inter-alpha-trypsin inhibitor family heavy chain-related
103549
5.43
19%

protein

396
inter-alpha-trypsin family heavy chain-related protein
103549
6.51
15%

396
afamin precursor
70963
5.64
15%

396
C9 complement protein
64399
5.49
7%

396
complement C4B
189599
7.39
1%

396
plasminogen
93263
6.89
1%

469
Chain B, Human Complement Component C3
112869
5.55
27%

469
ceruloplasmin
115398
5.43
5%

469
complement component 6, isoform CRA_b
105683
6.41
6%

469
hypothetical protein (macroglobulin alpha2 ?)
163207
6
28%

509
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
23%

protein

509
ceruloplasmin
115398
5.43
17%

509
Chain B, Structure of Complement C3b
103886
5.18
8%

509
regucalcin
33231
5.89
5%

509
serpin peptidase inhibitor, clade F
57016
6.47
9%

509
coagulation factor II precursor variant
70091
5.7
6%

509
Chain A, G68a Human Lysozyme
14705
9.28
41%

509
afamin precursor
69024
5.64
8%

510
ceruloplasmin (ferroxidase)
116685
5.48
12%

510
Chain A, Crystal Structure of human Galectin-7 In complex
14935
7
27%

with Galactosamine

510
unnamed protein (S100 calcium-binding protein)
10931
9.19
46%

510
inter-alpha-trypsin inhibitor family heavy chain-related
103308
6.64
8%

protein

510
calmodulin-like skin protein
15911
4.34
19%

510
SCCA2/SCCA1 fusion protein isoform 1
44620
5.99
12%

510
Protein S100-A7 (Psoriasin)
11450
6.27
33%

510
small proline-rich protein
8049
9.07
25%

510
fatty acid binding protein 5
15155
6.6
40%

510
tubulin, beta, 4
88325
5.55
6%

512
ceruloplasmin (ferroxidase)
116685
5.48
7%

512
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
9%

protein

547
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
20%

protein

547
complement component C3
187046
6.02
13%

547
alpha-2-macroglobulin
70751
5.47
16%

547
ceruloplasmin (ferroxidase)
116685
5.48
9%

547
complement component C3b
25280
4.49
16%

547
fibrinogen gamma
46252
5.54
9%

547
Chain A, Factor H
136992
6.19
12%

547
serum albumin
69349
6.13
7%

553
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
22%

protein

553
ceruloplasmin
115398
5.43
15%

553
complement component C3
187046
6.02
13%

553
COMP
82780
4.34
5%

553
Chain E, Prethrombin2
33789
8.32
19%

553
lumican
38375
6.16
11%

553
alpha-2-macroglobulin precursor
163175
6
5%

553
prepro-C3b/C4B
65725
7.72
5%

553
afamin precursor
69024
5.64
13%

553
beta-globin
18919
6.28
12%

554
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
16%

protein

554
complement component C3
187046
6.02
16%

554
alpha-2-macroglobulin precursor
163175
6
9%

554
ceruloplasmin
115398
5.43
7%

554
annexin A2, isoform CRA_c
32429
5.93
16%

554
alpha-2-antiplasmin precursor
54194
5.71
3%

554
hemopexin precursor
51512
6.57
7%

554
inter-alpha (globulin) inhibitor H1
101339
6.31
9%

555
complement component C3
187046
6.02
29%

555
alpha-2-macroglobulin precursor
163175
6
11%

555
inter-alpha-trypsin inhibitor
106370
6.4
5%

555
ceruloplasmin
115398
5.43
6%

555
ALB protein
71658
6.42
13%

555
hemopexin precursor
51512
6.57
12%

555
fibrinogen gamma chain
47344
5.54
14%

555
annexin A2, isoform 2
38580
7.57
8%

555
alpha-2-anti-plasmin precursor
54194
5.71
4%

555
gelsolin isoform a precursor
85644
5.9
3%

561
complement component C3
187046
6.02
32%

561
alpha-2-macroglobulin precursor
163175
6
12%

561
trypsin inhibitor
106647
6.58
5%

561
annexin A2, isoform 2
38580
7.57
15%

561
plasminogen
57372
7.42
9%

561
serum albumin
69349
6.13
9%

561
hemopexin
51512
6.57
11%

561
fibrinogen gamma
46252
5.54
7%

561
complement factor H
139019
6.21
5%

567
Chain B, Human complement component C3
112869
5.55
53%

567
alpha 2 macroglobulin
166022
6.06
10%

567
hemoglobin beta
15866
5.23
14%

567
hemopexin precursor
51512
6.57
13%

568
complement component C3
187046
6.02
29%

568
complement factor B
85450
6.55
9%

568
macroglobulin alpha
160704
5.95
13%

568
gelsolin isoforma precursor
85644
5.9
8%

568
S100 calciium-binding protein A9
13234
5.71
19%

655
complement component 4A preprotein
192665
7.39
10%

655
afamin precursor
69024
5.64
27%

655
ceruloplasmin (ferroxidase)
116685
5.48
19%

655
alpha-2-macroglobulin precursor
163175
6
14%

655
Chain B, Structure of Complement C3b
103886
5.18
20%

655
hypothetical protein inter-alpha (globulin inhibitor H4
70808
5.86
16%

655
fibulin-1 isoform D precursor
77223
5.11
9%

655
alpha-1-B-glycoprotein
51908
5.65
6%

655
valosin-containing protein
89266
5.14
17%

655
inter-alpha-trypsin inhibitor C-terminal
93402
6.02
3%

655
Vitamin D-binding protein precursor
52929
5.4
16%

655
complement C5 precursor
188212
6.11
3%

655
C9 complement protein
62974
5.49
11%

655
trypsin inhibitor
106647
6.58
9%

655
fibrinogen
46252
5.54
8%

655
serpin B6 (placental thrombin inhibitor)
42562
5.18
9%

677
alpha 2 macroglobulin variant
164030
6
16%

677
complement component C3
187046
6.02
20%

677
complement factor B
85450
6.55
16%

677
unnamed protein (complement component 2 precursor)
83180
7.23
7%

677
annexin A2
38552
7.57
18%

677
complement protein C7 precursor
93453
6.09
7%

677
hemopexin precursor
51512
6.57
16%

701
alpha 2 macroglobulin variant
164030
6
20%

701
complement component C3
1870046
6.02
11%

701
annexin A2 isoform 2
38580
7.57
10%

701
ANXA1 protein
5273
4.66
27%

703
alpha 2 macroglobulin variant
164030
6
16%

703
complement component 3 precursor
187030
6.02
12%

703
inter-alpha-trypsin inhibitor family heavy chain-related
103321
6.51
4%

protein

703
ceruloplasmin (ferroxidase)
116685
5.48
5%

704
alpha 2 macroglobulin precursor
164600
6
9%

704
hornerin precursor
188565
9.82
4%

704
beta-globin
19204
6.28
12%

704
complement component C3
188585
6.02
1%

704
cAMP-specific phosphodiesterase
84945
5.03
1%

704
SCP-1
114424
5.84
3%

712
complement component 1, s subcomponent
78174
4.86
21%

712
inter-alpha-trypsin inhibitor
99401
5.61
9%

712
lumican
38717
6.16
24%

712
ASPIC
71448
4.98
12%

712
afamin precursor
70963
5.64
14%

712
Vitamin K-dependent protein
77127
5.48
9%

712
trypsin inhibitor
107103
6.58
5%

712
lysosomal membrane glycoprotein-2
45374
5.47
1%

712
gelsolin
86043
5.9
2%

712
Chain L, alpha-thrombin
4145
4.65
27%

712
crystal structure of protein phosphatase 2a
65173
5.07
6%

712
cAMP-specific phospodiesterase
84945
5.03
1%

729
plasma kallikrein precursor (kininogenin)
73433
8.6
16%

729
S100 calcium-binding protein A9
13291
5.71
43%

729
Chain A, crystal structure of human galectin-7 in complex
14992
7
40%

with galactosamine

729
glyceraldehyde-3-phosphate dehydrogenase
36202
8.26
14%

729
Protein S100-A7 (psoriasin)
11564
6.27
23%

729
stratifin
27871
4.68
22%

744
gelsolin isoform a precursor
86043
5.9
22%

744
alpha-2-macroglobulin precursor
164600
6
3%

744
fibrinogen gamma chain
50077
5.61
7%

744
Chain B, Alpha-Ferrous-Carbonmonoxy
16070
7.12
17%

744
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
1%

744
hemopexin precursor
52254
6.57
6%

744
Complement C1r subcomponent precursor
81661
5.89
2%

744
unnamed protein product (UDP glucuronosyltransferase)
51813
7.62
2%

745
gelsolin isoform a precursor
86043
5.9
14%

745
annexin A2 isoform 2
38808
7.57
9%

745
alpha 2 macroglobulin
167505
6.06
2%

745
coagulation factor XIII B chain
77723
5.97
1%

745
KIAA1134 protein
68436
5.69
6%

748
gelsolin isoform a precursor
86043
5.9
26%

748
coagulation factor XIII
77723
5.97
18%

748
fibrinogen gamma chain
50077
5.61
18%

748
Chain B, Alpha-Ferrous-Carbonmonoxy,
15971
6.81
23%

748
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
6%

748
annexin A2 isoform
38808
7.57
8%

748
macroglobulin alpha2
162072
5.95
5%

748
hemopexin precursor
52254
6.57
8%

748
Complement C1r subcomponent precursor
81661
5.89
1%

748
inter-alpha (globulin) inhibitor H1
101816
6.43
4%

763
afamin precursor
70963
5.64
31%

763
inter-alpha-trypsin inhibitor
106826
6.4
14%

763
coagulation factor II precursor
71475
5.64
27%

763
insulin-like growth factor binding protein, acid labile
66735
6.33
18%

763
inter-alpha (globulin) inhibitor H4
103521
6.51
16%

763
Chain A, crystal Structure of Lipid-Free Human
28061
5.27
35%

Apolipoprotein A-I

763
alpha-1-B-glycoprotein
52479
5.65
17%

763
histidine-rich glycoprotein precursor
60510
7.09
12%

763
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
5%

763
phospholipid transfer protein isoform a precursor
54933
6.53
10%

763
C9 complement protein
64399
5.49
11%

763
complement C4B precursor
189599
7.39
4%

763
hemopexin precursor
52254
6.57
11%

763
coagulation factor XII
68618
7.94
5%

763
antithrombin III
53041
6.32
10%

763
ceruloplasmin
98321
5.29
3%

763
Chain B, Structure of Complement C3b: Insights Into

5.18
3%

Complement Activation and Regulation

763
lumican
38717
6.16
9%

763
serpin peptidase inhibitor clade I
46287
5.08
5%

763
Chain B, Crystal structure of S-Nitroso-Nitrosyl Human
15922
6.81
28%

Hemoglobin A

763
plasma kallikrein precursor
73433
8.6
1%

763
complement component 5 variant
124357
8.43
1%

764
gelsolin isoform a precursor
86043
5.9
35%

764
coagulation factor XIII B chain
77723
5.97
23%

764
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
7%

764
complement C1r subcomponent precursor
81661
81661
6%

764
fibrinogen gamma
46823
5.54
7%

764
cAMP-specific phosphodiesterase
84945
5.03
1%

765
ASPIC
71448
4.98
29%

765
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
13%

protein

765
coagulation factor II precursor (unnamed protein product)
70723
5.53
20%

765
lumican
38717
6.16
28%

765
vitronectin (unnamed protein product)
55106
5.55
18%

765
complement component C4A
194337
6.65
3%

765
histidine-rich glycoprotein precursor
60510
7.09
10%

765
Biotinidase precursor
59730
5.5
6%

765
coagulation factor XII
68618
7.94
8%

765
inter-alpha-trypsin inhibitor heavy chain H3
99401
5.61
4%

765
plasma kallikrein
73433
8.6
5%

765
alpha-2-antiplasmin precursor
54536
5.71
6%

765
complement component C3
188585
6.02
1%

765
phospholipid transfer protein isoform a precursor
54933
6.53
2%

765
lysosomal membrane glycoprotein-2
45374
5.47
1%

765
trypsin inhibitor
107103
6.58
5%

765
inter-alpha-trypsin inhibitor
93745
6.02
1%

765
annexin A2 isoform 2
38808
7.57
2%

765
preproacrosin
46455
9.2
11%

765
beta globin chain variant
16117
6.75
25%

765
kininogen I
48936
6.29
8%

765
creatine kinase M
43427
6.63
3%

765
serum albumin (unnamed protein)
71246
5.92
1%

765
hemopexin precursor
52254
6.57
2%

765
NLR family member X1 isoform 1
108574
7
2%

766
afamin precursor
70963
5.64
34%

766
inter-alpha-trypsin inhibitor heavy chain H2 precursor
106826
6.4
16%

766
Chain B, Structure of Complement C3b
104912
5.18
14%

766
coagulation factor II precursor (unnamed protein)
70723
5.53
16%

766
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
11%

protein

766
Chain A, Crystal Structure of Lipid-Free Human
28061
5.27
44%

Apolipoprotein A-1

766
insulin-like growth factor binding protein, acid labile
66735
6.33
17%

subunit

766
alpha-1-B-glycoprotein
52479
5.65
17%

766
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
5%

766
serine (or cysteine) proteinase inhibitor, clade B
43004
5.61
6%

766
thrombin inhibitor
42901
5.33
3%

766
Complement C5 precursor
189923
6.11
3%

766
histidine-rich glycoprotein precursor
60510
7.09
10%

766
coagulation factor XII
68618
7.94
2%

766
C9 complement protein
64399
5.49
1%

766
lumican
38717
6.16
7%

766
hemopexin precursor
52254
6.57
7%

766
phospholipid transfer protein isoform a precursor
54933
6.53
2%

766
Chain A, Antithrombin Iii
49350
5.95
6%

766
Vitamin D-binding protein precursor
54526
5.4
2%

766
hornerin
48797
9.71
6%

770
gelsolin isoform a precursor
86043
5.9
28%

770
mitosin
360199
5.06
0%

770
macrophin 1 isoform 4
603087
5.05
0%

770
coagulation factor XIII B chain precursor
77723
5.97
5%

770
ret preprotein
32219
6.06
3%

776
trypsin inhibitor
107103
6.58
12%

776
insulin-like growth factor binding protein
66735
6.33
19%

776
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
5%

protein

776
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
5%

776
ceruloplasmin
98321
5.29
2%

776
Chain L, Alpha-Thrombin
4145
4.65
27%

776
histidine-rich glycoprotein
60510
7.09
7%

776
hemopexin precursor
52254
6.57
4%

776
coagulation factor XII
68618
7.94
1%

776
serine (or cysteine) proteinase inhibitor
42892
5.9
6%

776
proapolipoprotein
28944
5.45
8%

776
cAMP-specific phosphodiesterse
849945
5.03
1%

776
lumican
38717
6.16
5%

alpha-1-B-glycoprotein
52479
5.65
3%

818
vanin 1 precursor
57728
5.32
13%

818
coagulation factor II precursor (unnamed protein)
70723
5.53
11%

818
lumican
38717
6.16
25%

818
Biotinidase precursor
59730
5.5
4%

818
alpha-1-antichymotrypsin
48834
5.79
14%

818
vitronectin (unnamed protein)
55106
5.55
15%

818
aggrecan core protein precursor (Cartilage-specific
251979
4.1
1%

proteoglycan core protein)

818
coagulation factor XII
68618
7.94
8%

818
inter-alpha-trypsin inhibitor C-terminal
93745
6.02
2%

818
histidine-rich glycoprotein precursor
60510
7.09
5%

818
ASPIC
71448
4.98
5%

818
plasma protease (C1) inhibitor precursor
55375
6.09
9%

818
lysosomal membrane glycoprotein-2
45374
5.47
1%

818
Chain B, Structure of Complement C3b
104912
5.18
4%

818
extracellular protein
45048
5.26
3%

818
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
4%

protein

818
trypsin inhibitor
107103
6.58
6%

818
tumor endothelial marker 7-related precursor
60116
5.99
4%

COMP precursor
85403
4.34
3%

825
Chain B, Human Complement Component C3
114238
5.55
34%

825
inter-alpha-trypsin inhibitor heavy chain H!
101782
6.31
12%

825
extracellular matrix protein 1 isoform precursor
62262
6.25
16%

825
alpha-2-macroglobulin precursor protein
164600
6
4%

825
annexin A2 isoform 2
38808
7.57
8%

825
hemopexin precursor
52254
6.57
14%

825
complement C4B precursor
189599
7.39
6%

825
histidine-rich glycoprotein precursor
60510
7.09
5%

825
gelsolin isoform a precursor
86043
5.9
2%

825
alpha-2-antiplasmin precursor
54536
5.71
2%

825
Dopamine beta-hydroxylase precursor
68425
5.9
3%

825
peptidoglycan recognition protein L precursor
68699
7.62
3%

825
Chain A, Crystal Structure of Native Heparin Cofactor Ii
55096
6.26
7%

825
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
4%

825
beta-globin
15984
7.88
8%

827
lumican
38717
6.16
5%

827
inter-alpha-trypsin inhibitor heavy chain H1 precursor
101782
6.31
10%

827
Chain B, Structure of Complement C3b
104912
5.18
23%

827
Chain A, Crystal Structure of Native Heparin Cofactor Ii
55096
6.26
15%

827
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
9%

827
fibrinogen gamma chain
50077
5.61
13%

827
alpha-2-macroglobulin precursor
164600
6
6%

827
filaggrin 2
249296
8.45
2%

827
hornerin precursor
188565
9.82
5%

827
annexin A2 isoform 2
38808
7.57
5%

827
Chain B, T-To-T(High) Quaternary Transitions
15960
6.75
21%

827
hemopexin precursor
52254
6.57
8%

827
gp180-carboxypeptidase D-like enzyme
153903
5.7
3%

827
junction plakoglobin
82376
5.95
1%

827
coagulation factor Xii
68618
7.94
1%

833
desmoplakin I
334023
6.44
2%

833
inter-alpha (globulin) inhibitor H1, isoform CRA_b
99813
6.59
19%

833
complement component C3
188585
6.02
9%

833
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
15%

833
fibrinogen gamma chain
50077
5.61
23%

833
extracellular matrix protein 1 isoform 1 precursor
62262
6.25
5%

833
alpha-2-macroglobulin precursor
164600
6
6%

833
annexin A2 isoform 2
38808
7.57
8%

833
gp180-carboxypeptidase D-like enzyme
153903
5.7
65

833
hemopexin precursor
52254
6.57
6%

833
Chain A, Hr1b Domain from Prk1
9054
9.77
11%

833
glutathione transferase M3
27127
5.37
4%

844
matrix, extracellular phosphoglycoprotein with ASARM
58498
8.62
11%

motiff

844
alpha-1-B-glycoprotein
52479
5.65
22%

844
alpha-2-antiplasmin precursor
54536
5.71
14%

844
lumican
38717
6.16
28%

844
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
9%

protein

844
Chain B, Structure of Complement C3b
104912
5.18
12%

844
complement component 1
78174
4.86
15%

844
hemopexin precursor
52254
6.57
14%

844
Chain B, T-To-T (High) Quaternary Transitions In Human
15960
6.75
15%

hemoglobin

844
histidine-rich glycoprotein precursor
60510
7.09
10%

844
vitronectin precursor (unnamed protein)
55106
5.55
11%

844
coagulation factor II precursor (unnamed protein)
71475
5.64
7%

844
kininogen 1
48936
6.29
8%

844
preproacrosin
46455
9.2
11%

844
complement component 1
54192
6.75
4%

844
alpha-2-plasmin inhibitor
2064
4.53
63%

844
Vitamin K-dependent protein S precursor
77127
5.48
4%

846
ASPIC
71448
4.98
2%

846
alpha-1-B-glycoprotein
52479
5.65
24%

846
inter-alpha-trypsin inhibitor
103549
6.51
15%

846
Vitamin K-dependent protein S precursor
77127
5.48
22%

846
Chain B, Human Complement Component C3
114238
5.55
19%

846
coagulation factor II (unnamed protein)
70723
5.64
12%

846
histidine-rich glycoprotein precursor
60510
7.09
13%

846
Chain B, T-To-T (High) Quaternary Transitions In Human
15960
6.75
23%

Hemoglobin

846
alpha-2-antiplasmin precursor
54536
5.71
14%

846
hemopexin
52254
6.57
16%

846
lumican
38717
6.16
7%

846
complement component C4A
18042
5.08
8%

846
complement 9
61728
5.42
8%

846
kininogen 1
72954
6.34
4%

846
inter-alpha-trypsin inhibitor
93745
6.02
4%

846
phospholipid transfer protein isoform a precursor
54933
6.53
4%

846
GRP78
72185
5.03
4%

846
complement component 1
54192
6.75
4%

846
Chain A, Hemoglobin Thionville Alpha Chain Mutant with
15446
7.82
16%

Val 1 replaced . . .

846
creatine kinase M
43247
6.63
6%

846
Chain A, Crystal Structure of Native heparin Cofactor Ii
55096
6.26
5%

846
Chain A, Antithrombin Iii
49350
5.95
3%

920
afamin precursor
70963
5.64
6%

920
complement C4B precursor
189599
7.39
12%

920
complement component 3
144417
8.24
12%

920
inter-alpha-trypsin inhibitor heavy
101782
6.31
3%

920
hemoglobulin beta chain variant Hb S-Wake
16045
7.12
23%

920
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
2%

920
Chain, Annexin I
35246
7.77
10%

920
phospholipase D3 isoform 2
49196
6
2%

920
hornerin
48797
9.71
7%

920
annexin A2 isoform 2
38808
7.57
7%

920
butyrophilin
82036
8.4
1%

937
chaperon containing TCP1, subunit 7 isoform a
59842
7.55
4%

937
complement C4B precursor
189599
7.39
13%

937
complement component 3 precursor
188569
6.02
10%

937
annexin A2 isoform 2
38808
7.57
8%

937
armadillo repeat-containing protein
31489
5.54
5%

927
cAMP-specific phosphodiesterase
84945
5.03
3%

972
kininogen 1
48936
6.29
41%

972
vitronectin (unnamed protein)
55099
5.55
16%

972
lumican
38717
6.16
24%

972
angiotensinogen
53407
5.78
11%

972
alpha-2-antiplasmin precursor
54536
5.71
9%

972
extracellular protein
45048
5.26
17%

972
ectonucleotide pyrophosphatase
54745
5.94
7%

972
hemopexin precursor
52254
6.57
8%

972
C9 complement protein
64399
5.49
14%

972
carnosinase 1
56770
5.14
9%

972
complement component C3
188585
6.02
1%

981
creatine kinase M
43247
6.63
3%

981
complement component 3
144417
8.24
23%

981
complement C4B precursor
189599
7.39
5%

981
annexin A2 isoform 2
38808
7.57
9%

982
armadillo repeat-containing protein
31489
5.54
5%

982
complement component 3
144417
8.24
23%

982
complement C4B precursor
189599
7.39
4%

982
annexin A2 isoform 2
38808
7.57
3%

983
cAMP-specific phosphodiesterase
84945
5.03
1%

983
kininogen 1
48936
6.29
48%

983
lumican
38717
6.16
18%

983
alpha-2-antiplasmin precursor
54536
5.71
4%

983
apolipoprotein D
28317
5.14
17%

983
ectonucleotide pyrophosphatase
54745
5.94
3%

983
angiotensinogen
53407
5.78
8%

983
thyroxine-binding globulin precursor
46637
5.87
3%

983
extracellular protein
45048
5.26
3%

983
C9 complement protein
64399
5.49
3%

983
ASPIC
71448
4.98
1%

983
creatine kinase M
43247
6.63
3%

983
cAMP-specific phosphodiesterase
84945
5.03
1%

983
hemopexin precursor
52254
6.57
5%

983
LYST-interacting protein
26297
9.09
2%

983
ubiquitin
8446
6.56
12%

983
alpha-1-antichymotrypsin
48834
5.79
3%

990
complement C8-beta propeptide
63605
8.24
3%

990
complement component 3
144417
8.24
18%

1098
hornerin
48797
9.71
6%

1098
alpha 2 macroglobulin
167505
6.06
5%

1098
annexin A2 isoform 2
38808
7.57
19%

1098
plasma carboxypeptidase B2 isoform a preproprotein
48982
7.61
6%

1098
selenoprotein P
43727
7.87
13%

1098
antithrombin III
53041
6.32
12%

1098
kallistatin
48696
7.33
11%

1098
Beta-2-glycoprotein 1 precursor
39584
8.34
11%

1098
hemopexin precursor
52254
6.57
10%

1098
phospholipase D3 isoform
49196
6
2%

1098
glutathione transferase M3
27127
5.37
4%

1098
calcium binding protein 39 (unnamed protein)
33844
6.67
3%

1098
Chain A, Crystal Structure Analysis of the Bb Segment of
56816
7.16
8%

Factor B

1105
kininogen
4228
6.52
34%

1105
Chain A, antithrombin Iii
49350
5.95
47%

1105
angiotensinogen
53407
5.78
19%

1105
thyroxine-binding globulin precursor
46637
5.87
27%

1105
kininogen 1
48936
6.29
21%

1105
complement C4B precursor
189599
7.39
6%

1105
alpha-2-antiplasmin precursor
54536
5.71
9%

1105
Vitamin D-binding protein precursor
54526
5.4
14%

1105
blood plasma glutamate carboxypeptidase precursor
60349
8.02
5%

1105
ENPP5
54747
5.94
5%

1105
trypsin
27329
5.95
5%

1105
complement component C3
188585
6.02
1%

1105
antithrombin_TRI
5804
4.49
18%

1105
lumican
38717
6.16
15%

1105
alpha 2-plasmin inhibitor
2064
4.53
63%

1105
inter-alpha-trypsin inhibitor
103549
6.51
3%

1105
cAMP-specific phosphodiesterase
84945
5.03
1%

1218
secretoglobin, family 3A member 2
10269
6.71
9%

1218
blood plasma glutamate carboxypeptidase precursor
60349
8.02
3%

1218
alpha-1-antichymotrypsin
48834
5.79
14%

1218
alpha2-HS glycoproteiin
40197
5.43
10%

1244
creatine kinase M
43247
6.63
3%

1244
alpha-1-antichymotrypsin precursor
45567
5.32
26%

1244
alpha2-HS glycoprotein
40197
5.43
16%

1244
plasma glutamate carboxypeptidase
52083
5.79
7%

1244
Chain A, antithrombin Iii
49350
5.95
6%

1244
creatine kinase M
43247
6.63
3%

1244
hornerin
48797
9.71
7%

1244
COMP
85403
4.34
3%

1244
hematopoietic cell-specific Lyn substrate 1

4.74
3%

1244
chondroitin sulfate proteoglycan 2
374585
4.45
0%

1244
nesprin 1 longest
10169979
5.37
1%

1244
Rab3-interacting molecule 2
161216
9.17
0%

1297
ORF
74466
9.49
1%

1297
selenium binding protein
52928
5.93
33%

1297
T-plastin polypeptide
64281
5.73
22%

1297
complement component C3
188585
6.02
4%

1297
PEPD protein
55354
5.64
16%

1297
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
11%

1297
pigment epithelial-differentiating factor
46471
5.84
12%

1297
annexin A2 isoform 2
38808
7.57
6%

1297
cd14 protein precursor
40681
5.84
4%

1297
alpha-2-antiplasmin precursor
54536
5.71
2%

1297
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
3%

1297
phospholipase D3 isoform 2
49196
6
2%

1297
blood plasma glutamate carboxypeptidase precursor
60349
8.02
2%

1297
Chain, The Solution Structure of Reduced monomeric
15954
5.39
13%

Superoxide dismutase

1297
kinesin superfamily protein KIF1B
200459
5.43
4%

1297
lymphoid-restricted membrane protein
56691
5.44
3%

1338
cAMP-specific phosphodiesterase
84945
5.03
1%

1338
phospholipase D3
49196
6
14%

1338
Chain B, alpha-Ferrous-Carbonmonoxy, Beta-Cobaltous-
15971
6.81
32%

Deoxy hemoglobin

1338
annexin A2 isoform
38808
7.57
6%

1338
lysosomal acid phosphatase 2 precursor
48713
6.28
8%

1338
beta-fibrinogen precursor
55545
8.31
7%

1338
hemoglobin alpha-2
15337
8.72
45%

1338
plasma serine protease inhibitor precursor
45886
9.38
13%

1338
hemopexin
13452
6.7
9%

1338
regucalcin
33802
5.89
6%

1338
complement component C4A
194337
6.65
3%

1338
complement component C3
188585
6.02
0%

1338
cAMP-specific phosphodiesterase
84945
5.03
1%

1338
peptidoglycan recognition protein L precursor
68669
7.62
1%

1346
hornerin
48797
9.71
7%

1346
pigment epithelial-differentiating factor
46471
5.84
20%

1346
complement component C3
188585
6.02
5%

1346
glucosamine (N-acetyl)-6-sulfatase precursor
62840
8.6
7%

1346
fibrinogen gamma chain
50077
5.61
12%

1346
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
9%

1346
beta-fibrinogen precursor
55545
8.31
12%

1346
CFI protein
44285
8.49
11%

1346
aldehyde dehydrogenase
51367
5.83
9%

1346
Chain B, T-To-T (High) Quaternary . . .
15975
6.75
15%

1346
phospholipase D3 isoform 2
49196
6
2%

1346
gp180-carboxypeptidase D-like enzyme
153903
5.7
1%

1346
annexin A2 isoform
38808
7.57
14%

1346
regucalcin
33802
5.89
3%

1346
plasma serine protease inhibitor precursor
45886
9.38
6%

1346
fetuin-like protein IRL685
42922
6.87
3%

1387
lactoferrin (unnamed protein)
80228
8.56
1%

1387
coagulation factor X precursor
53870
5.34
16%

1387
ceruloplasmin
116197
5.43
2%

1387
alpha-2-antiplasmin precursor
54536
5.71
4%

1387
complement C4B precursor
189599
7.39
5%

1387
alpha-N-acetylgalatosaminidase
40506
5.34
3%

1387
complement component C3
188585
6.02
2%

1387
serum paraoxonase/arylesterase 1
39895
5.08
6%

1387
antithrombin III
53041
6.32
4%

1387
nesprin 1 isoform longer
1011226
5.37
0%

1397
creatine kinase M
43247
6.63
3%

1397
hemopexin precursor
52254
6.57
12%

1397
Chain B, Alpha-Ferrous-Carbonmonoxy
15971
6.81
31%

1397
annexin A2 precursor
38808
7.57
6%

1414
cAMP-specific phosphodiesterase
84945
5.03
2%

1414
hemopexin precursor
52254
6.57
26%

1414
2-phosphopyruvate-hydratase alpha-enolase
47421
7.01
21%

1414
annexin A2 isoform 2
38808
7.57
8%

1414
alpha 2 macroglobulin
167505
6.06
2%

1414
arylsulfatase B precursor
60195
8.43
3%

1439
complement component C3
188585
6.02
0%

1439
complement component 4 binding protein
29308
5.05
8%

1439
Chain B, Structure of Complement C3b
104912
5.18
4%

1439
protein, alpha1 acid glyco
21433
5.09
9%

1439
complement C4B precursor
189599
7.39
2%

1439
integrin beta-1 precursor
91714
5.3
1%

1447
ankyrin-3
482387
6.12
0%

1447
complement component C3
188585
6.02
7%

1447
Chain B, Crystal Structure of S-Nitroso-Nitrosyl
15922
6.81
53%

Hemoglobin A

1447
annexin A2 isoform 2
38808
7.57
16%

1447
arylsulfatase B precursor
60195
8.43
6%

1447
lysophospholipase 3
46913
6.27
13%

1447
Chain annexin I
35246
7.77
5%

1447
phospholipase D3
49196
6
2%

1503
alpha-fibrinogen precursor
70223
8.26
14%

1503
Chain B, Alpha-Ferrous-Carbonmonoxy
15971
6.81
31%

1503
annexin A2 isoform 2
38808
7.57
16%

1503
neuropolypeptide h3
21027
7.42
20%

1503
glucosamine (N-acetyl0-6-sulfatase precursor
62840
8.6
4%

1503
phospholipase D3 isoform 2
49196
6
4%

1503
Chain E, Structure of Human Transferrin Receptor-
39476
6.41
6%

Transferrin Complex

1503
cAMP-specific phosphodiesterase
84945
5.03
2%

1503
dismutase, Cu/Zn superoxide
16020
8.76
7%

1503
complement component C3
188585
6.02
1%

1503
glutathione transferase M3
27127
5.37
7%

1563
Rho guanine nucleotide exchange factor
223645
5.9
0%

1563
mutant beta-actin
42128
5.22
16%

1563
thrombin inhibitor
42901
5.33
2%

1563
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
6%

1563
complement C4B precursor
189599
7.39
4%

1656
Vitamin D-binding protein precursor
54256
5.4
2%

1656
prepro-C3b/C4B inactivator
68120
7.72
5%

1656
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
11%

1656
annexin A2 isoform 2
38808
7.57
14%

1656
apolipoprotein J precursor
49342
6.27
12%

1656
regucalcin
33802
5.89
12%

1656
phospholipase D3 isoform
49196
6
2%

1656
thrombin inhibitor
42901
5.33
2%

1656
Serpin B8 (Cytoplasmic antiproteinase 2)
43328
5.43
2%

1656
Chain, Glutathione S-Transferase
25729
6.02
12%

1656
inter-alpha-trypsin inhibitor family heavy chain-related
103549
6.51
1%

protein

1656
cAMP-specific phosphodiesterase
84945
5.03
1%

1671
HRX
436238
9.23
0%

1671
antithrombin III
53041
6.32
6%

1671
ectonucleotide pyrophosphatase/phosphodiesterase 5
54745
5.94
2%

1671
alpha2-HS glycoprotein
36268
5.2
2%

1671
creatine kinase M
43247
6.63
3%

1671
cAMP-specific phophodiesterase
84945
5.03
3%

1671
apolipoprotein D
28317
5.14
15%

1671
mitochondrial ribosomal protein L30
18678
10.01
5%

1671
HER2 receptor
141145
5.58
1%

1681
Mucin-16 (Ovarian carcinoma antigen CA125)
2359682
5.65
0%

1681
apolipoprotein J precursor
49342
6.27
24%

1681
complement component C3
188585
6.02
4%

1681
beta-globin types (unnamed protein)
16070
7.12
8%

1681
annexin A2 isoform
38808
7.57
6%

1681
prepro-C3b/C4B inactivator
68120
7.72
4%

1681
regucalcin
33802
5.89
12%

1681
creatine kinase M
43247
6.63
3%

1689
cAMP-specific phophodiesterase
84945
5.03
2%

1689
Chain B, Structure of Complement C3b
104912
5.18
7%

1689
hypothetical protein
53029
5.89
14%

1689
prepro-C3b/C4B inactivator
68120
7.72
1%

1689
regucalcin
33802
5.89
3%

1690
cAMP-specific phophodiesterase
84945
5.03
1%

1690
annexin A2 isoform 2
38808
7.57
22%

1690
transaldolase 1
37688
6.36
13%

1690
Chain B, Cathepsin D
26457
5.31
7%

1690
plasminogen
93263
6.89
1%

1690
Chain A, Crystal Structure of homo sapien glycerol-3-
38401
5.81
5%

phosphate dehydrogenase 1

1690
phosphodiesterase 4D, cAMP-specific . . .
24806
9.88
12%

1690
Chain B, Hemoglobin (Deoxy) Mutant with Val B . . .
15866
6.7
22%

1719
glutathione transferase M3
27127
5.37
4%

1719
apolipoprotein J precursor
49342
6.27
20%

1725
plasminogen
93263
6.89
1%

1725
transaldolase 1
37688
6.36
13%

1725
annexin A2 isoform 2
38808
7.57
22%

1725
Chain B, Alpha-Ferrous-Carbonmonoxy, . . .
15971
6.81
22%

1725
glutathione S-transferase GSTMS-5
25847
6.9
9%

1725
plasminogen
93233
7.04
0%

1737
malate dehydrogenase, mitochondrial precursor
35965
8.92
10%

1737
regucalcin
33802
5.89
27%

1737
immunoglobulin lambda light chain VLJ region
11755
8.62
9%

1737
bridging integrator 3
29703
6.95
4%

1745
cAMP-specific phosphodiesterase
84945
5.03
2%

1745
regucalcin
33802
5.89
17%

1745
apolipoprotein D
28317
5.14
25%

1745
apolipoprotein J precursor
49342
6.27
6%

1745
annexin A2 isoform 2
38808
7.57
6%

1745
antithrombin III
53041
6.32
8%

1745
Rho guanine nucleotide exchange factor
223645
5.9
2%

1747
alpha2-HS glycoprotein
36268
5.2
2%

1747
apolipoprotein D
28317
5.14
20%

1747
regucalcin
4759036
5.89
11%

1747
annexin A2, isoform
32600
5.93
9%

1747
apolipoprotein J precursor
49342
6.27
4%

1757
cAMP-specific phosphodiesterase
84945
5.03
1%

1757
regucalcin
33802
5.89
11%

1757
protein, alpha1 acid glyco
21443
5.09
4%

1757
apolipoprotein J precursor
49342
6.27
6%

1757
cAMP-specific phosphodiesterase
84945
5.03
1%

1757
annexin A2 isoform 2
38808
7.57
3%

1778
aberrant LSLCL
33536
6.82
6%

1778
annexin A2 isoform 2
38808
7.57
43%

1778
Chain, Annexin Family Mol_—
36480
5.63
13%

1778
ficolin 3 isoform 1 precursor
66198
6.2
9%

1778
alpha-fibrinogen precursor
70223
8.26
4%

1778
Chain B, Cathepsin D
26457
5.31
7%

1778
plasminogen
93233
7.04
0%

1778
cAMP-specific phosphodiesterase PDE4D5
84945
5.03
1%

1778
actin related protein2/3
34426
6.84
3%

1778
basic helix-loop-helix domain containing
23935
9.37
3%

1778
mitochondrial ribosomal protein S34
25692
9.98
3%

1778
Bruton's agammaglobulinemia tyrosine kinase
76625
8.05
1%

1781
ubinuclein
122036
9.37
2%

1781
Chain, Human Annexin V with Proline substitution by
36041
4.94
19%

Thioproline

1781
annexin A2 isoform 2
38808
7.57
18%

1781
Chain, Annexin Family Mol_—
36480
5.63
6%

1781
cathepsin Z precursor
34544
6.7
3%

1781
complex-forming glycoprotein HC
20592
5.84
11%

1781
apolipoprotein J precursor
49342
6.27
5%

1781
cAMP-specific phosphodiesterase
84945
5.03
1%

1781
bromodomain adjacent to zinc finger domain 2B
222440
5.95
1%

1783
mitochondrial ribosomal protein L30
18678
10.01
10%

1783
annexin A2 isoform 2
38808
7.57
27%

1783
Chain, Annexin Family Mol
36480
5.63
16%

1783
alpha-fibrinogen precursor
70223
8.26
2%

1783
annexin II cell-surface form = cytomegalovirus binding
2160
5.8
100%

protein

1783
Chain B, Cathepsin D
26457
5.31
7%

1783
Chain, Annexin I
35246
7.77
5%

1783
apolipoprotein J precursor
49342
6.27
6%

1783
glutathione transferase M3
27127
5.37
4%

1783
truncated putative T7-like mitochondrial DNA helicase
66430
8.33
5%

1783
cAMP-specific posphodiesterase
84945
5.03
1%

1783
alpha-2-macroglobulin precursor
164600
6
0%

1791
Chain A, Hr1b Domain From Prk1
9054
9.77
11%

1791
annexin A2 isoform 2
38808
7.57
32%

1791
Chain, Annexin Family Mol_—. . .
36480
5.63
13%

1791
Chain, Annexin I
35246
7.77
7%

1791
annexin II cell-surface form = . . .
2160
5.8
100%

1791
complement C4B precursor
189599
7.39
2%

1865
Chain B, Cathepsin D
26457
5.31
7%

1865
protein PP4-X (annexin variant)
36262
5.65
18%

1868
cAMP-specific phosphodiesterase
84945
5.03
4%

1868
protein PP4-X (annexin A4 variable)
36262
5.65
26%

1868
apolipoprotein E
36302
5.65
5%

1868
Chain B, Crystal Structure of S-Nitroso-Nitrosyl Human
15922
6.81
23%

hemoglobin A

1868
regucalcin
33802
5.89
10%

1868
protein disulfide isomerase-related protein 5

4.95
2%

1868
cathepsin Z precursor
34544
6.7
3%

1868
serine (or cysteine) proteinase inhibitor
42829
5.9
1%

1868
Chain C, X-Ray Crystal Structure of Cyclophilin AHIV-1 . . .
16178
5.94
4%

1868
Chain A, Crystal Structure of Human Tr . . .
30705
5.41
4%

1868
coiled-coil domain containing 96
62958
4.92
1%

1915
immunoglobulin lambda light chain VLJ region . . .
11755
8.62
9%

1915
T-plastin polypeptide (actin crosslinking)
64281
5.73
12%

1915
Chain A, Crystal Structure of Lipid-Free Human
28061
5.27
44%

Apolipoprotein A-I

1915
nuclear chloride channel
27249
5.02
20%

1915
regucalcin
33802
5.89
18%

1915
inositol-1-monophosphatase
26813
5.74
10%

1915
Chain B, T-To-T Quaternary Transitions . . .
15927
6.75
30%

1915
thrombin inhibitor
42901
5.33
3%

1915
UCC1 protein (mammalian ependymin protein)
20162
5.03
6%

1915
ectonucleotide pyrophosphatase/phosphodiesterase
54745
5.94
1%

1915
glutathione S-transferase
25847
6.9
11%

1915
complement C4B precursor
189599
7.39
3%

1915
protein disulfide isomerase-related protein 5
46512
4.95
2%

1915
complex-forming glycoprotein HC
20592
5.84
7%

1915
Chain A, Hemoglobin Thionville Alpha Chain Mutant . . .
15446
7.82
23%

1915
Chain B, Cathepsin D
26457
5.31
7%

1915
gelsolin isoform a precursor
86043
5.9
1%

1915
albumin, isoform CRA_a
25732
6.45
3%

1915
heat shock 70 kDa protein 8 isoform 1
71082
5.37
1%

1915
serpin pieptidase inhibitor, clade I . . .
46287
5.08
6%

1915
cAMP-specific phosphodiesterase
84945
5.03
2%

1915
complement factor B
86819
6.55
0%

1915
heat shock protein
70237
5.56
1%

1915
cathepsin F
38244
6.54
2%

1938
thrombospondin-4
108415
4.44
1%

1938
apolipoprotein D
28317
5.14
29%

1938
78 kDa glucose regulated protein precursor
72492
5.07
8%

1938
L-plastin
70815
5.2
8%

1938
heat shock 70 kDa protein 8 isoform 1
71082
5.37
6%

1938
Chain B, Crystal Structure of S-Nitroso-Nirosyl Human
15922
6.81
23%

Hemoglobin A

1938
beta-trace protein, prostaglandin D synthase
18898
6.95
4%

1938
glutathione transferase M3
27127
5.37
4%

2029
creatine kinase M
43247
6.63
7%

2029
heat shock 70 kDa protein 8 isoform 1
71082
5.37
8%

2029
heat shock protein
70237
5.56
9%

2029
GRP78 (78 kDa glucose-regulated protein precursor)
72185
5.03
7%

2029
proapolipoprotein
28944
5.45
20%

2029
glutathione transferase M3
27127
5.37
4%

2029
Chain A, Human Aspartylglucosaminidase
17552
4.82
4%

2029
HSPC336 (apolipoprotein M)
21220
6.48
3%

2052
cAMP-specific phosphodiesterase
84945
5.03
2%

2052
heat shock 70 kDa protein 8 isoform
71082
5.37
7%

2052
heat shock protein
70237
5.56
7%

2052
GRP78 precursor (78 kDa glucose-regulated protein
72185
5.03
5%

precursor

2052
lipoprotein Gln I
28329
5.27
16%

2052
albumin, isoform CRA_t
60211
6.66
3%

2052
glutathione transferase M3
27127
5.37
11%

2052
beta-trace protein, prostaglandin D synthase
18898
6.95
4%

2068
plasminogen
93263
6.89
1%

2068
Chain A, Human aspartylglucosaminidase
17552
4.82
9%

2068
78 kDa glucose-regulated protein precursor
72492
5.07
6%

2068
heat shock 70 kDa protein 8 isoform 1
71082
5.37
2%

2068
cAMP--specific phosphodiesterase
84945
5.03
1%

2090
proapolipoprotein
28944
5.45
3%

2090
Chain B, Non-Covalent Complex Between Alpha-1-Pi . . .
26077
8.23
51%

2090
Chain C, Globular Head of the Complement System Protein
14451
8.85
25%

C1q

2090
putative acrosin-like protease
25468
9.09
6%

2090
2′,′3′-cyclic-nucleotide 3′-phosphodiesterase
45469
8.73
4%

2090
Chain A, Trypsin
24669
7.64
4%

2090
alpha-fibrinogen precursor
70223
8.26
2%

2090
glutathione transferase A5
25763
7.74
6%

2090
inter-alpha-trypsin inhibitor
93745
6.02
1%

2090
collagen alpha 1
70610
9.18
2%

2090
immunoglobulin lambda-chain
13716
7.71
10%

2090
cAMP-specific phosphodiesterase
84945
5.03
4%

2146
potassium channel, subfamily K, member 18
44498
6.6
1%

2146
glutathione peroxidase 3 precursor
25774
8.2
27%

2146
human basement membrane heparan sulfate proteoglycan
479812
6.1
0%

core protein

2146
mitochondrial ribosomal protein L30
18678
10.01
5%

2146
calcium channel beta-2 chain
53073
9.3
4%

2180
cAMP-specific phosphodiesterase
84945
5.03
1%

2180
glucosamine-phosphate N-acetyltransferase 1
21078
8.17
21%

2180
neuropolypeptide h3
21027
7.42
26%

2180
preproacrosin
46455
9.2
3%

2180
cAMP-specific phosphodiesterase
84945
5.03
4%

2208
axonemal dynein light chain 1
17256
5.32
5%

2208
Chain B, T-To-T(High) Quaternary Transitions
15911
6.75
28%

2208
cytoplasmic phosphotyrosyl protein phosphatase
18091
7.04
12%

2208
Chain, The Solution Structure of Reduced Monomericc
15954
5.39
13%

Superoxide Dismutase

2208
Chain B, Crystal Structure of A Rac-Rhogdi Complex
20521
6.16
8%

2208
albumin, isoform CRA_b
61122
6.96
4%

2215
plasminogen
93263
6.89
1%

2215
DOK6 protein (docking protein 5-like
31492
5.9
4%

2215
dermcidin preproprotein
11391
6.08
10%

2235
shroom family member 3 protein
218190
7.87
3%

2235
aspartylglucosaminidase alpha subunit (N-terminal)
2177
8.53
40%

2235
ubiquitin-conjugating enzyme 9
18146
8.67
5%

TABLE 5

27
alpha-2-macroglobulin precursor

76
fibronectin precursor, Chain B, Structure of complement C3b, C9

complement protein

93
no proteins meet the criteria

124
unnamed protein (coagulation factor II precursor)

206
alpha-1-antichymotrypsin

210
alpha-2-macroglobulin precursor, complement component C3, complement

factor H

246
alpha-2-macroglobulin precursor, complement factor H

255
macroglobulin alpha2, complement factor H

265
No proteins meet criteria

292
alpha-2-macroglobulin precursor, complement factor H, trypsin inhibitor,

inter-alpha-trypsin heavy chain H1 precursor

372
alpha-2-macroglobulin precursor, complement factor H isoforma precursor,

gelsolin isoform a precursor

384
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

385
phosphatidylinositol-glycan-specific phospholipase D1 precursor,

ceruloplasmin, inter-alpha-trypsin inhibitor family heavy chain-related

protein

393
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

394
inter-alpha-trypsin inhibitor heavy chain H4 precursor, ceruloplasmin

408
glycosylphosphatidylinositol specific phosphatase D1, ceruloplasmin

477
alpha-2-macroglobulin precursor, complement component C6 precursor

peptide, complement factor B

481
pre-pro-alpha(I) collagen

495
Ceruloplasmin, complement component C3, factor H, SERPIN2 protein, gp-

180-carboxypeptidase D-like enzyme

496
inter-alpha-trypsin inhibitor family heavy chain-related protein, Chain B, Human

Complement Component C3, alpha-2-macroglobulin precursor, ceruloplasmin

644
Fibulin-1 isoform D precursor, inter-alpha-trypsin inhibitor family heavy

chain-related protein, plasminogen, complement factor B, HGF activator,

preproprotein

746
unnamed protein (coagulation factor II precursor), afamin precursor,

Vitamin K-dependent protein, complement component 1, s subcomponent,

iinter-alpha-trypsin inhibitor, ASPIC

805
complement component 3 precursor, plasma kallikrein precursor, annexin

A2 isoform 2

840
glucosamine (N-acetyl)-6-sulfatase precursor, unnamed protein (cystic

fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding

protein A9

849
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII A

chain precursor, peptidoglycan recognition protein L precursor, complement

component 4 binding protein

856
inter-alpha-trypsin inhibitor heavy chain H1 precursor, glucosamine (N-

acetyl)-6-sulfatase precursor, fibrinogen gamma chain, coagulation factor

XIII A chain precursor

864
glucosamine (N-acetyl)-6-sulfatase precursor, Ig mu chain precursor,

phospholipase D3 isoform, moesin

962
complement 9, Chain B, Structure of Complement C3b, alpha-2-antiplasmin

precursor, kininogen, thrombin inhibitor

973
complement 9, Chain A, antithrombin Iii, alpha-2-antiplasmin precursor,

kinninogen, thrombin inhibitor, L-plastin, complement component 1, alpha-

1-B-glycoprotein, hemopexin precursor

1472
complement component C4A, complement component C3, apolipoprotein

A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin,

COMP, serpin peptidase inhibitor, clade I, follistatin-like 1 precursor

1498
complement factor H-related protein 1 precursor, Chain A, Crystal Structure

of Lipid-Free human Apolipoprotein A-1, annexin A2 isoform 2,

phospholipase D3 isoform 2, Chain E, Structure of human transferring

receptor-transferrin complex

44
fibronectin precursor, complement component C3, alpha-2-macroglobulin

precursor

82
Chain B, Structure of Complement C3b

109
factor H, fibronectin precursor

126
fibronectin 1 isoform 3 preproprotein, alpha-2-macroglobulin precursor,

164
macroglobulin alpha 2

184
alpha-2-macroglobulin

191
alpha-2-macroglobulin, complement component C3

205
no protein matches criteria

216
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

244
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

252
alpha 2 macroglobulin, complement factor H, complement component C3

267
inter-alpha-trypsin inhibitor, Human Factor H, fibronectin precursor, inter-

alpha-trypsin inhibitor, C-terminal

295
complement factor H, alpha 2 macroglobulin, trypsin inhibitor, inter-alpha-

trypsin inhibitor

352
complement factor H, alpha 2 macroglobulin, inter-alpha-trypsin inhibitor,

trypsin inhibitor, complement component C3

392
Ceruloplasmin, phosphatidylinositol-glycan-specific phospholipase D1

396
afamin precursor, ceruloplasmin, inter-alpha-trypsin inhibitor

469
complement component 6, isoform CRA_b

509
inter-alpha-trypsin inhibitor heavy chain-related protein, ceruloplasmin,

Chain B, Structure of Complement C3b

510
ceruloplasmin (ferroxidase), Chain A, Crystal Structure of human Galectin-7

512
ceruloplasmin (ferroxidase), inter-alpha-trypsin inhibitor family heavy

chain-related protein

547
serum albumin, inter-alpha-trypsin inhibitor family heavy chain-related

protein

533
COMP, ceruloplasmin

554
inter-alpha-trypsin inhibitor family heavy chain-related protein

555
ALB protein, gelsolin isoform a precursor

561
serum albumin, trypsin inhibitor, complement component C3

567
Chain B, Human complement component C3

568
complement component C3, complement factor B, gelsolin isoform

precursor

655
Ceruloplasmin (ferroxidase), fibulin-1 isoform D precursor, hypothetical

protein (inter-alpha-globulin inhibitor H4), valosin-containing protein,

Vitamin D-binding protein precursor

677
unnamed protein (complement component 2 precursor), annexin A2,

complement factor B

701
Annexin A2 isoform 2

703
inter-alpha-trypsin inhibitor family heavy chain-related protein,

ceruloplasmin (ferroxidase)

704
hornerin precursor

712
complement component 1, s subcomponent, ASPIC, afamin precursor,

Vitamin K-dependent protein

729
plasma kallikrein precursor, S100 calcium-binding protein A9, Protein

S100-A7 (psoriasin)

744
gelsolin isoform a precursor

745
gelsolin isoform a precursor

748
gelsolin isoform a precursor, coagulation factor XIII, Chain b, Alpha-

Ferrous-Carbonmonoxy

763
afamin precursor, coagulation factor II precursor, insulin-like growth factor

binding protein, acid labile, histidine-rich glycoprotein precursor,

phospholipid transfer protein isoform a precursor, antithrombin III

764
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII B

chain, gelsolin isoform a precursor

765
ASPIC, coagulation factor II precursor (unnamed protein), vitronectin

(unnamed protein), histidine-rich glycoprotein precursor, biotinidase

precursor

766
afamin precursor, insulin-like growth factor binding protein, acid labile

subunit, coagulation factor II precursor, alpha-1-B-glycoprotein, thrombin

inhibitor, C9 complement protein

770
Coagulation factor XIII B chain precursor

776
insulin-like growth factor binding protein, hemopexin precursor

818
vanin 1 precursor, biotinidase precursor, vitronectin (unnamed protein),

ASPIC

825
extracellular matrix protein 1 isoform precursor, hemopexin precursor,

histidine-rich glycoprotein, dopamine beta-hydroxylase precursor,

peptidoglycan recognition protein L precursor

827
Chain A, Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma

chain, hemopexin precursor

833
Extracellular matrix protein1 isoform 1 precursor, inter-alpha (globulin)

inhibitor H1, isoform CRA_b, hemopexin precursor

844
alpha-1-B-glycoprotein, alpha-2-antiplasmin precursor, complement

component 1, vitronectin precursor (unnamed protein), Vitamin K-

dependent protein S precursor, ASPIC

846
Vitamin K-dependent protein S precursor,

Chain B, Human Complement Component C3, coagulation factor (unnamed

protein), complement 9, GRP78, afamin precursor

TABLE 6

27
alpha-2-macroglobulin precursor

76
fibronectin precursor, Chain B, Structure of complement C3b, C9

complement protein

93
no proteins meet the criteria

124
unnamed protein (coagulation factor II precursor)

206
alpha-1-antichymotrypsin

210
alpha-2-macroglobulin precursor, complement component C3, complement

factor H

246
alpha-2-macroglobulin precursor, complement factor H

255
macroglobulin alpha2, complement factor H

265
No proteins meet criteria

292
alpha-2-macroglobulin precursor, complement factor H, trypsin inhibitor,

inter-alpha-trypsin heavy chain H1 precursor

372
alpha-2-macroglobulin precursor, complement factor H isoforma precursor,

gelsolin isoform a precursor

384
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

385
phosphatidylinositol-glycan-specific phospholipase D1 precursor,

ceruloplasmin, inter-alpha-trypsin inhibitor family heavy chain-related

protein

393
Ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 precursor,

phosphatidylinositol-glycan-specific phospholipase D1 precursor

394
inter-alpha-trypsin inhibitor heavy chain H4 precursor, ceruloplasmin

408
glycosylphosphatidylinositol specific phosphatase D1, ceruloplasmin

477
alpha-2-macroglobulin precursor, complement component C6 precursor

peptide, complement factor B

481
pre-pro-alpha(I) collagen

495
Ceruloplasmin, complement component C3, factor H, SERPIN2 protein, gp-

180-carboxypeptidase D-like enzyme

496
inter-alpha-trypsin inhibitor family heavy chain-related protein, Chain B,

Human Complement Component C3, alpha-2-macroglobulin precursor,

ceruloplasmin

644
Fibulin-1 isoform D precursor, inter-alpha-trypsin inhibitor family heavy

chain-related protein, plasminogen, complement factor B, HGF activator,

preproprotein

746
unnamed protein (coagulation factor II precursor), afamin precursor,

Vitamin K-dependent protein, complement component 1, s subcomponent,

iinter-alpha-trypsin inhibitor, ASPIC

805
complement component 3 precursor, plasma kallikrein precursor, annexin

A2 isoform 2

840
glucosamine (N-acetyl)-6-sulfatase precursor, unnamed protein (cystic

fibrosis antigen), ezrin (p81) (cytovillin) (villin-2), S100 Calcium binding

protein A9

849
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII A

chain precursor, peptidoglycan recognition protein L precursor, complement

component 4 binding protein

856
inter-alpha-trypsin inhibitor heavy chain H1 precursor, glucosamine (N-

acetyl)-6-sulfatase precursor, fibrinogen gamma chain, coagulation factor

XIII A chain precursor

864
glucosamine (N-acetyl)-6-sulfatase precursor, Ig mu chain precursor,

phospholipase D3 isoform, moesin

962
complement 9, Chain B, Structure of Complement C3b, alpha-2-antiplasmin

precursor, kininogen, thrombin inhibitor

973
complement 9, Chain A, antithrombin Iii, alpha-2-antiplasmin precursor,

kinninogen, thrombin inhibitor, L-plastin, complement component 1, alpha-

1-B-glycoprotein, hemopexin precursor

1472
complement component C4A, complement component C3, apolipoprotein

A-IV precursor, serum paraoxonase/arylesterase, preprohaptoglobulin,

COMP, serpin peptidase inhibitor, clade I, follistatin-like 1 precursor

1498
complement factor H-related protein 1 precursor, Chain A, Crystal Structure

of Lipid-Free human Apolipoprotein A-1, annexin A2 isoform 2,

phospholipase D3 isoform 2, Chain E, Structure of human transferring

receptor-transferrin complex

44
fibronectin precursor, complement component C3, alpha-2-macroglobulin precursor

82
Chain B, Structure of Complement C3b

109
factor H, fibronectin precursor

126
fibronectin 1 isoform 3 preproprotein, alpha-2-macroglobulin precursor,

164
macroglobulin alpha 2

191
complement component C3

205
no protein matches criteria

216
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

244
collagen type IV alpha 1, alpha 2 type IV collagen preproprotein

252
alpha 2 macroglobulin, complement factor H, complement component C3

267
inter-alpha-trypsin inhibitor, Human Factor H, fibronectin precursor, inter-

alpha-trypsin inhibitor, C-terminal

295
complement factor H, alpha 2 macroglobulin, trypsin inhibitor, inter-alpha-

trypsin inhibitor

352
complement factor H, alpha 2 macroglobulin, inter-alpha-trypsin inhibitor,

trypsin inhibitor, complement component C3

392
Ceruloplasmin, phosphatidylinositol-glycan-specific phospholipase D1

396
afamin precursor, ceruloplasmin, inter-alpha-trypsin inhibitor

469
complement component 6, isoform CRA_b

509
inter-alpha-trypsin inhibitor heavy chain-related protein, ceruloplasmin,

Chain B, Structure of Complement C3b

510
Chain A, Crystal Structure of human Galectin-7

512
inter-alpha-trypsin inhibitor family heavy chain-related protein

547
serum albumin, inter-alpha-trypsin inhibitor family heavy chain-related

protein

533
COMP, ceruloplasmin

554
inter-alpha-trypsin inhibitor family heavy chain-related protein

555
ALB protein, gelsolin isoform a precursor

561
serum albumin, trypsin inhibitor, complement component C3

567
Chain B, Human complement component C3

568
complement component C3, complement factor B, gelsolin isoform

precursor

655
fibulin-1 isoform D precursor, hypothetical protein (inter-alpha-globulin

inhibitor H4), valosin-containing protein, Vitamin D-binding protein

precursor

677
unnamed protein (complement component 2 precursor), annexin A2,

complement factor B

701
Annexin A2 isoform 2

703
inter-alpha-trypsin inhibitor family heavy chain-related protein

704
hornerin precursor

712
complement component 1, s subcomponent, ASPIC, afamin precursor,

Vitamin K-dependent protein

729
plasma kallikrein precursor, S100 calcium-binding protein A9, Protein

S100-A7 (psoriasin)

744
gelsolin isoform a precursor

745
gelsolin isoform a precursor

748
gelsolin isoform a precursor, coagulation factor XIII, Chain b, Alpha-

Ferrous-Carbonmonoxy

763
afamin precursor, coagulation factor II precursor, insulin-like growth factor

binding protein, acid labile, histidine-rich glycoprotein precursor,

phospholipid transfer protein isoform a precursor, antithrombin III

764
glucosamine (N-acetyl)-6-sulfatase precursor, coagulation factor XIII B

chain, gelsolin isoform a precursor

765
ASPIC, coagulation factor II precursor (unnamed protein), vitronectin

(unnamed protein), histidine-rich glycoprotein precursor, biotinidase

precursor

766
afamin precursor, insulin-like growth factor binding protein, acid labile

subunit, coagulation factor II precursor, alpha-1-B-glycoprotein, thrombin

inhibitor, C9 complement protein

770
Coagulation factor XIII B chain precursor

776
insulin-like growth factor binding protein, hemopexin precursor

818
vanin 1 precursor, biotinidase precursor, vitronectin (unnamed protein),

ASPIC

825
extracellular matrix protein 1 isoform precursor, hemopexin precursor,

dopamine beta-hydroxylase precursor, peptidoglycan recognition protein L

precursor

827
Chain A, Crystal Structure of Native Heparin Cofactor Ii, fibrinogen gamma

chain, hemopexin precursor

833
Extracellular matrix protein1 isoform 1 precursor, inter-alpha (globulin)

inhibitor H1, isoform CRA_b, hemopexin precursor

844
alpha-1-B-glycoprotein, alpha-2-antiplasmin precursor, complement

component 1, vitronectin precursor (unnamed protein), Vitamin K-

dependent protein S precursor, ASPIC

846
Vitamin K-dependent protein S precursor, Chain B, Human Complement

Component C3, coagulation factor (unnamed protein), complement 9,

GRP78, afamin precursor

PROTEIN BIOMARKERS AND THERAPEUTIC TARGETS FOR OSTEOARTHRITIS

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