METHODS FOR THE MATURATION OF CARDIOMYOCYTES ON AMNIOTIC FLUID CELL-DERIVED ECM, CELLULAR CONSTRUCTS, AND USES FOR CARDIOTOXICITY AND PROARRHYTHMIC SCREENING OF DRUG COMPOUNDS

FIELD

The disclosure generally relates to the use of cellular constructs of cardiomyocytes derived from human stem cells on cell-derived extracellular matrices, methods of making the constructs, and methods for cardiotoxicity and proarrhythmic screening assays of drug compounds using the constructs.

BACKGROUND

Cardiotoxicity, or the perceived potential for cardiotoxicity, is a leading cause of toxicity related drug attrition during the investigation and selection of new drugs. Cardiac safety testing of new chemical entities that become lead drug candidates is a critical aspect of the drug discovery and development pipeline. A large number of cardiac side effects of cardiac and non-cardiac drugs are caused by drug interaction with one or more cardiac ion channels. Cardiac ion channels regulate cellular excitability, contractility and overall cardiac performance, and alteration of cardiac ion channel function can lead to sudden cardiac death. This contributed to the release of drug candidate testing guidelines from The International Conference on Harmonization (ICH).

The current preclinical drug candidate testing guidelines from the IHC (ICH S7A and S7B-Pharmacology Studies) rely on genetically modified heterologous cells and in vivo animal models. It has become increasingly recognized that these studies, such as hERG assay and QT prolongation studies, do not accurately predict cardiotoxicity and proarrhythmia risk for humans. Since 2005, cardiac safety of a drug compound has been determined almost exclusively by its effect or potential effect on the QT interval of the electrocardiogram (ECG) or the action potential duration (APD), and the potential to lead to a life-threatening arrhythmia called Torsades de Pointes (TdP). However, QT prolongation is not the ideal indicator for TdP as drugs that prolong the QT interval do not always cause TdP. It is now recognized that the QT prolongation parameter is only a surrogate marker for proarrhythmia. Data from pre-clinical and clinical trials have shown that there is no fixed relationship between the magnitude of QT prolongation and the risk for development of fatal arrhythmias such as TdP.

Therefore, the US Food and Drug Administration (FDA) and other stakeholders in drug discovery have called for an evolution in pre-clinical cardiotoxicity testing. The proposed new paradigm is called the Comprehensive In-Vitro Proarrhythmia Assay (CiPA). An integral part of the CiPA Initiative (cipaproject.org/) includes incorporation of data collected from human stem cell derived cardiomyocytes for cardiotoxicity and proarrhythmia assays. The overall goal of these new proposed guidelines is to provide a more accurate and comprehensive mechanistic based assessment of proarrhythmic potential that would more accurately assess the risk of new drugs. In review of the proposed CiPA Initiative's guidelines, the FDA has defined two advances that must be made before human cardiomyocytes can be incorporated in the new initiative. First, the growth and maturation state of human stem cell derived cardiomyocytes needs to be advanced to more closely resemble the structure and function of adult human cardiomyocytes. Second, a reliable high throughput screening platform using these cells must be developed.

There are generally three types of systems currently utilized to evaluate the electrophysiology of cardiomyocytes in vitro: 1) Patch clamping systems; 2) micro-electrode array (MEA) systems; and 3) voltage sensitive dye (VSD) visualization methods. Manual patch clamping systems are most commonly used in very early research studies to evaluate the electrophysiology of individual cells. These devices, while providing accurate and sensitive ionic current measurements, cannot be used for in vitro cell systems that more closely mimic cell-cell interaction in cardiac tissue. MEA systems include electrodes that are incorporated into cell culture wells allowing for the measurement of current across the well. While allowing for high throughput analysis and ability to measure impedance in in vitro cell systems, these systems have low spatial resolution, do not provide data on action potential shape, and hinder direct visualization of the cells and the ability to assess 3-D culture systems that more closely mimic cardiac tissue architecture. VSD systems are gaining interest as they address many of the shortcomings of the current technologies described above with features that include: 1) allowing for high throughput analysis; 2) providing high spatial resolution; 3) allowing visualization of impulse propagation across a culture dish; and 4) allowing for modification of the culture conditions including addition of extracellular matrix leading to a more natural testing environment.

The use of cardiomyocytes derived from human stem cells, such as induced pluripotent stem cells, have had limited success to date in cardiotoxicity and proarrhythmic assay screening. Cardiomyocytes derived from induced human pluripotent stem cells (hiPSC-CMs) are commercially available and can be purchased from several companies in cryopreserved vials that can be thawed and plated as monolayers. These hiPSC-CMs can be made in large scale in vitro. Also, hiPSC-CMs can be obtained from patient specific hiPSCs for a specific individual. However, there are hurdles that still need to be overcome to make the hiPSC-CMs a meaningful part of the new CiPA Initiative paradigm. 1) The maturation of hiPSC-CM structure and function must be advanced. Notably, the Kir2.1 potassium channel is absent in currently available hiPSC-CMs and sodium channel expression is low. Currently available hiPSC-CMs are very immature functionally and structurally. The vast majority of currently used hiPSC-CM-based proarrhythmia screening assays rely on immature, fetal-like cells that do not resemble the structure of function of the adult cardiomyocyte. 2) Electrical pacing of hiPSC-CM monolayers in a high throughput electrophysiological screening platform is needed. The vast majority of current hiPSC-CM-based proarrhythmia screens rely solely on field potential duration (MEA technology) or action potential duration prolongation (VSD technology) as surrogate marker for TdP induction. This is a limitation because not all drugs that prolong the action potential (QT interval) will cause fatal TdP arrhythmias. Although certain maturation states of immature hiPSC-CMs have been achieved using Matrigel™ ECM and bone-marrow cell-derived ECM in culture, use of these hiPSC-CMs in proarrhythmia screening assays did not produce consistent results in the observation of arrhythmia activation patters consistent with what is known to occur in cases of TdP in humans, especially between low risk and high risk drugs.

Thus, advanced materials and new methods are needed for the precise assessment and screening of the cardiac safety liability of drug compounds for accurate, reliable and efficient development of new drug candidates.

SUMMARY

The present disclosure provides a solution to at least some of the aforementioned limitations and deficiencies in the art relating to the assessment and screening of the cardiac safety liability of drug candidates. The solution is premised on the discovery of an extracellular matrix derived from cells isolated from amniotic fluid (AFC-ECM), which can be used for the maturation of human stem cell derived cardiomyocytes. These mature cardiomyocytes can then be used in a cellular construct with the AFC-ECM for cardiotoxicity and proarrhythmic testing of drugs.

In one aspect, disclosed is a method for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells, the method comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) contacting the immature hiPSC-CMs with the AFC-ECM; and (d) culturing the immature hiPSC-CMs with the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs, thereby forming mature cardiomyocytes; wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments the mature cardiomyocytes have a similar or the same morphology as illustrated in any one of FIGS. 6 to 14. In some embodiments, the immature hiPSC-CMs are plated on the AFC-ECM. In some embodiments, the mature cardiomyocytes form as a monolayer on the AFC-ECM, thereby forming a cellular construct comprising a monolayer of mature cardiomyocytes on the AFC-ECM, wherein the mature cardiomyocytes are aligned on the AFC-ECM. In some embodiments, the immature hiPSC-CMs do not express inward-rectifier potassium channel Kir2.1. In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

In another aspect, disclosed is a cellular construct comprising a monolayer of mature cardiomyocytes on an extracellular matrix derived from cells isolated in vitro from amniotic fluid (AFC-ECM), wherein the mature cardiomyocytes are AFC-ECM cultured cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), and wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments the mature cardiomyocytes have a similar or the same morphology as illustrated in any one of FIGS. 6 to 14. In some aspects, the mature cardiomyocytes include the inward-rectifier Kir2.1 potassium channel and/or express inward-rectifier potassium channel Kir2.1. In certain aspects, the mature cardiomyocytes can be matured from immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture on the AFC-ECM, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure (striped appearance) resembling adult human cardiac tissue. In some embodiments, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In some embodiments, fiber tracks are present on the construct. In some embodiments, the AFC-ECM comprises laminin, collagen alpha-1 (XVIII), basement membrane-specific heparan sulfate proteoglycan core protein, agrin, vimentin, and collagen alpha-2 (IV), and/or isoforms thereof. In some embodiments, the isoform of collagen alpha-1 (XVIII) is isoform 2. In some embodiments, the isoform of agrin is isoform 6. In some embodiments, the AFC-ECM further comprises fibronectin and/or an isoform thereof. In some embodiments, the AFC-ECM does not contain decorin, perlecan, and/or collagen (III). In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

In another aspect, disclosed is a method for making a cellular construct of mature cardiomyocytes on an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM), the method comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; and (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming the cellular construct, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments the mature cardiomyocytes have a similar or the same morphology as illustrated in any one of FIGS. 6 to 14. In some embodiments, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In some embodiments, fiber tracks are present on the cellular construct. In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

In another aspect, disclosed is a method for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro, the method comprising contacting the drug compound with the mature cardiomyocytes of any one of the cellular constructs disclosed throughout the specification, and observing for a change in the electrophysiology of the mature cardiomyocytes to confirm whether the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes. A change in the electrophysiology of the mature cardiomyocytes confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes. The changes in the electrophysiology of the mature cardiomyocytes can include, but are not limited to, APD prolongation, APD prolongation plus rotors, and/or various types of arrhythmias, such as tachyarrhythmia (TA), quiescence (Q), delayed afterdepolarization (DAD), and/or early afterdepolarization (EAD). Observations can also include the cell viability, cell density, and/or morphology of the cells. In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is prolongation of action potential duration (APD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is early after depolarization (EAD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is delayed after depolarization (DAD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is action potential duration prolongation (APD prolongation) plus rotors. In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is an arrhythmia. In some aspects, the cellular construct can be prepared by a process comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; and (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming a cellular construct, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments the mature cardiomyocytes have a similar or the same morphology as illustrated in any one of FIGS. 6 to 14. In one embodiment, the immature hiPSC-CMs do not express inward-rectifier potassium channel Kir2.1. In another embodiment, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In another embodiment, fiber tracks are present on the cellular construct. In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

Also, disclosed in the context of the present invention are the following embodiments 1 to 20.

Embodiment 1 is a method for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells, the method comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) contacting the immature hiPSC-CMs with the AFC-ECM; and (d) culturing the immature hiPSC-CMs with the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs, thereby forming mature cardiomyocytes; wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue.

Embodiment 2 is the method of embodiment 1, wherein the immature hiPSC-CMs are plated on the AFC-ECM.

Embodiment 3 is the method of any one of embodiments 1 or 2, wherein the mature cardiomyocytes form as a monolayer on the AFC-ECM, thereby forming a cellular construct comprising a monolayer of mature cardiomyocytes on the AFC-ECM, wherein the mature cardiomyocytes are aligned on the AFC-ECM.

Embodiment 4 is the method of any one of embodiments 1 to 3, wherein the immature hiPSC-CMs do not express inward-rectifier potassium channel Kir2.1.

Embodiment 5 is a cellular construct comprising a monolayer of mature cardiomyocytes on an extracellular matrix derived from cells isolated in vitro from amniotic fluid (AFC-ECM), wherein the mature cardiomyocytes are AFC-ECM cultured cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), and wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue.

Embodiments 6 is the cellular construct of embodiment 5, wherein the monolayer of mature cardiomyocytes is aligned on the AFC-ECM.

Embodiment 7 is the cellular construct of any one of embodiments 5 or 6, wherein fiber tracks are present on the construct.

Embodiment 8 is the cellular construct of any one of embodiments 5 to 7, wherein the AFC-ECM comprises laminin, collagen alpha-1 (XVIII), basement membrane-specific heparan sulfate proteoglycan core protein, agrin, vimentin, and collagen alpha-2 (IV), and/or isoforms thereof.

Embodiment 9 is the cellular construct of embodiment 8, wherein the isoform of collagen alpha-1 (XVIII) is isoform 2, and/or wherein the isoform of agrin is isoform 6.

Embodiment 10 is the cellular construct of any one of embodiments 8 or 9, wherein the AFC-ECM further comprises fibronectin and/or an isoform thereof.

Embodiment 11 is the cellular construct of any one of embodiments 5 to 10, wherein the AFC-ECM does not contain decorin, perlecan, and/or collagen (III).

Embodiment 12 is a method for making a cellular construct of mature cardiomyocytes on an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM), the method comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs), (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming the cellular construct; wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue.

Embodiment 13 is the method of embodiment 12, wherein the monolayer of mature cardiomyocytes is aligned on the AFC-ECM.

Embodiment 14 is the method of any one of embodiments 12 or 13, wherein fiber tracks are present on the cellular construct.

Embodiment 15 is a method for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro, the method comprising contacting the drug compound with the mature cardiomyocytes of any one of the cellular constructs of embodiments 5 to 11, and observing for a change in the electrophysiology of the mature cardiomyocytes to confirm whether the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

Embodiment 16 is the method of embodiment 15, wherein the change in the electrophysiology of the mature cardiomyocytes is prolongation of action potential duration (APD), and wherein prolongation of APD confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

Embodiment 17 is the method of embodiment 15, wherein the change in the electrophysiology of the mature cardiomyocytes is early after depolarization, and wherein early after depolarization (EAD) confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

Embodiment 18 is the method of embodiment 15, wherein the change in the electrophysiology of the mature cardiomyocytes is delayed after depolarization, and wherein delayed after depolarization (DAD) confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

Embodiment 19 is the method of embodiment 15, wherein the change in the electrophysiology of the mature cardiomyocytes is action potential duration (APD) plus rotors, and wherein prolongation of APD plus rotors confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

Embodiment 20 is the method of embodiment 15, wherein the change in the electrophysiology of the mature cardiomyocytes is an arrhythmia, and wherein the arrhythmia confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes.

The terms “about” or “approximately” are defined as being close to as understood by one of ordinary skill in the art, and in one non-limiting embodiment the terms are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%.

The term “substantially” and its variations are defined to include ranges within 10%, within 5%, within 1%, or within 0.5%.

As used herein, the terms “% w/w” or “wt. %” refers to a weight percentage of a component based on the total weight of material (e.g. a composition) that includes the component. In a non-limiting example, 10 grams of a component in 100 grams of a composition is 10% w/w of the component in the total weight of composition. As used herein, the terms “% v/v” or “vol. %” refers to a volume percentage of a component based on the total volume of material (e.g. a composition) that includes the component. In a non-limiting example, 10 mL of a component in 100 mL of a composition is 10% v/v of the component in the total volume of composition. As used herein, the term “% w/v” refers to a weight percentage of a component based on the total volume of material (e.g. a composition) that includes the component. In a non-limiting example, 10 grams of a component in 100 mL of a composition is 10% w/v of the component in the total volume of composition. As used herein, the term “% v/w” refers to a volume percentage of a component based on the total weight of material (e.g. a composition) that includes the component. In a non-limiting example, 10 mL of a component in 100 grams of a composition is 10% v/w of the component in the total weight of the composition.

The terms “inhibiting” or “reducing” or “preventing” or “avoiding” or any variation of these terms, when used in the claims and/or the specification includes any measurable decrease or complete inhibition to achieve a desired result.

The term “effective,” as that term is used in the specification and/or claims, means adequate to accomplish a desired, expected, or intended result.

The words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

The use of the word “a” or “an” when used in conjunction with the terms “comprising,” “having,” “including,” or “containing” (or any variations of these words) may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

The compositions and methods for their use can “comprise,” “consist essentially of,” or “consist of” any of the ingredients or steps disclosed throughout the specification. With respect to the transitional phrase “consisting essentially of,” in one non-limiting aspect, a basic and novel characteristic of the cellular constructs disclosed herein is their use in cardiotoxicity and/or proarrhythmic screening testing of drug compounds due to their ability to mature cardiomyocytes derived from stem cells to a maturation state resembling that of mature native adult cardiomyocytes and native heart tissue.

It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, compositions of the invention can be used to achieve methods of the invention.

Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: A photomicrograph of a Brightfield Image of the amniotic fluid cell-derived ECM at 100× power using a 10× objective lens.

FIG. 2: An atomic force photomicrograph of 3 representative 40×40 um sections of the amniotic fluid cell-derived ECM and a bone marrow cell-derived ECM showing topography, adhesion, and stiffness.

FIG. 3: Scatter plots showing quantification of adhesion and stiffness (elastic modulus) of bone marrow- and amniotic fluid- cell-derived ECMs. Each point represents an independent point of measurement.

FIG. 4: A photomicrograph showing Day 0 and Day 2 culture of iPSCs on amniotic fluid cell-derived ECM and a bone marrow cell-derived ECM.

FIG. 5: A plot of growth curves of iPSCs cultured in the presence of the amniotic fluid cell-derived ECM and a bone marrow cell-derived ECM.

FIG. 6: A photomicrograph of mature cardiomyocytes on an AFC-ECM in a single well—3.13 mm².

FIG. 7: A photomicrograph of mature cardiomyocytes on an AFC-ECM in a single well—2.15 mm².

FIG. 8: A photomicrograph of mature cardiomyocytes on an AFC-ECM in a single well—1.46 mm².

FIG. 9: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.54 mm².

FIG. 10: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.54 mm².

FIG. 11: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.54 mm².

FIG. 12: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.54 mm².

FIG. 13: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.13 mm².

FIG. 14: A photomicrograph of mature cardiomyocytes on AFC-ECM in a single well—0.04 mm².

FIG. 15: A photomicrograph of cardiomyocytes on standard Matrigel™ ECM in a single well—3.13 mm².

FIG. 16: A photomicrograph of cardiomyocytes on standard Matrigel™ ECM in a single well—2.15 mm².

FIG. 17: A photomicrograph of cardiomyocytes on standard Matrigel™ ECM in a single well—1.46 mm².

FIG. 18: A photomicrograph of cardiomyocytes on standard Matrigel™ ECM in a single well—0.54 mm².

FIG. 19: A photomicrograph of cardiomyocytes on standard Matrigel™ ECM in a single well—0.13 mm².

FIG. 20: A photomicrograph of mature cardiomyocytes on a BM-ECM in a single well—2.15 mm².

FIG. 21: A photomicrograph of mature cardiomyocytes on a BM-ECM in a single well—1.46 mm².

FIG. 22: A schematic of the configuration of instruments to record action potential or calcium transient measurements using mature cardiomyocytes on AFC-ECM in multi-well plates.

FIG. 23: Recordings of spontaneous action potentials recorded from cardiomyocytes cultured on Matrigel™ ECM, BM-ECM, and AFC-ECM, baseline and after drug E4031.

FIG. 24: Bar graph of number of Stable Rotors (TdP like arrhythmia) from cardiomyocytes cultured on Matrigel™ ECM, BM-ECM, and AFC-ECM after contact with drug E4031.

FIG. 25: Recordings of spontaneous action potentials recorded from mature cardiomyocytes cultured on AFC-ECM for various drugs.

FIG. 26: Bar graph of total arrythmias recorded for all doses of each of the listed drugs.

FIG. 27: Bar graph of % of well with arrythmia @10× the effective therapeutic plasma concentration (ETPC) of each of the listed drugs.

FIG. 28: Bar graph of the action potential triangulation (APD90-APD30) in time (ms) of each of the listed drugs.

FIG. 29: Bar graph of the action potential triangulation (APD90-APD30) in time (ms) of each of some of the listed drugs comparing cardiomyocyte performance of cardiomyocytes on the AFC-ECM (SBS-AF Matrix) versus on Matrigel™ ECM.

FIG. 30: Bar graph of the maximum drug-induced action potential triangulation of the listed drugs comparing cardiomyocyte performance of iCell® hiPSC-CMs from Cellular Dynamics (blank circles) versus Cor.4U® hiPSC-CMs from Ncardia (dark circles) at any concentration of the listed drugs. Figure from Blinova et al, 2018, Cell Reports.

FIG. 31: Photomicrophraphs of hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for Troponin I, using DAPI to mark the nuclei.

FIG. 32: Photomicrophraphs of hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for α-actinin using DAPI to mark the nuclei.

FIG. 33: Photmicrographs of hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for cTnT and N Cadherin, using DAPI to mark the nuclei.

FIG. 34: Photomicrographs of a single hiPSC-CM cell cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for cTnT using DAPI to mark the nuclei.

FIG. 35: Photomicrographs of a single hiPSC-CM cell cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for α-actinin using DAPI to mark the nuclei.

FIG. 36: Graph of a comparison of the cellular circularity of the single cells shown in FIG. 35.

FIG. 37: Photomicrographs of hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescentstaining for cTnI expression, using DAPI to mark the nuclei.

FIG. 38: Western blotting of hiPSC-CMs on Matrigel™ ECM and AFC-ECM for cTnI expression and GAPDH.

FIG. 39: Graph of cTnI Expression relative to GAPDH of hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM.

FIG. 40: Photomicrographs of hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM stained for mitochondria with MitoTracker Red.

FIG. 41: Graph showing the MitoTraker™ Red fluorescence intensity/cardiomyocyte for hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM.

FIG. 42: Photomicrographs (transmitted light) of hiPSC-CMs cultured on Matrigel™ ECM and AFC-ECM that were coated on microelectrode array (MEA) plates.

DETAILED DESCRIPTION

Human stem cell derived cardiomyocytes, such as those derived from human induced pluripotent stem cells (hiPSC-CMs), that have been matured in culture on an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM) have demonstrated better, more consistent cardiotoxicity and proarrhythmia assay results than immature hiPSC-CMs or hiPSC-CMs matured on other ECMs, such as Matrigel™ ECM and bone marrow cell-derived ECM. The hiPSC-CMs matured on an AFC-ECM surprisingly have demonstrated a higher state of maturation than hiPSC-CMs matured on other ECMs, such as Matrigel™ ECM and even on other natural cell derived ECMs such as bone marrow cell-derived ECM, as shown by their cellular morphology and sarcomere structure that are found in cardiomyocytes of normal adult human cardiac tissue. Furthermore, a more robust expression of cTnI (cardiac troponin I) protein, as demonstrated by western blotting techniques, has been seen for hiPSC-CMs cultured on AFC-ECM than for hiPSC-CMs cultured on Matrigel™ ECM. Also, hiPSC-CMs cultured on AFC-ECM have more mitochondria and mitochondria with more polarized inner membrane potential than hiPSC-CMs cultured on Matrigel™ ECM. Thus, the AFC-EMC can stimulate mitochondrial biogenesis, maturation, and function in the hiPSC-CMs. Normal adult or mature human cardiac human tissue is characterized by rod shaped cells with sarcomere structure (striped appearance). The morphology and sarcomere structures of the cardiomyocytes can be identified visually by microscopy (transmitted light or by immunofluorescent staining). As a non-limiting example, the morphology and sarcomere structure of the cardiomyocytes matured on AFC-ECM can be distinctly seen by the presence of rod shaped cells with a striped appearance identified by arrows in the photomicrograph of FIG. 14. Additionally, the use of a silicone substrate such as PDMS were not needed to achieve these results. Surprisingly, a cellular construct comprising an AFC-ECM and a monolayer of mature cardiomyocytes that have been matured from immature hiPSC-CMs in culture on the AFC-ECM has shown to be useful, for example, by allowing consistent visualization of drug induced arrhythmias such as Torsades de Pointes (TdP) in high throughput in vitro screening assays. This “TdP in a dish” technology is a major advance over the reliance on field potential duration (MEA technology) or action potential duration prolongation as surrogate markers for drug induced TdP. Thus, the cellular construct and methods disclosed herein go beyond the current CiPA Initiative's guidelines by developing a more comprehensive and predictive in vitro arrhythmia assay that allows for visualization of arrhythmic events in an in vitro model, rather than simple polarization and depolarization events that are indirect indicators of proarrhythmia. The cellular system and methods outlined in this disclosure allow for arrhythmic events to be propagated and visualized in an in vitro human cardiac monolayer model system. In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be characterized by having rod shaped cells with distinct sarcomere structure (striped appearance). In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

Disclosed herein are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture forming mature cardiomyocytes (mature hiPSC-CMs). Also disclosed herein is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and/or proarrhythmic screening assays of drug compounds. Also disclosed herein are methods for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro using such cell constructs.

A. Amniotic Fluid Cell-Derived Extracellular Matrix (AFC-ECM)

Perinatal cells can be divided into three groups: cells from amniotic fluid; cells from the placenta; and cells from the umbilical cord. Amniotic fluid has several sources of cells including cells derived from the developing fetus sloughed from the fetal amnion membrane, skin, and alimentary, respiratory, and urogenital tracts. Placenta also has several sources of cells including the membrane sheets (amnion and chorion), the villi, and the blood. Umbilical cord cells generally come from two sources, cord blood and Wharton's jelly. The cells from these three perinatal sources can include stem cells. The cells used to produce the amniotic fluid cell-derived ECM of the invention are obtained from the amniotic fluid of a mammal including but not limited to a human (Homo sapiens), murine, rabbit, cat, dog, pig, equine, or primate. In preferred embodiments, the cells are from the amniotic fluid of a human. The amniotic fluid can be sourced from humans at full-term births (greater than about 37 weeks gestational age) or pre-term births (less than about 37 weeks gestational age). Pre-term births include late pre-term births (about 33 to about 37 weeks gestational age) moderate pre-term births (about 29 to about 33 weeks gestational age), and extreme pre-term births (about 23 to about 29 weeks gestational age). The amniotic fluid can be sourced from humans prior to birth at any gestational age where amniotic fluid is present, and can be combined with sources of amniotic fluid from births. Generally, prior to birth, amniotic fluid is collected by an amniocentesis procedure. In some embodiments the amniotic fluid is sourced from humans at full-term births, at pre-term births, at late pre-term births, at moderate pre-term births, at extreme pre-term births, or prior to birth, or combinations thereof. In some embodiments, the amniotic fluid is sourced prior to birth and is collected from about 10 weeks gestational age up to birth, or from about 10 weeks to about 23 weeks gestational age, or from about 10 weeks to about 16 weeks gestational age, or from about 12 weeks gestational age up to birth, or from about 12 weeks to about 23 weeks gestational age, or from about 12 weeks to about 16 weeks gestational age. In some embodiments, the amniotic fluid sourced prior to birth is collected by an amniocentesis procedure. The cells can be obtained and isolated from amniotic fluid by techniques known in the art, such as those disclosed in Murphy et. al., Amniotic Fluid Stem Cells, Perinatal Stem Cells, Second Ed. 2013.

Amniotic fluid is comprised of cells having the ability to differentiate into cell types derived from all 3 embryonic germ layers (ectoderm, endoderm, mesoderm) spontaneously or as a result of treatment with specific growth factors or combinations of growth factors known to one of skill in the art. That is, a single cell has the capacity to be induced to express genes which are specific to any of the three germ layers. Amniotic fluid also contains a mixture of different cell types including cells derived from the developing fetus sloughed from the fetal amnion membrane, skin, and alimentary, respiratory, and urogenital tracts. Because of the origin of the amniotic fluid and placental membranes, these cells can maintain highly multipotent differentiation potential and comprise a cell population that contains cells of all three germ layers. The amniotic fluid cells can comprise stem cells. In some embodiments, the amniotic fluid cells are isolated stem cells. In some embodiments, the amniotic fluid cells comprise stem cells having the ability to differentiate into cell types derived from all 3 embryonic germ layers (ectoderm, endoderm, mesoderm) and/or multipotent stem cells, and/or pluripotent stem cells.

The amniotic fluid cell-derived ECM disclosed herein can comprise various proteins. The proteins of the ECM can be identified by techniques known in the art and include mass spectroscopy and immunohistochemical staining. The ECM can include, but is not limited to the components listed in Table 2 (see Example 1 below) and any variants, derivatives, or isoforms thereof. The amniotic fluid-cell derived ECM can include any combination of any of the components and any variants, derivatives, or isoforms thereof from Table 2. In some embodiments, a combination can comprise, consist essentially of, or consist of: laminin, collagen alpha-1 (XVIII), basement membrane-specific heparan sulfate proteoglycan core protein, agrin, vimentin, and collagen alpha-2 (IV), and/or isoforms thereof. In some embodiments, the isoform of collagen alpha-1 (XVIII) is isoform 2. In some embodiments, the isoform of agrin is isoform 6. In some embodiments, the cell-derived ECM further comprises, consist essentially of, or consists of fibronectin and/or an isoform thereof. In some embodiments, the amniotic fluid cell-derived ECM does not contain any one of or all of decorin, perlecan, and collagen (III). Some noteworthy differences in proteins between the amniotic fluid cell-derived ECM of the present inventions and a bone marrow cell-derived matrix are described in Table 1.

TABLE 1

Differences Between the Amniotic Fluid Cell-Derived ECM (AFC-

Matrix) and a Bone Marrow Cell-Derived Matrix (BM-Matrix)

Protein/
Difference between AFC-

Gene Code
Matrix & BM-Matrix
Physiologic Relevance

Laminin
5 sub-units are abundant in
Laminin is known to

AFC Matrix; Low expression
support adhesion and

in BM-Matrix
expansion of pluripotent

cells.

Collagen
Abundant in AFC Matrix;
Important for ocular

XVIII
Absent in BM-Matrix
development

Agrin
Present in AFC Matrix;
produced by motoneurons

Absent in BM-Matrix
to induce aggregation of

acetylcholine receptors

Biglycan
Abundant in BM-Matrix;
Regulates bone and muscle

Low expression in AFC
development

Matrix

Collagen I
Overexpressed in BM-Matrix
Key to fibrillar proteins;

relative to AFC Matrix
highly abundant in bone

Periostin
Present in BM-Matrix;
Regulates mineralization;

Absent in AFC Matrix
Marker of

noncardiomyocyte lineage

cells in heart

The amniotic fluid cell-derived ECM can be produced by the following process: (a) isolating cells from amniotic fluid, (b) seeding the isolated cells onto a cell culture container or onto a cell culture container coated with a substrate, (c) adding a culture media to the cell culture container, and (d) culturing the cells, thereby producing a cell-derived ECM, and (e) optionally decellularizing the cell-derived ECM.

Any cell seeding density may be used which allows cells to form a confluent monolayer immediately or after a period of time in culture. In some embodiments, the seeding density is about 10 cells/cm²-about 100,000 cells/cm², or about 100 cells/cm²-about 75,000 cells/cm², or about 500 cells/cm²-about 50,000 cells/cm², or about 500 cells/cm²-about 10,000 cells/cm², or about 500 cells/cm²-about 5,000 cells/cm², or about 500 cells/cm²-about 2,500 cells/cm², or about 1,000 cells/cm²-about 25,000 cells/cm², or about 2,000 cells/cm²-about 10,000 cells/cm², or about 3,000 cells/cm²-about 5000 cells/cm².

Any type of container suitable for cultivation of cells can be used for the present invention. Examples include, but are not limited to cell culture flasks, T-flasks, stirred flasks, spinner flasks, fermenters, and bioreactors. Rocking bottles, shaking flasks, tubes, and other containers are also suitable containers when placed on a rocking platform or shaker. The cell culture container can be coated with a substrate to allow for better cell adhesion. A non-limiting example of a suitable substrate for coating the cell container is fibronectin.

Various commercially available cell culture media, e.g., alpha Minimum Essential Media (α-MEM) culture media (Thermo Fisher Scientific, Grand Island, N.Y.), are suitable for culturing amniotic fluid cells. The commercially available culture media can be modified by adding various supplemental substances to the media, e.g. sodium bicarbonate, L-glutamine, penicillin, streptomycin, Amphotericin B and/or serum. The serum can be fetal bovine serum. The media can also be serum free. Additionally, substances such as L-ascorbic acid can be added to the media or modified media to induce cell production of an ECM.

The initial culture media can be changed and/or replaced with another media at various times during the culturing process. For example, the initial media can be a “Complete Media” and then be replaced by an “Inducing Media” during the culturing process. A non-limiting example of a “Complete Media” contains (α-MEM) plus 2 mM L-Glutamine plus antibiotic-antimycotic plus 15% Fetal Bovine Serum. A non-limiting example of an “Inducing Media” contains the “Complete Media” plus 50 mM L-Ascorbic Acid.

The culturing of the amniotic fluid cells can take place in an incubator at 37° C., 5% CO₂, and 90% humidity. Culturing can take place under various environmental conditions including, but not limited to normoxic, i.e., 20-21% oxygen in the atmosphere, or hypoxic conditions.

Decellularizing the amniotic fluid cell-derived ECM of the amniotic fluid cells can include removing the viable amniotic fluid cells or rendering the amniotic fluid cells non-viable. The amniotic fluid cells can be decellularized from the ECM by using methods known in the art and can include, but are not limited to lysing the amniotic fluid cells and then removing the lysed amniotic fluid cells by washing. Various substances can be used to remove the amniotic fluid cells from the ECM. Non-limiting examples include an “Extraction Buffer” containing TRITON X-100 and ammonium hydroxide in PBS buffer. After the ECM has been decellularized of amniotic fluid cells, the resulting ECM is thereby essentially cell-free or free of viable amniotic fluid cells. If feeder cells are used, then the decellularizing methods also apply to any viable feeder cells present on the ECM, thereby resulting in the ECM being essentially free or free of viable feeder cells. The decellularizing methods also apply to any viable cells present on the ECM, thereby resulting in the ECM being essentially free or free of any viable cells. Thus, a decellularized ECM means that the ECM is acellular, meaning that the ECM is free of any viable cells.

In some embodiments, the amniotic fluid cell-derived ECM (AFC-ECM) is a three-dimensional (3D) ECM.

The methods described supra also apply to producing cell-derived ECMs from other perinatal cells such as cells from the umbilical cord including the cord blood and Wharton's jelly; and cells from placenta tissue including the membrane sheets (amnion and chorion), the villi and the blood.

In one embodiment, a perinatal cell-derived ECM is produced by the following process: (a) isolating cells from an umbilical cord, (b) seeding the isolated cells onto a cell culture container or onto a cell culture container coated with a substrate, (c) adding a culture media to the cell culture container, and (d) culturing the cells, thereby producing a cell-derived ECM, and (e) optionally decellularizing the cell-derived ECM. In some embodiments, the cells isolated from the umbilical cord are from the cord blood and/or the Wharton's jelly.

In another embodiment, a perinatal cell-derived ECM is produced by the following process: (a) isolating cells from placenta tissue, (b) seeding the isolated cells onto a cell culture container or onto a cell culture container coated with a substrate, (c) adding a culture media to the cell culture container, and (d) culturing the cells, thereby producing a cell-derived ECM, and (e) optionally decellularizing the cell-derived ECM. In some embodiments, the cells isolated from the placenta tissue are from the membrane sheets (amnion and/or chorion), the villi, and/or the blood.

In one aspect, disclosed is a cell-derived extracellular matrix (ECM) derived in vitro from cells isolated from an umbilical cord. In some embodiments, the cells isolated from the umbilical cord are from the cord blood and/or the Wharton's jelly.

In another aspect, disclosed is a cell-derived extracellular matrix (ECM) derived in vitro from cells isolated from placenta tissue. In some embodiments, the cells isolated from the placenta tissue are from the membrane sheets (amnion and/or chorion), the villi, and/or the blood.

B. Cellular Constructs and Methods for the Maturation of Immature hiPSC-CMs

Disclosed herein is a method for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells, the method comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) contacting the immature hiPSC-CMs with the AFC-ECM; and (d) culturing the immature hiPSC-CMs with the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs, thereby forming mature cardiomyocytes (mature hiPSC-CMs); wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. Normal adult human cardiac human tissue is characterized by rod shaped cells with sarcomere structure (striped appearance). The morphology and sarcomere structures of the cardiomyocytes can be identified visually by microscopy. As a non-limiting example, the morphology and sarcomere structure of the cardiomyocytes matured on AFC-ECM can be distinctly seen by the presence of rod shaped cells with a striped appearance identified by arrows in the photomicrograph of FIG. 14.

Also disclosed herein is a cellular construct comprising a monolayer of mature cardiomyocytes on an extracellular matrix derived from cells isolated in vitro from amniotic fluid (AFC-ECM), wherein the mature cardiomyocytes are AFC-ECM cultured cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), and wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In certain aspects, the mature cardiomyocytes can be matured from immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture on the AFC-ECM, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some aspects, the mature cardiomyocytes include the inward-rectifier Kir2.1 potassium channel and/or express inward-rectifier potassium channel Kir2.1. In some embodiments, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In some embodiments, fiber tracks are present on the construct. In some embodiments, the AFC-ECM comprises laminin, collagen alpha-1 (XVIII), basement membrane-specific heparan sulfate proteoglycan core protein, agrin, vimentin, and collagen alpha-2 (IV), and/or isoforms thereof. In some embodiments, the isoform of collagen alpha-1 (XVIII) is isoform 2, and/or wherein the isoform of agrin is isoform 6. In some embodiments, the AFC-ECM further comprises fibronectin and/or an isoform thereof. In some embodiments, the AFC-ECM does not contain decorin, perlecan, and/or collagen (III). In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated).

Also disclosed herein is a method for the preparation of a cellular construct comprising mature cardiomyocytes on an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM), the method comprising (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs), (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; and (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming the cellular construct, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In some embodiments, fiber tracks are present on the construct.

Immature hiPSC-CMs can be obtained from commercial sources such as Cellular Dynamics International-FUJI under the trade name iCell®, and Takara Bio under the trade name Cellartis®. iCell® Cardiomyocytes, iCell® Cardiomyocytes², and Cellartis® Cardiomyocytes are cryopreserved viable cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) available in vials. Immature hiPSC-CMs can also be generated from patient specific hiPSCs in a laboratory setting for a specific individual. In this case, differentiation of the hiPSCs can be accomplished using the small molecule protocol to obtain beating cardiomyocytes by day 8-10 using GSK3 inhibitor, RPMI/B27 minus insulin, Wnt Inhibitor and RPMI/B27 plus insulin at various days during the 7-day differentiation period. Suitable non-limiting examples of methods to generate immature hiPSC-CMs are disclosed in US publication 2015/0329825 herein incorporated by reference. In some embodiments, the immature hiPSC-CMs do not express inward-rectifier potassium channel Kir2.1. In some embodiments, the immature hiPSC-CMs do not include rod shaped cells with distinct sarcomere structure. In some embodiments, the immature hiPSC-CMs can be characterized by having less mitochondria than mature cardiomyocytes, by having disorganized myofilaments, by having a circular shape, and/or by having a single nucleus.

The AFC-ECM can be obtained using the production methods disclosed herein in this disclosure and can have the characteristics as described in this disclosure. In some embodiments, the AFC-ECM is decellularized prior to contact with the immature hiPSC-CMs.

The immature hiPSC-CMs can be in suspension when in contact with the AFC-ECM or the cells can be plated directly on the AFC-ECM which is in or on suitable cell culture containers or in multi-well plates. Non-limiting examples of suitable multi-well plates include 6-, 12-, 24-, 48, 96- and 384-well plates. In some embodiments, the contact surfaces of the cell culture containers or multi-well plates are coated with polydimethylsiloxane (PDMS) prior to the formation of the AFC-ECM. In some embodiments, the contact surfaces of the cell culture containers or multi-well plates are not coated with PDMS prior to the formation of the AFC-ECM. Any cell seeding density of immature hiPSC-CMs can be used. In some embodiments, a cell seeding density of immature hiPSC-CMs which allows the cells to form a confluent monolayer immediately or after a period of time in culture is used. Cell density can be modified as desired to improve monolayer formation. In multi-well plates, the immature hiPSC-CM cells are placed in the center of each well. Non-limiting examples of cell seeding densities of immature hiPSC-CMs in various multi-well plates are as follows: in 6-well plates, about 200,000 cells can be plated per well; in 12-well plates, about 150,000 cells can be plated per well; in 24-well plates about 175,000 cells can be plated per well; in 48-well plates about 100,000 cells can be plated per well; in 96-well plates, about 50,000 cells can be plated per well; in 384-well plates, about 15,000 cells can be plated per well. In some embodiments, the cell seeding density of immature hiPSC-CMs is about 50,000 cells per well in a 96-well plate. In some embodiments, the cell seeding density is about 200,000 cells per well in a 6-well plate. To induce maturation of the immature hiPSC-CMs, a suitable culture media such as RPMI media or Media 199 media is added to the immature hiPSC-CMs in contact with the AFC-ECM, and the cells are cultured with the AFC-ECM using standard cell culture techniques for a period of time, generally 7 days, until the cells have matured into mature cardiomyocytes having similar morphology as native adult cardiomyocytes. During the first 3 to 4 days, the immature hiPCS-CMs are adhering, forming a continuous monolayer, and beginning the maturation process. Surprisingly, the period of time for maturation of the cardiomyocytes can take 7 days or less, whereas generally a much longer period of time is typical with other substrates, e.g., up to 100 days. The morphology of these mature cardiomyocytes can be characterized by rod shaped cells with distinct sarcomere structure (striped appearance), the fundamental contractile unit of muscle, that can be visualized using conventional light microscopy techniques. In some embodiments, the mature cardiomyocytes can be further characterized by having greater amounts of mitochondria than immature hiPSC-CMs, by having organized, compact myofilaments, and/or by having two nuclei (bi-nucleated). Also, the AFC-ECM can naturally produce fiber tracks that the mature cardiomyocytes follow. This produces a degree of anisotropy to the monolayer that more closely mimics the native heart. Thus, the cardiomyocytes can be naturally aligned on the AFC-ECM following the alignment of the AFC-ECM that has been laid down in a natural anisotropic configuration by the amniotic fluid cells during formation of the AFC-ECM. In various embodiments, the period of time for the immature hiPSC-CMs to mature in culture can be 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, or 120 days. Preferably, the period of time for the maturation of the cardiomyocytes is 14 days, or more preferably, 10 days, or even more preferably 7 days. In some embodiments the period of time for the immature hiPSC-CMs to mature in culture is 7 days. In some embodiments, the immature hiPSC-CMs are plated on the AFC-ECM. In some embodiments, the mature cardiomyocytes form as a confluent monolayer on the AFC-ECM during culture, thereby forming a cellular construct comprising a monolayer of mature cardiomyocytes on the AFC-ECM. In some embodiments, the mature cardiomyocytes are aligned on the AFC-ECM. In some embodiments, the immature hiPSC-CMs are plated on the AFC-ECM in multi-well plates. In some embodiments, the multi-well plates have inserts of polydimethylsiloxane (PDMS). In some embodiment, the multi-well plates do not have inserts of PDMS.

C. Methods for Determining the Cardiotoxicity and/or Proarrhythmic Effect of a Drug Compound

Disclosed herein is a method for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro, the method comprising contacting the drug compound with the mature cardiomyocytes of any one of the cellular constructs disclosed throughout the specification, and observing for one or more changes in the electrophysiology of the mature cardiomyocytes to confirm whether the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes. One or more changes in the electrophysiology of the mature cardiomyocytes indicates and confirms that the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes. The one or more changes of the electrophysiology of the mature cardiomyocytes can include, but are not limited to, APD prolongation, APD prolongation plus rotors, and/or various types of arrhythmias, such as tachyarrhythmia (TA), quiescence (Q), delayed afterdepolarization (DAD), and/or early afterdepolarization (EAD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is prolongation of action potential duration (APD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is early after depolarization (EAD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is delayed after depolarization (DAD). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is action potential duration (APD) plus rotors. In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is an arrhythmia. In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is tachyarrhythmia (TA). In some embodiments, the change in the electrophysiology of the mature cardiomyocytes is quiescence (Q). Observations can also include the cell viability, cell density, and/or morphology of the cells. In some aspects, the cellular construct can be prepared by a process comprising: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; and (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming a cellular construct, wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In other aspects, the method can comprise contacting the drug compound with any one of the cellular constructs disclosed throughout the specification and observing for cardiotoxic and/or proarrhythmic events. In one particular instance, the method comprises: (a) providing immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs); (b) providing an extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM); (c) plating the immature hiPSC-CMs on the AFC-ECM; (d) culturing the plated immature hiPSC-CMs on the AFC-ECM in a culture media to induce maturation of the immature hiPSC-CMs into mature cardiomyocytes and to form a monolayer of the mature cardiomyocytes on the AFC-ECM, thereby forming a cellular construct; (e) contacting the drug compound with the monolayer of the mature cardiomyocytes of the construct; and (f) observing for a change in the electrophysiology of the mature cardiomyocytes to confirm whether the drug compound has a cardiotoxic and/or proarrhythmic effect on the mature cardiomyocytes; wherein the mature cardiomyocytes are characterized by rod shaped cells with distinct sarcomere structure resembling adult human cardiac tissue. In some embodiments, the immature hiPSC-CMs are plated on the AFC-ECM in a multi-well plate. In some embodiments, the multi-well plates have inserts of polydimethylsiloxane (PDMS). In some embodiment, the multi-well plates do not have inserts of PDMS. In some embodiments, the immature hiPSC-CMs do not express inward-rectifier potassium channel Kir2.1. In some embodiments, the monolayer of mature cardiomyocytes is aligned on the AFC-ECM. In some embodiments, fiber tracks are present on the cellular construct.

The cardiotoxicity and/or proarrhythmia testing can be conducted using any type of equipment suitable for measuring such activity. In some embodiments, the cellular constructs of monolayers of mature cardiomyocytes on AFC-ECM are prepared as described supra. After the maturation process (generally 7 days or less), the electrophysiology of each well is observed using a plate reader. A suitable voltage sensitive or calcium sensitive fluorescent dye is loaded into each well. Non-limiting voltage sensitive dyes include FluoVolt™ dye commercially available from ThermoFisher. In some embodiments, the plate reader can rely on a suitable high spatiotemporal CCD camera combined with suitable lighting, such as light emitting diodes (LEDs), of the appropriate wavelength to excite each dye. Such high spatiotemporal CCD cameras are commercially available from SciMeasure. In some embodiments, the camera image acquisition rate is greater than or equal to 150 frames per second. In some embodiments, the camera and lens combination are designed such that it allows visualization of all the wells of the multi-well plate simultaneously with sufficient resolution to observe action potential and calcium wave propagation. Each plate is centered under the camera system, lighting is switched on and camera acquisition is initiated and electrophysiological activity is recorded. Experiments are performed at about 37° C. After baseline readings are made, the drug to be tested is added to the wells and the effects are recorded. Spontaneous activity is recorded for a sufficient period of time to obtain images, e.g. at least 10 seconds. The images can be stored on a computer. Images are analyzed and action potential duration, conduction velocity, beat rate and activation patterns can be quantified using image analysis software. Visualization of electrical wave patterns is important to determine a drug compound's effect to cause potentially fatal arrhythmias, e.g., Torsades de Pointes (TdP). Thus, in addition to providing information on a compound's effect on spontaneous action potential duration, the methods disclosed herein can also provide information on impulse conduction velocity and activation pattern depending on the type of equipment used.

D. Methods to Expand/Proliferate Mammalian Stem Cells

Also disclosed herein are methods of using a cell-derived extracellular matrix derived in vitro from cells isolated from amniotic fluid (AFC-ECM) for the isolation, maintenance, and expansion/proliferation of mammalian cells. In vitro cell culture is perhaps the most ubiquitous, important, and poorly understood aspect of all cell biology as well as the developing fields of regenerative medicine and tissue engineering. Firstly, it allows for the observation of cell behavior so that various aspects of cell function may be studied in detail. Secondly, it allows for increase in numbers of specific cell groups. For basic research, as well as many clinical applications, it is necessary to achieve large quantities of relatively rare cells from small biological samples. In-vitro cell culture permits small numbers of cells to be expanded outside the body to achieve more relevant numbers. Lastly, it permits the storage of cells for later use. By expanding cell numbers in-vitro, and freezing viable cells for later use, relatively small biological samples can yield cells for multiple experiments over the span of days, months, or even years.

Despite the omnipresence of cell culture, the effects that in vitro culture has on the native characteristics of the cells is still relatively poorly understood. Many of the current practices have arisen not from deliberate thought, planning, and experimentation, but instead from chance observations. Mammalian cell culture began in the early 1900s when, in 1911, Alexis Carrel and Montrose Burrows first published an academic paper on the cultivation of mammalian tissues in vitro. They were studying the physiology and anatomy of tissues by cutting sections of mammalian tissues and placing them on microscope slides. They then noticed that some cells migrated out of the tissue onto the slide. They went on to describe techniques for culturing cells in perpetuity. It now appears that some of their observations may not have been valid, but their work paved the way for modern cell culture.

After the discovery of hematopoietic stem cells (HSCs), groups all over the world were studying (HSCs). During their culture (in suspension), it was observed that a sub-population of bone marrow cells stuck to the bottom of the plastic flasks and began to proliferate. These cells were later recognized to be distinct from HSCs, and were eventually dubbed mesenchymal stem cells (MSCs). Because of this chance observation that lead to the discovery of MSCs, plastic adherence is still widely used as a defining attribute of MSCs and many other mammalian cell types.

The practice of culturing cells on plastic substrates can be problematic because there is substantial evidence, that is now widely accepted in the literature, demonstrating the critical role of the microenvironment in regulating cell function. The microenvironment has been shown to help direct the differentiation of stem and progenitor cells, and regulate the behavior of mature cell types.

When cells are removed from their native environment to be expanded in-vitro they can lose important cues from their surrounding extracellular matrix or microenvironment which relay important information to the cells regarding the composition and state of their surroundings. Changes to a cell's microenvironment can have a profound effect on the behavior of those cells. The current standard for isolation and expansion of most adherent cells in vitro is to place the cells in culture vessels composed of polystyrene (plastic). The polystyrene may have been treated in some manner to facilitate cell attachment and growth but the surface is, in most cases, completely foreign to the cell. In other cases, the surface may be coated with individual matrix proteins (e.g. fibronectin or collagen) or some combination of proteins. These simple substrates disregard the complexity of the native microenvironment as well as the critical role of the microenvironment in normal cell function. The cell will immediately begin to respond to this foreign environment in a manner that is much different than when the cell is in its native environment.

Five major approaches are currently employed to address this issue of culturing cells on plastic substrates:

1. Ignore the problem.—Instead of trying to achieve a desired function that matches what would be expected in vivo, a multitude of cell types can be tested in various media in order to find cells that will exhibit a specific desired function without the appropriate matrix substrate. This approach is unsophisticated and often fails to produce desired results because of the complex interplay of variables and the breadth of interactions between cells and the extracellular matrix.

2. Identify key components.—Many academic laboratories and several companies have taken the approach of considering the tissue from which cells are isolated and looking for unique elements of that tissue that may be important for cell function. Cells are then cultured on simple substrates consisting of only one or a few matrix components. This approach often fails because matrices are naturally very complex environments including over one-hundred different proteins in some cases. Cells respond just as strongly to signals they need and fail to receive, as to signals they do not need and do receive.

3. Shotgun approach—The use of protein gels like MATRIGEL™ employs a sort of shotgun approach. A gel is created that contains many different matrix proteins with the hopes that it will contain the necessary binding motifs for many different cell types. This approach may fail by providing cues that push cells in a particular direction or by failing to provide all the cues that cells are expecting.

4. Tissue-derived matrices—This is a biomimetic approach that typically involves isolating a tissue of interest from a genetically similar animal, physically disrupting or chemically digesting the tissue to obtain a solution or uniform suspension, and then coating culture vessels with the deconstructed tissue. For example, someone who wishes to culture satellite cells, might collect muscle, homogenize the tissue, and then coat a culture vessel in homogenized muscle prior to seeding the cells. This method often fails for a few reasons. Firstly, even within a specific tissue type, the stem cell/progenitor cell niche, may be distinct from the rest of the tissue. Simply homogenizing muscle does not guarantee that an appropriate niche is being created. Secondly, the niche consists of structural and physical cues, in addition to biochemical cues. Even if many/most of the biochemical cues are present in a tissue homogenate, the structure has been destroyed, and cells may sense very different mechanical cues. Lastly, manufacturability of tissue derived matrices is dependent on availability of tissues. This affects the total amount of cell culture possible and contributes to lot-to-lot variability.

5. Cell-derived matrices—Cells in culture can be induced to secrete a matrix in their culture vessel. This matrix is the best approximation available of the in vivo niche, and can be manufactured in vitro. Cells can be induced in vitro to elaborate a matrix and then the cells can subsequently be eliminated from the matrix, for example by using non-ionizing detergent to retain structure and chemistry of the matrix. This approach has several key advantages. (1) The matrix structure can be recreated and left undisturbed. (2) The matrix can be customized based on tissue/cell type of interest. (3) The matrix can be specific to stem and progenitor cell niche. (4) The matrix can be manufactured in large quantities.

With respect to cell-derived matrices, not all cell types can be efficiently isolated and expanded on any given cell-derived matrix. In fact, pluripotent stem cells (PSCs) appear to have much different requirements for a supportive growth substrate than do other types of cells. It is known that the specific cell type used to produce a matrix will have an effect on the composition of the matrix, and therefore, the reaction of various cell types to that matrix (see Marinkovic, M. et al., One size does not fit all: developing a cell-specific niche for in vitro study of cell behavior. Matrix Biol. 54-55, 426-441 (2016)). Prior work disclosed in U.S. Pat. No. 8,084,023 has described the production and composition of an extracellular matrix produced by bone marrow stromal or mesenchymal stem cells (see also Chen, X. et al., Extracellular Matrix Made by Bone Marrow Cells Facilitates Expansion of Marrow-Derived Mesenchymal Progenitor Cells and Prevents Their Differentiation into Osteoblasts. Journal of Bone and Mineral Research 22, 1943-1956 (2007) and Lai, Y. et al., Reconstitution of marrow-derived extracellular matrix ex vivo: a robust culture system for expanding large-scale highly functional human mesenchymal stem cells. Stem cells and development 19, 1095-107 (2010)). This bone marrow cell derived matrix has been shown to support the expansion of other MSCs but has not been effective for the attachment and growth of other types of stem cells, specifically, induced pluripotent stem cells (iPSCs). iPSCs have exhibited an expanded potential to form cells and tissues from a much broader category than MSCs. This represents a particularly interesting challenge, because the difficulty of growing a confluent monolayer of iPSCs in standard culture conditions makes it impractical to produce a cell-derived matrix from iPSCs. A major limitation of previous cell-derived matrices, is that in order to make a tissue-specific matrix (e.g., bone marrow matrix from bone marrow MSCs, adipose matrix from adipose MSCs, or endothelial matrix from hUVECs), it is necessary that the target population of cells already be capable of adhering to the starting substrate. A difficulty with iPSCs, embryonic stem cells (ES), and many other cell types is that they do not readily adhere to simple substrates.

The present disclosure provides a solution to at least some of the aforementioned limitations and deficiencies in the art relating to cell-derived extracellular matrices (ECMs) to support the isolation, expansion and proliferation of pluripotent stem cells (PSCs), including but not limited to induced pluripotent stem cells (iPSCs) and embryonic stem cells (ES). The solution is premised on the use of an amniotic fluid cell-derived extracellular matrix. The use of uncommitted, readily adherent, and highly proliferative perinatal cells found in amniotic fluid allows for the creation of an extracellular matrix (ECM) that surprisingly, supports adhesion, isolation, expansion, and proliferation of these PSCs. This technical achievement was not possible with the cell-derived ECMs of the prior art.

The function of mammalian cells is determined, largely, by the environment, e.g., an extracellular matrix, in which they reside. They react to signals that are present in their environment (positive signals) and also to signals that are required but are not present (negative signals). It is likely that uncommitted stem cells can produce a matrix that contains niche motifs necessary to maintain stem cell viability and stemness, but lack many lineage specific signals that more mature cells may secrete which would push a stem cell toward a particular fate. Without being bound by theory, it is suggested that a less mature cell, e.g., a perinatal cell or perinatal stem cell, may produce an ECM that is different from ECMs disclosed previously in the art, such as bone marrow stromal cell-derived ECMs, and may allow for better isolation and expansion/proliferation of stem cells with higher potential than mesenchymal stem cells (MSCs), such as pluripotent stem cells (PSCs). Mass spectrometry demonstrated, that compared to previously known cell-derived ECMs, the amniotic fluid cell-derived ECM of the invention contains matrix proteins found in all 3 germ layers and lacked specific proteins strongly associated with osteogenic lineages. Moreover, the ECM of the disclosure contain specific motifs, such as laminin, that are known to facilitate pluripotent cell adhesion and expansion.

Pluripotent stem cells (PSCs) can self-renew and differentiate into any of the three germ layers: ectoderm, endoderm, and mesoderm, from which all tissues and organs develop. Embryonic stem cells (ES) are currently the only known natural pluripotent stem cells. Induced pluripotent stem (iPSCs) cells also are PSCs. iPSCs are derived from cells generally taken from adult tissue or adult cells, and reprogrammed to the level of embryonic stem cells. Methods for producing iPSCs are known in the art.

Methods to expand/proliferate pluripotent stem cells (PSCs) include obtaining PSCs and culturing them in the presence of the amniotic fluid cell-derived ECM of the invention. The PSCs can be iPSCs or ES. Any seeding density may be used which allows cells to form a confluent monolayer immediately or after a period of time in culture. In some embodiments, the seeding density is about 10 cells/cm²—about 100,000 cells/cm², or about 100 cells/cm²-about 75,000 cells/cm², or about 500 cells/cm²-about 50,000 cells/cm², or about 500 cells/cm²-about 10,000 cells/cm², or about 500 cells/cm²-about 5,000 cells/cm², or about 500 cells/cm²-about 2,500 cells/cm², or about 1,000 cells/cm²-about 25,000 cells/cm², or about 2,000 cells/cm²-about 10,000 cells/cm², or about 3,000 cells/cm²-about 5000 cells/cm².

In some embodiments the PSCs are maintained in an undifferentiated state and maintain their stemness. Cell culture techniques suitable for proliferation of PSCs in culture are known in the art. Suitable commercially available culture media for stem cell proliferation includes, but is not limited to StemMACS™ iPS-Brew XF, available from Miltenyl Biotec. In some embodiments, no Rock inhibitor is used. Once cells begin to approach confluence (e.g., as determined by brightfield microscopy), cells can be passaged manually, by cutting large colonies into smaller colonies and then re-plate those by physically lifting them off the dish and placing them on a fresh plate of amniotic fluid cell-derived ECM. This procedure can be repeated indefinitely. In some embodiments disclosed is a method of proliferating pluripotent stem cells (PSCs) in culture, the method comprising culturing the PSCs in the presence of a cell-derived extracellular matrix (ECM) in a culture media thereby proliferating the PSCs, wherein the cell-derived ECM is derived in-vitro from cells isolated from amniotic fluid.

The methods of expanding/proliferating PSCs described supra also apply to the use of expanding/proliferating PSCs in culture in the presence of other perinatal cell-derived ECMs. In some embodiments, disclosed is a method of proliferating pluripotent stem cells (PSCs) in culture, the method comprising culturing the PSCs in the presence of a cell-derived extracellular matrix (ECM) in a culture media thereby proliferating the PSCs, wherein the cell-derived ECM is derived in-vitro from cells isolated from an umbilical cord or placenta tissue. In some embodiments, the cells isolated from the umbilical cord are from the cord blood and/or the Wharton's jelly. In other embodiments, the cells isolated from the placenta tissue are from the membrane sheets (amnion and/or chorion), the villi, and/or the blood.

Examples

The following examples are included to demonstrate certain non-limiting aspects of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the applicants to function well in the practice of the invention. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

A. Example 1—Production of an Amniotic Fluid Cell-Derived ECM (AFC-ECM)

Four amniotic fluid cell-derived ECMs (Matrix A, Matrix B, Matrix C, and Matrix D) were made using the following procedure: cells aseptically isolated from amniotic fluid collected from full term birth (>37 weeks gestational age) from 4 donors were seeded onto fibronectin coated tissue-culture treated flasks and cultured in Complete Media at 37° C., 5% CO₂and 90% RH in an incubator. The Complete Media was alpha Minimum Essential Media (aMEM) plus 2 mM L-Glutamine plus antibiotic-antimycotic plus 15% Fetal Bovine Serum.

At day 3-4, one-half of the complete medium was aspirated from the flasks and replaced with one-half of new Complete Media. The flasks were placed back into the incubator at the same conditions as stated above.

At day 7-8, the Complete Media was aspirated from the culture flasks and was replenished with Inducing Media. The flasks were placed back into the incubator at the same conditions as stated above. The Inducing Media was Complete Media plus 50 mM L-Ascorbic Acid.

At day 10-11, the Inducing Media was aspirated from the culture flasks and the ECM which had formed inside the flasks was washed one time with phosphate buffered saline (PBS). Then the PBS was aspirated from the flasks. An Extraction Buffer was added to the flasks and incubated for 7-10 minutes at RT to decellularize each ECM, then the Extraction Buffer was aspirated from the flasks. The Extraction Buffer was PBS containing 0.5% (v/v) TRITON-X100 and 20 mM ammonium hydroxide (NH₄OH).

Each of the decellularized ECMs in the flasks was washed three times with PBS followed by one wash with sterile water and then the sterile water was aspirated from the flasks. The four decellularized ECMs in the flasks were allowed to dry at RT and then stored at 4° C.

A photomicrograph of a Brightfield Image of an amniotic fluid cell-derived ECM (Matrix B) is shown in FIG. 1 at 100× power using a 10× objective lens. An atomic force photomicrograph of 3 representative 40×40 um sections of the amniotic fluid cell-derived ECM (Matrix B) and a bone marrow cell-derived ECM showing topography, adhesion, and stiffness is shown in FIG. 2. The bone marrow- and amniotic fluid- cell-derived ECMs are structurally and physically distinct. Quantification of adhesion and stiffness (elastic modulus) of bone marrow- and amniotic fluid- cell-derived ECMs show bone marrow ECM is 10-fold stiffer, and 3-fold less adhesive, relative to amniotic fluid ECM as shown in the scatter plots in FIG. 3a (Adhesion) and FIG. 3b (Stiffness) where BM=bone marrow cell-derive ECM, AD=amniotic fluid cell-derived ECM (Matrix B). Each point represents an independent point of measurement.

B. Example 2—Composition of Amniotic Fluid Cell-Derived ECM

The composition of the each of the amniotic fluid cell-derived ECMs produced in Example 1 was determined by mass spectrometry. The components with their spectral count and molecular weight are listed in Table 2.

TABLE 2

Amniotic Fluid Cell-Derived ECM (AFC-ECM) Components

Total Spectra Count

Matrix
Matrix
Matrix
Matrix

Protein
MW
A
B
C
D

Isoform 7 of Fibronectin OS = Homo sapiens OX = 9606
269
kDa
817
13965
1143
794

GN = FN1

Isoform 3 of Fibronectin OS = Homo sapiens OX = 9606
259
kDa
807
13836
1150
790

GN = FN1

Fibronectin OS = Homo sapiens OX = 9606 GN = FN1 PE = 1
263
kDa
802
13851
1138
781

SV = 4

Isoform 14 of Fibronectin OS = Homo sapiens OX = 9606
249
kDa
770
12625
1103
763

GN = FN1

Isoform 10 of Fibronectin OS = Homo sapiens OX = 9606
240
kDa
758
12506
1082
746

GN = FN1

Myosin-9 OS = Homo sapiens OX = 9606 GN = MYH9
227
kDa
564
3923
295
340

PE = 1 SV = 4

SWISS-PROT: P60712 (Bos taurus) Actin, cytoplasmic1
42
kDa
293
2496
450
395

Vimentin OS = Homo sapiens OX = 9606 GN = VIM PE = 1
54
kDa
263
1179
178
338

SV = 4

Neuroblast differentiation-associated protein AHNAK
629
kDa
250
803
17
184

OS = Homo sapiens OX = 9606 GN = AHNAK PE = 1 SV = 2

Histone H2B type 1-D OS = Homo sapiens OX = 9606
14
kDa
212
1121
176
187

GN = HIST1H2BD PE = 1 SV = 2

Isoform 2 of Filamin-A OS = Homo sapiens OX = 9606
280
kDa
212
342
12
143

GN = FLNA

Basement membrane-specific heparan sulfate
469
kDa
202
0
402
338

proteoglycan core protein OS = Homo sapiens OX = 9606

GN = HSPG2 PE = 1 SV = 4

Isoform 4 of Plectin OS = Homo sapiens OX = 9606
516
kDa
185
337
10
83

GN = PLEC

SWISS-PROT: P02769 (Bos taurus) Bovine serum
69
kDa
122
112
53
72

albumin precursor

Tubulin beta chain OS = Homo sapiens OX = 9606
50
kDa
117
0
36
92

GN = TUBB PE = 1 SV = 2

Spectrin alpha chain, non-erythrocytic 1 OS = Homo
285
kDa
107
342
10
78

sapiens OX = 9606 GN = SPTAN1 PE = 1 SV = 3

Tubulin beta-4B chain OS = Homo sapiens OX = 9606
50
kDa
107
0
34
84

GN = TUBB4B PE = 1 SV = 1

Isoform 3 of Spectrin alpha chain, non-erythrocytic 1
282
kDa
106
345
0
77

OS = Homo sapiens GN = SPTAN1

Histone H4 OS = Homo sapiens OX = 9606
11
kDa
100
1257
91
96

GN = HIST1H4A PE = 1 SV = 2

Tubulin beta-4A chain OS = Homo sapiens OX = 9606
50
kDa
99
0
31
76

GN = TUBB4A PE = 1 SV = 2

Protein-glutamine gamma-glutamyltransferase 2
77
kDa
94
188
73
25

OS = Homo sapiens OX = 9606 GN = TGM2 PE = 1 SV = 2

SWISS-PROT: P00761|TRYP_PIG Trypsin - Sus scrofa
24
kDa
94
362
121
96

(Pig).

Tubulin alpha-1B chain OS = Homo sapiens OX = 9606
50
kDa
93
295
37
86

GN = TUBA1B PE = 1 SV = 1

Isoform 2 of Clathrin heavy chain 1 OS = Homo sapiens
188
kDa
92
97
1
15

OX = 9606 GN = CLTC

Tubulin beta-2A chain OS = Homo sapiens OX = 9606
50
kDa
92
0
32
73

GN = TUBB2A PE = 1 SV = 1

Elongation factor 1-alpha 1 OS = Homo sapiens OX = 9606
50
kDa
89
132
14
70

GN = EEF1A1 PE = 1 SV = 1

Isoform 2 of Tubulin alpha-1A chain OS = Homo sapiens
46
kDa
88
305
34
82

OX = 9606 GN = TUBA1A

Talin-1 OS = Homo sapiens OX = 9606 GN = TLN1 PE = 1
270
kDa
88
109
4
41

SV = 3

Myosin-10 OS = Homo sapiens GN = MYH10 PE = 1 SV = 3
229
kDa
84
417
56
46

Spectrin beta chain, non-erythrocytic 1 OS = Homo
275
kDa
84
260
7
61

sapiens OX = 9606 GN = SPTBN1 PE = 1 SV = 2

Pyruvate kinase PKM OS = Homo sapiens OX = 9606
58
kDa
83
73
21
46

GN = PKM PE = 1 SV = 4

Tubulin alpha-1C chain OS = Homo sapiens OX = 9606
50
kDa
83
0
0
78

GN = TUBA1C PE = 1 SV = 1

Major vault protein OS = Homo sapiens OX = 9606
99
kDa
82
360
68
108

GN = MVP PE = 1 SV = 4

Actin, aortic smooth muscle OS = Homo sapiens
42
kDa
78
0
126
77

OX = 9606 GN = ACTA2 PE = 1 SV = 1

Actin, gamma-enteric smooth muscle OS = Homo sapiens
42
kDa
76
313
122
73

OX = 9606 GN = ACTG2 PE = 1 SV = 1

Alpha-actinin-4 OS = Homo sapiens OX = 9606
105
kDa
75
199
11
76

GN = ACTN4 PE = 1 SV = 2

Isoform 8 of Filamin-B OS = Homo sapiens OX = 9606
282
kDa
75
123
2
94

GN = FLNB

Tubulin alpha-4A chain OS = Homo sapiens OX = 9606
50
kDa
73
262
0
65

GN = TUBA4A PE = 1 SV = 1

Glyceraldehyde-3-phosphate dehydrogenase OS = Homo
36
kDa
71
145
24
66

sapiens OX = 9606 GN = GAPDH PE = 1 SV = 3

Cytoplasmic dynein 1 heavy chain 1 OS = Homo sapiens
532
kDa
65
49
0
5

OX = 9606 GN = DYNC1H1 PE = 1 SV = 5

Histone H2A.J OS = Homo sapiens OX = 9606 GN = H2AFJ
14
kDa
65
216
62
79

PE = 1 SV = 1

Serpin H1 OS = Homo sapiens OX = 9606 GN = SERPINH1
46
kDa
64
731
128
97

PE = 1 SV = 2

Histone H2A type 2-C OS = Homo sapiens OX = 9606
14
kDa
63
0
61
82

GN = HIST2H2AC PE = 1 SV = 4

Alpha-actinin-1 OS = Homo sapiens GN = ACTN1PE = 1
103
kDa
62
217
19
77

SV = 2

Histone H2AX OS = Homo sapiens OX = 9606
15
kDa
61
0
69
75

GN = H2AFX PE = 1 SV = 2

Tubulin beta-3 chain OS = Homo sapiens OX = 9606
50
kDa
58
194
28
53

GN = TUBB3 PE = 1 SV = 2

Endoplasmic reticulum chaperone BiP OS = Homo
72
kDa
57
0
35
46

sapiens OX = 9606 GN = HSPA5 PE = 1 SV = 2

Myosin regulatory light chain 12A OS = Homo sapiens
20
kDa
57
0
244
153

OX = 9606 GN = MYL12A PE = 1 SV = 1

Myosin regulatory light chain 12B OS = Homo sapiens
20
kDa
57
0
240
149

OX = 9606 GN = MYL12B PE = 1 SV = 2

Elongation factor 2 OS = Homo sapiens OX = 9606
95
kDa
53
72
3
45

GN = EEF2 PE = 1 SV = 4

Filamin-C OS = Homo sapiens OX = 9606 GN = FLNC
291
kDa
53
62
3
63

PE = 1 SV = 3

Histone H3.1 OS = Homo sapiens OX = 9606
15
kDa
53
0
24
33

GN = HIST1H3A PE = 1 SV = 2

60 kDa heat shock protein, mitochondrial OS = Homo
61
kDa
52
58
14
58

sapiens OX = 9606 GN = HSPD1 PE = 1 SV = 2

Tubulin beta-6 chain OS = Homo sapiens OX = 9606
50
kDa
52
0
23
52

GN = TUBB6 PE = 1 SV = 1

Isoform 4 of Collagen alpha-1(XII) chain OS = Homo
325
kDa
51
35
36
27

sapiens OX = 9606 GN = COL12A1

Nucleophosmin OS = Homo sapiens OX = 9606
33
kDa
48
103
15
43

GN = NPM1 PE = 1 SV = 2

Prelamin-A/C OS = Homo sapiens OX = 9606 GN = LMNA
74
kDa
48
149
20
39

PE = 1 SV = 1

Heat shock protein HSP 90-beta OS = Homo sapiens
83
kDa
47
0
3
31

OX = 9606 GN = HSP90AB1 PE = 1 SV = 4

Ras GTPase-activating-like protein IQGAP1 OS = Homo
189
kDa
47
0
11
36

sapiens OX = 9606 GN = IQGAP1 PE = 1 SV = 1

Heat shock cognate 71 kDa protein OS = Homo sapiens
71
kDa
46
130
28
56

OX = 9606 GN = HSPA8 PE = 1 SV = 1

Annexin A2 OS = Homo sapiens OX = 9606 GN = ANXA2
39
kDa
43
111
5
40

PE = 1 SV = 2

Isoform 2 of Collagen alpha-1(XVIII) chain OS = Homo
154
kDa
42
575
77
61

sapiens OX = 9606 GN = COL18A1

Myosin regulatory light polypeptide 9 OS = Homo sapiens
20
kDa
42
380
131
81

OX = 9606 GN = MYL9 PE = 1 SV = 4

Isoform 6 of Agrin OS = Homo sapiens OX = 9606
215
kDa
41
168
42
70

GN = AGRN

Histone H3.2 OS = Homo sapiens OX = 9606
15
kDa
40
0
17
25

GN = HIST2H3A PE = 1 SV = 3

Isoform 1 of Core histone macro-H2A.1 OS = Homo
39
kDa
40
450
43
49

sapiens OX = 9606 GN = H2AFY

ATP synthase subunit beta, mitochondrial OS = Homo
57
kDa
39
94
14
45

sapiens OX = 9606 GN = ATP5F1B PE = 1 SV = 3

T-complex protein 1 subunit alpha OS = Homo sapiens
60
kDa
39
0
25
36

OX = 9606 GN = TCP1 PE = 1 SV = 1

Isoform 2 of Heat shock protein HSP 90-alpha
98
kDa
38
80
1
20

OS = Homo sapiens GN = HSP90AA1

Transitional endoplasmic reticulum ATPase OS = Homo
89
kDa
38
86
1
37

sapiens OX = 9606 GN = VCP PE = 1 SV = 4

TREMBL: Q3KNV1; Q96GE1 Tax_Id = 9606
51
kDa
38
334
58
133

Gene_Symbol = KRT7 keratin 7

(Bos taurus) similar to alpha-2-macroglobulin isoform1
164
kDa
37
14
9
13

Heterogeneous nuclear ribonucleoprotein U OS = Homo
91
kDa
35
64
12
29

sapiens OX = 9606 GN = HNRNPU PE = 1 SV = 6

Histone H3.3 OS = Homo sapiens OX = 9606 GN = H3F3A
15
kDa
35
0
17
43

PE = 1 SV = 2

Microtubule-associated protein 4 OS = Homo sapiens
121
kDa
35
73
8
26

OX = 9606 GN = MAP4 PE = 1 SV = 3

Beta-actin-like protein 2 OS = Homo sapiens OX = 9606
42
kDa
34
147
42
31

GN = ACTBL2 PE = 1 SV = 2

Keratin, type I cytoskeletal 10 OS = Homo sapiens
59
kDa
34
464
32
37

OX = 9606 GN = KRT10 PE = 1 SV = 6

Ribosome-binding protein 1 OS = Homo sapiens
152
kDa
34
80
17
22

OX = 9606 GN = RRBP1 PE = 1 SV = 5

Cytoskeleton-associated protein 4 OS = Homo sapiens
66
kDa
33
139
30
35

OX = 9606 GN = CKAP4 PE = 1 SV = 2

DNA-dependent protein kinase catalytic subunit
469
kDa
33
10
0
5

OS = Homo sapiens OX = 9606 GN = PRKDC PE = 1 SV = 3

Adenylyl cyclase-associated protein 1 OS = Homo sapiens
52
kDa
32
33
2
37

OX = 9606 GN = CAP1 PE = 1 SV = 5

Keratin, type I cytoskeletal 9 OS = Homo sapiens
62
kDa
31
643
61
50

OX = 9606 GN = KRT9 PE = 1 SV = 3

Laminin subunit alpha-5 OS = Homo sapiens OX = 9606
400
kDa
31
50
7
13

GN = LAMA5 PE = 1 SV = 8

(Bos taurus) similar to fibulin-1 C isoform 1
77
kDa
30
71
40
18

60S ribosomal protein L4 OS = Homo sapiens OX = 9606
48
kDa
30
75
26
25

GN = RPL4 PE = 1 SV = 5

Alpha-enolase OS = Homo sapiens OX = 9606 GN = ENO1
47
kDa
30
61
3
26

PE = 1 SV = 2

ATP synthase subunit alpha, mitochondrial OS = Homo
60
kDa
30
52
12
34

sapiens OX = 9606 GN = ATP5F1A PE = 1 SV = 1

Heterogeneous nuclear ribonucleoprotein M OS = Homo
78
kDa
30
114
12
30

sapiens OX = 9606 GN = HNRNPM PE = 1 SV = 3

Histone H2A.V OS = Homo sapiens OX = 9606
14
kDa
30
131
23
34

GN = H2AFV PE = 1 SV = 3

Lysyl oxidase homolog 2 OS = Homo sapiens OX = 9606
87
kDa
30
320
94
52

GN = LOXL2 PE = 1 SV = 1

MICOS complex subunit MIC60 OS = Homo sapiens
84
kDa
30
98
20
36

OX = 9606 GN = IMMT PE = 1 SV = 1

SWISS-PROT: P12763 (Bos taurus) Alpha-2-HS-
38
kDa
30
42
18
19

glycoprotein precursor

Endoplasmin OS = Homo sapiens OX = 9606
92
kDa
29
71
3
22

GN = HSP90B1 PE = 1 SV = 1

TREMBL: Q0IIK2 (Bos taurus) Transferrin
78
kDa
29
15
2
16

Laminin subunit beta-1 OS = Homo sapiens OX = 9606
198
kDa
28
30
4
11

GN = LAMB1 PE = 1 SV = 2

T-complex protein 1 subunit beta OS = Homo sapiens
57
kDa
27
117
19
31

OX = 9606 GN = CCT2 PE = 1 SV = 4

T-complex protein 1 subunit delta OS = Homo sapiens
58
kDa
27
73
19
26

OX = 9606 GN = CCT4 PE = 1 SV = 4

Heterogeneous nuclear ribonucleoprotein K OS = Homo
51
kDa
26
28
3
26

sapiens OX = 9606 GN = HNRNPK PE = 1 SV = 1

Bifunctional glutamate/proline--tRNA ligase OS = Homo
171
kDa
25
20
0
1

sapiens OX = 9606 GN = EPRS PE = 1 SV = 5

Isoform 1 of Vinculin OS = Homo sapiens OX = 9606
117
kDa
25
25
1
26

GN = VCL

Isoform 2 of MICOS complex subunit MIC60 OS = Homo
83
kDa
25
99
17
34

sapiens OX = 9606 GN = IMMT

T-complex protein 1 subunit theta OS = Homo sapiens
60
kDa
25
100
21
30

OX = 9606 GN = CCT8 PE = 1 SV = 4

Isoform LCRMP-4 of Dihydropyrimidinase-related
74
kDa
24
11
4
40

protein 3 OS = Homo sapiens OX = 9606 GN = DPYSL3

Thrombospondin-1 OS = Homo sapiens OX = 9606
129
kDa
24
103
3
1

GN = THBS1 PE = 1 SV = 2

Isoform Short of 14-3-3 protein beta/alpha OS = Homo
28
kDa
23
18
2
14

sapiens OX = 9606 GN = YWHAB

Isoform Smooth muscle of Myosin light polypeptide 6
17
kDa
23
204
37
28

OS = Homo sapiens OX = 9606 GN = MYL6

Keratin, type I cytoskeletal 18 OS = Homo sapiens
48
kDa
23
376
99
120

OX = 9606 GN = KRT18 PE = 1 SV = 2

Keratin, type II cytoskeletal 8 OS = Homo sapiens
54
kDa
23
1404
107
155

OX = 9606 GN = KRT8 PE = 1 SV = 7

Lamin-B1 OS = Homo sapiens OX = 9606 GN = LMNB1
66
kDa
23
67
7
21

PE = 1 SV = 2

L-lactate dehydrogenase A chain OS = Homo sapiens
37
kDa
23
18
2
10

GN = LDHA PE = 1 SV = 2

Profilin-1 OS = Homo sapiens OX = 9606 GN = PFN1PE = 1
15
kDa
23
0
6
17

SV = 2

Protein disulfide-isomerase OS = Homo sapiens OX = 9606
57
kDa
23
0
6
19

GN = P4HB PE = 1 SV = 3

T-complex protein 1 subunit gamma OS = Homo sapiens
61
kDa
23
72
17
26

GN = CCT3 PE = 1 SV = 4

40S ribosomal protein S15 OS = Homo sapiens OX = 9606
17
kDa
22
0
26
38

GN = RPS15 PE = 1 SV = 2

ATP-citrate synthase OS = Homo sapiens OX = 9606
121
kDa
22
20
2
18

GN = ACLY PE = 1 SV = 3

Isoform 2 of Transgelin-2 OS = Homo sapiens OX = 9606
24
kDa
22
47
1
20

GN = TAGLN2

Versican core protein OS = Homo sapiens OX = 9606
373
kDa
22
188
33
27

GN = VCAN PE = 1 SV = 3

60S acidic ribosomal protein P0 OS = Homo sapiens
34
kDa
21
56
14
19

OX = 9606 GN = RPLP0 PE = 1 SV = 1

Histone H1.5 OS = Homo sapiens OX = 9606
23
kDa
21
53
11
20

GN = HIST1H1B PE = 1 SV = 3

Importin subunit beta-1 OS = Homo sapiens OX = 9606
97
kDa
21
19
1
6

GN = KPNB1 PE = 1 SV = 2

Isoform 2 of Fructose-bisphosphate aldolase A
45
kDa
21
37
0
21

OS = Homo sapiens OX = 9606 GN = ALDOA

Microtubule-associated protein 1B OS = Homo sapiens
271
kDa
21
104
0
22

OX = 9606 GN = MAP1B PE = 1 SV = 2

TREMBL: Q3SX09 (Bos taurus) similar to HBGprotein
22
kDa
21
26
11
9

5′-nucleotidase OS = Homo sapiens OX = 9606 GN = NT5E
63
kDa
20
129
21
17

PE = 1 SV = 1

60S ribosomal protein L3 OS = Homo sapiens OX = 9606
46
kDa
20
65
15
24

GN = RPL3 PE = 1 SV = 2

60S ribosomal protein L6 OS = Homo sapiens OX = 9606
33
kDa
20
0
19
25

GN = RPL6 PE = 1 SV = 3

ATP-dependent 6-phosphofructokinase, platelet type
86
kDa
20
9
0
18

OS = Homo sapiens OX = 9606 GN = PFKP PE = 1 SV = 2

Collagen alpha-1(I) chain OS = Homo sapiens OX = 9606
139
kDa
20
41
43
27

GN = COL1A1 PE = 1 SV = 5

T-complex protein 1 subunit eta OS = Homo sapiens
59
kDa
20
72
15
22

OX = 9606 GN = CCT7 PE = 1 SV = 2

Trifunctional enzyme subunit alpha, mitochondrial
83
kDa
20
78
16
13

OS = Homo sapiens OX = 9606 GN = HADHA PE = 1 SV = 2

40S ribosomal protein S7 OS = Homo sapiens OX = 9606
22
kDa
19
104
25
28

GN = RPS7 PE = 1 SV = 1

60S ribosomal protein L9 OS = Homo sapiens OX = 9606
22
kDa
19
0
14
21

GN = RPL9 PE = 1 SV = 1

Actin-related protein 3 OS = Homo sapiens OX = 9606
47
kDa
19
0
16
18

GN = ACTR3 PE = 1 SV = 3

Annexin A5 OS = Homo sapiens OX = 9606 GN = ANXA5
36
kDa
19
0
0
15

PE = 1 SV = 2

Calpain-2 catalytic subunit OS = Homo sapiens OX = 9606
80
kDa
19
4
0
8

GN = CAPN2 PE = 1 SV = 6

Heterogeneous nuclear ribonucleoprotein Al OS = Homo
39
kDa
19
55
10
23

sapiens OX = 9606 GN = HNRNPA1 PE = 1 SV = 5

Integrin beta-1 OS = Homo sapiens OX = 9606GN = ITGB1
88
kDa
19
16
4
18

PE = 1 SV = 2

Interleukin enhancer-binding factor 2 OS = Homo sapiens
43
kDa
19
0
4
15

OX = 9606 GN = ILF2 PE = 1 SV = 2

Isoform 2 of Nidogen-2 OS = Homo sapiens OX = 9606
141
kDa
19
55
0
3

GN = NID2

Matrin-3 OS = Homo sapiens OX = 9606 GN = MATR3
95
kDa
19
46
5
20

PE = 1 SV = 2

T-complex protein 1 subunit zeta OS = Homo sapiens
58
kDa
19
64
23
28

OX = 9606 GN = CCT6A PE = 1 SV = 3

40S ribosomal protein S2 OS = Homo sapiens OX = 9606
31
kDa
18
0
14
17

GN = RPS2 PE = 1 SV = 2

40S ribosomal protein S3 OS = Homo sapiens OX = 9606
27
kDa
18
82
19
20

GN = RPS3 PE = 1 SV = 2

Collagen alpha-2(IV) chain OS = Homo sapiens OX = 9606
168
kDa
18
209
44
33

GN = COL4A2 PE = 1 SV = 4

Epiplakin OS = Homo sapiens OX = 9606 GN = EPPK1
556
kDa
18
22
1
39

PE = 1 SV = 3

Heat shock 70 kDa protein 1A OS = Homo sapiens
70
kDa
18
31
0
23

OX = 9606 GN = HSPA1A PE = 1 SV = 1

Heterogeneous nuclear ribonucleoproteins C1/C2
34
kDa
18
52
6
22

OS = Homo sapiens OX = 9606 GN = HNRNPC PE = 1 SV = 4

Isoform 2 of Gelsolin OS = Homo sapiens OX = 9606
81
kDa
18
87
36
24

GN = GSN

Isoform 5 of Septin-9 OS = Homo sapiens OX = 9606
65
kDa
18
42
1
16

GN = SEPT9

Laminin subunit gamma-1 OS = Homo sapiens OX = 9606
178
kDa
18
48
0
6

GN = LAMC1 PE = 1 SV = 3

Nucleolin OS = Homo sapiens OX = 9606 GN = NCL PE = 1
77
kDa
18
58
8
16

SV = 3

Voltage-dependent anion-selective channel protein 1
31
kDa
18
50
4
19

OS = Homo sapiens OX = 9606 GN = VDAC1 PE = 1 SV = 2

X-ray repair cross-complementing protein 6 OS = Homo
70
kDa
18
33
2
14

sapiens OX = 9606 GN = XRCC6 PE = 1 SV = 2

Actin-related protein 2 OS = Homo sapiens OX = 9606
45
kDa
17
43
17
28

GN = ACTR2 PE = 1 SV = 1

Heat shock protein beta-1 OS = Homo sapiens OX = 9606
23
kDa
17
0
9
35

GN = HSPB1 PE = 1 SV = 2

Histone H1.4 OS = Homo sapiens OX = 9606
22
kDa
17
14
10
13

GN = HIST1H1E PE = 1 SV = 2

Isoform 2 of AP-2 complex subunit beta OS = Homo
106
kDa
17
33
1
15

sapiens OX = 9606 GN = AP2B1

Isoform 2 of Calnexin OS = Homo sapiens OX = 9606
72
kDa
17
21
1
19

GN = CANX

Isoform 2 of Dolichyl-diphosphooligosaccharid--protein
68
kDa
17
35
8
25

glycosyltransferase subunit 2 OS = Homo sapiens

OX = 9606 GN = RPN2

Moesin OS = Homo sapiens OX = 9606 GN = MSN PE = 1
68
kDa
17
61
3
15

SV = 3

Protein disulfide-isomerase A3 OS = Homo sapiens
57
kDa
17
26
0
14

OX = 9606 GN = PDIA3 PE = 1 SV = 4

Stress-70 protein, mitochondrial OS = Homo sapiens
74
kDa
17
33
0
10

OX = 9606 GN = HSPA9 PE = 1 SV = 2

SWISS-PROT: P34955 (Bos taurus) Alpha-1-
46
kDa
17
66
19
16

antiproteinase precursor

T-complex protein 1 subunit epsilon OS = Homo sapiens
60
kDa
17
110
18
22

OX = 9606 GN = CCT5 PE = 1 SV = 1

14-3-3 protein zeta/delta OS = Homo sapiens OX = 9606
28
kDa
16
35
4
19

GN = YWHAZ PE = 1 SV = 1

40S ribosomal protein S4, X isoform OS = Homo sapiens
30
kDa
16
77
20
20

OX = 9606 GN = RPS4X PE = 1 SV = 2

60S ribosomal protein L10 OS = Homo sapiens OX = 9606
25
kDa
16
27
7
12

GN = RPL10 PE = 1 SV = 4

Ezrin OS = Homo sapiens OX = 9606 GN = EZR PE = 1
69
kDa
16
43
4
23

SV = 4

High mobility group protein HMG-I/HMG-Y OS = Homo
12
kDa
16
52
7
11

sapiens OX = 9606 GN = HMGA1 PE = 1 SV = 3

Hypoxia up-regulated protein 1 OS = Homo sapiens
111
kDa
16
37
0
18

OX = 9606 GN = HYOU1 PE = 1 SV = 1

Isoform 2 of Ubiquitin-like modifier-activating enzyme 1
114
kDa
16
21
0
5

OS = Homo sapiens OX = 9606 GN = UBA1

Isoform 3 of Heterogeneous nuclear ribonucleoprotein Q
63
kDa
16
37
5
20

OS = Homo sapiens OX = 9606 GN = SYNCRIP

Nidogen-1 OS = Homo sapiens OX = 9606 GN = NID1
136
kDa
16
56
1
7

PE = 1 SV = 3

14-3-3 protein epsilon OS = Homo sapiens OX = 9606
29
kDa
15
26
3
16

GN = YWHAE PE = 1 SV = 1

40S ribosomal protein S5 OS = Homo sapiens OX = 9606
23
kDa
15
0
10
12

GN = RPS5 PE = 1 SV = 4

60S ribosomal protein L5 OS = Homo sapiens OX = 9606
34
kDa
15
0
16
16

GN = RPL5 PE = 1 SV = 3

60S ribosomal protein L7 OS = Homo sapiens OX = 9606
29
kDa
15
61
14
14

GN = RPL7 PE = 1 SV = 1

Caprin-1 OS = Homo sapiens OX = 9606 GN = CAPRIN1
78
kDa
15
18
0
14

PE = 1 SV = 2

Catenin alpha-1 OS = Homo sapiens OX = 9606
100
kDa
15
13
0
12

GN = CTNNA1 PE = 1 SV = 1

Eukaryotic initiation factor 4A-I OS = Homo sapiens
46
kDa
15
28
2
8

OX = 9606 GN = EIF4A1 PE = 1 SV = 1

Heterogeneous nuclear ribonucleoproteins A2/B1
37
kDa
15
58
6
20

OS = Homo sapiens OX = 9606 GN = HNRNPA2B1 PE = 1

SV = 2

Isoform 2 of Coatomer subunit alpha OS = Homo sapiens
139
kDa
15
8
0
0

OX = 9606 GN = COPA

Isoform 2 of Protein disulfide-isomerase A6 OS = Homo
54
kDa
15
23
0
15

sapiens OX = 9606 GN = PDIA6

Isoform 3 of Septin-2 OS = Homo sapiens OX = 9606
43
kDa
15
55
6
16

GN = SEPT2

Staphylococcal nuclease domain-containing protein 1
102
kDa
15
33
0
6

OS = Homo sapiens OX = 9606 GN = SND1 PE = 1 SV = 1

Triosephosphate isomerase OS = Homo sapiens OX = 9606
31
kDa
15
15
0
11

GN = TPI1 PE = 1 SV = 3

UDP-glucose 6-dehydrogenase OS = Homo sapiens
55
kDa
15
24
2
15

OX = 9606 GN = UGDH PE = 1 SV = 1

ADP/ATP translocase 2 OS = Homo sapiens OX = 9606
33
kDa
14
27
9
17

GN = SLC25A5 PE = 1 SV = 7

ATP-dependent RNA helicase A OS = Homo sapiens
141
kDa
14
25
1
9

OX = 9606 GN = DHX9 PE = 1 SV = 4

Cofilin-1 OS = Homo sapiens OX = 9606 GN = CFL1 PE = 1
19
kDa
14
0
4
11

SV = 3

eIF-2-alpha kinase activator GCN1 OS = Homo sapiens
293
kDa
14
0
0
6

OX = 9606 GN = GCN1 PE = 1 SV = 6

Isoform 2 of Kinectin OS = Homo sapiens OX = 9606
150
kDa
14
62
1
8

GN = KTN1

Isoform 2 of Spliceosome RNA helicase DDX39B
51
kDa
14
25
1
12

OS = Homo sapiens OX = 9606 GN = DDX39B

Isoleucine--tRNA ligase, cytoplasmic OS = Homo sapiens
145
kDa
14
0
0
0

OX = 9606 GN = IARS PE = 1 SV = 2

Keratin, type II cytoskeletal 2 epidermal OS = Homo
65
kDa
14
123
28
21

sapiens OX = 9606 GN = KRT2 PE = 1 SV = 2

Ribonuclease inhibitor OS = Homo sapiens OX = 9606
50
kDa
14
0
1
8

GN = RNH1 PE = 1 SV = 2

SWISS-PROT: P02070 (Bos taurus) Hemoglobin subunit
16
kDa
14
0
0
0

beta

SWISS-PROT: Q9DCV7 Tax_Id = 10090
51
kDa
14
0
14
18

Gene_Symbol = Krt7 Keratin, type II cytoskeletal 7

Tubulointerstitial nephritis antigen-like OS = Homo
52
kDa
14
173
78
38

sapiens OX = 9606 GN = TINAGL1 PE = 1 SV = 1

26S proteasome non-ATPase regulatory subunit 2
100
kDa
13
18
0
10

OS = Homo sapiens OX = 9606 GN = PSMD2 PE = 1 SV = 3

40S ribosomal protein S8 OS = Homo sapiens OX = 9606
24
kDa
13
0
9
15

GN = RPS8 PE = 1 SV = 2

60S ribosomal protein L23 OS = Homo sapiens OX = 9606
15
kDa
13
0
14
10

GN = RPL23 PE = 1 SV = 1

60S ribosomal protein L7a OS = Homo sapiens OX = 9606
30
kDa
13
68
12
14

GN = RPL7A PE = 1 SV = 2

ADP/ATP translocase 3 OS = Homo sapiens OX = 9606
33
kDa
13
0
8
18

GN = SLC25A6 PE = 1 SV = 4

Arginine--tRNA ligase, cytoplasmic OS = Homo sapiens
75
kDa
13
33
0
5

OX = 9606 GN = RARS PE = 1 SV = 2

Calpain small subunit 1 OS = Homo sapiens OX = 9606
28
kDa
13
0
0
22

GN = CAPNS1 PE = 1 SV = 1

Glycine--tRNA ligase OS = Homo sapiens OX = 9606
83
kDa
13
0
1
6

GN = GARS PE = 1 SV = 3

Isoform 2 of Extended synaptotagmin-1 OS = Homo
124
kDa
13
21
1
17

sapiens OX = 9606 GN = ESYT1

Isoform 2 of Nuclear mitotic apparatus protein 1
237
kDa
13
18
0
2

OS = Homo sapiens OX = 9606 GN = NUMA1

Isoform 2 of Tropomyosin beta chain OS = Homo sapiens
33
kDa
13
122
33
24

OX = 9606 GN = TPM2

Isoform 7 of Interleukin enhancer-binding factor 3
96
kDa
13
31
0
13

OS = Homo sapiens GN = ILF3

Isoform Beta-1 of DNA topoisomerase 2-beta OS = Homo
183
kDa
13
97
3
3

sapiens OX = 9606 GN = TOP2B

Lamin-B2 OS = Homo sapiens OX = 9606 GN = LMNB2
70
kDa
13
53
8
19

PE = 1 SV = 4

L-lactate dehydrogenase B chain OS = Homo sapiens
37
kDa
13
0
0
6

OX = 9606 GN = LDHB PE = 1 SV = 2

Nucleoprotein TPR OS = Homo sapiens OX = 9606
267
kDa
13
15
1
3

GN = TPR PE = 1 SV = 3

Receptor of activated protein C kinase 1 OS = Homo
35
kDa
13
0
1
12

sapiens OX = 9606 GN = RACK1 PE = 1 SV = 3

Serine protease HTRA1 OS = Homo sapiens OX = 9606
51
kDa
13
0
15
1

GN = HTRA1 PE = 1 SV = 1

Serine/threonine-protein phosphatase 2A 65 kDa
65
kDa
13
0
0
10

regulatory subunit A alpha isoform OS = Homo sapiens

OX = 9606 GN = PPP2R1A PE = 1 SV = 4

X-ray repair cross-complementing protein 5 OS = Homo
83
kDa
13
0
2
15

sapiens OX = 9606 GN = XRCC5 PE = 1 SV = 3

14-3-3 protein theta OS = Homo sapiens OX = 9606
28
kDa
12
0
2
12

GN = YWHAQ PE = 1 SV = 1

40S ribosomal protein S12 OS = Homo sapiens OX = 9606
15
kDa
12
0
1
9

GN = RPS12 PE = 1 SV = 3

Cytoplasmic dynein 1 light intermediate chain 2
54
kDa
12
12
3
19

OS = Homo sapiens OX = 9606 GN = DYNC1LI2 PE = 1

SV = 1

Glutathione S-transferase P OS = Homo sapiens OX = 9606
23
kDa
12
0
2
13

GN = GSTP1 PE = 1 SV = 2

Isoform 2 of Septin-7 OS = Homo sapiens OX = 9606
51
kDa
12
31
0
12

GN = SEPT7

Isoform 3 of Unconventional myosin-Ic OS = Homo
120
kDa
12
64
9
8

sapiens OX = 9606 GN = MYO1C

Peptidyl-prolyl cis-trans isomerase A OS = Homo sapiens
18
kDa
12
36
3
11

OX = 9606 GN = PPIA PE = 1 SV = 2

Polyadenylate-binding protein 1 OS = Homo sapiens
71
kDa
12
22
0
15

OX = 9606 GN = PABPC1 PE = 1 SV = 2

Rho-related GTP-binding protein RhoC OS = Homo
22
kDa
12
0
5
12

sapiens OX = 9606 GN = RHOC PE = 1 SV = 1

Ribosomal L1 domain-containing protein 1 OS = Homo
55
kDa
12
18
8
12

sapiens OX = 9606 GN = RSL1D1 PE = 1 SV = 3

Transgelin OS = Homo sapiens OX = 9606 GN = TAGLN
23
kDa
12
41
10
23

PE = 1 SV = 4

14-3-3 protein gamma OS = Homo sapiens OX = 9606
28
kDa
11
0
1
14

GN = YWHAG PE = 1 SV = 2

26S proteasome regulatory subunit 6A OS = Homo
47
kDa
11
0
0
17

sapiens OX = 9606 GN = PSMC3 PE = 1 SV = 1

40S ribosomal protein S17 OS = Homo sapiens OX = 9606
16
kDa
11
67
20
16

GN = RPS17 PE = 1 SV = 2

60S ribosomal protein L10a OS = Homo sapiens
25
kDa
11
0
11
17

OX = 9606 GN = RPL10A PE = 1 SV = 2

60S ribosomal protein L12 OS = Homo sapiens OX = 9606
18
kDa
11
36
10
9

GN = RPL12 PE = 1 SV = 1

ADP-ribosylation factor 4 OS = Homo sapiens OX = 9606
21
kDa
11
0
8
14

GN = ARF4 PE = 1 SV = 3

Annexin A6 OS = Homo sapiens OX = 9606 GN = ANXA6
76
kDa
11
15
0
9

PE = 1 SV = 3

ATP synthase subunit O, mitochondrial OS = Homo
23
kDa
11
0
5
10

sapiens OX = 9606 GN = ATP5PO PE = 1 SV = 1

Core histone macro-H2A.2 OS = Homo sapiens OX = 9606
40
kDa
11
226
28
21

GN = H2AFY2 PE = 1 SV = 3

Dolichyl-diphosphooligosaccharide--protein
69
kDa
11
43
7
18

glycosyltransferase subunit 1 OS = Homo sapiens

OX = 9606 GN = RPN1 PE = 1 SV = 1

Elongation factor 1-gamma OS = Homo sapiens OX = 9606
50
kDa
11
29
0
8

GN = EEF1G PE = 1 SV = 3

Guanine nucleotide-binding protein G(i) subunit alpha-2
40
kDa
11
45
6
8

OS = Homo sapiens OX = 9606 GN = GNAI2 PE = 1 SV = 3

Heterogeneous nuclear ribonucleoprotein R OS = Homo
71
kDa
11
17
4
12

sapiens OX = 9606 GN = HNRNPR PE = 1 SV = 1

Isoform 2 of Probable ATP-dependent RNA helicase
72
kDa
11
17
0
9

DDX17 OS = Homo sapiens OX = 9606 GN = DDX17

Isoform 3 of Tropomyosin alpha-1 chain OS = Homo
33
kDa
11
181
46
37

sapiens OX = 9606 GN = TPM1

Isoform 4 of Caldesmon OS = Homo sapiens OX = 9606
63
kDa
11
51
10
32

GN = CALD1

Leucine--tRNA ligase, cytoplasmic OS = Homo sapiens
134
kDa
11
3
0
0

GN = LARS PE = 1 SV = 2

Phosphoglycerate kinase 1 OS = Homo sapiens OX = 9606
45
kDa
11
10
0
7

GN = PGK1 PE = 1 SV = 3

Polypyrimidine tract-binding protein 1 OS = Homo
57
kDa
11
33
1
20

sapiens OX = 9606 GN = PTBP1 PE = 1 SV = 1

Rab GDP dissociation inhibitor beta OS = Homo sapiens
51
kDa
11
17
0
10

OX = 9606 GN = GDI2 PE = 1 SV = 2

Reticulon-4 OS = Homo sapiens GN = RTN4 PE = 1 SV = 2
130
kDa
11
15
0
9

Serine hydroxymethyltransferase, mitochondrial
56
kDa
11
6
0
3

OS = Homo sapiens GN = SHMT2 PE = 1 SV = 3

Serine/threonine-protein phosphatase PP1-alpha catalytic
38
kDa
11
23
3
10

subunit OS = Homo sapiens OX = 9606 GN = PPP1CA

PE = 1 SV = 1

Splicing factor, proline- and glutamine-rich OS = Homo
76
kDa
11
43
5
18

sapiens OX = 9606 GN = SFPQ PE = 1 SV = 2

SWISS-PROT: Q3MHN5 (Bos taurus) Vitamin D-
53
kDa
11
15
2
4

binding protein precursor

Tenascin OS = Homo sapiens GN = TNC PE = 1 SV = 3
241
kDa
11
409
60
72

Threonine--tRNA ligase, cytoplasmic OS = Homo sapiens
83
kDa
11
10
0
3

OX = 9606 GN = TARS PE = 1 SV = 3

Tropomyosin alpha-4 chain OS = Homo sapiens OX = 9606
29
kDa
11
89
21
20

GN = TPM4 PE = 1 SV = 3

14-3-3 protein eta OS = Homo sapiens OX = 9606
28
kDa
10
0
1
10

GN = YWHAH PE = 1 SV = 4

26S proteasome regulatory subunit 6B OS = Homo sapiens
47
kDa
10
13
3
10

OX = 9606 GN = PSMC4 PE = 1 SV = 2

60S ribosomal protein L18 OS = Homo sapiens
19
kDa
10
26
7
9

GN = RPL18 PE = 1 SV = 1

Actin-related protein 2/3 complex subunit 2 OS = Homo
34
kDa
10
53
14
11

sapiens OX = 9606 GN = ARPC2 PE = 1 SV = 1

A-kinase anchor protein 12 OS = Homo sapiens OX = 9606
191
kDa
10
46
0
5

GN = AKAP12 PE = 1 SV = 4

Asparagine--tRNA ligase, cytoplasmic OS = Homo
63
kDa
10
10
0
1

sapiens OX = 9606 GN = NARS PE = 1 SV = 1

Aspartate--tRNA ligase, cytoplasmic OS = Homo sapiens
57
kDa
10
22
3
9

OX = 9606 GN = DARS PE = 1 SV = 2

Dolichyl-diphosphooligosaccharide--protein
51
kDa
10
13
6
17

glycosyltransferase 48 kDa subunit OS = Homo sapiens

OX = 9606 GN = DDOST PE = 1 SV = 4

Erlin-2 OS = Homo sapiens OX = 9606 GN = ERLIN2 PE = 1
38
kDa
10
39
4
11

SV = 1

Fatty acid synthase OS = Homo sapiens OX = 9606
273
kDa
10
0
0
2

GN = FASN PE = 1 SV = 3

Heterogeneous nuclear ribonucleoprotein A3 OS = Homo
40
kDa
10
25
7
8

sapiens OX = 9606 GN = HNRNPA3 PE = 1 SV = 2

Isoform 3 of Exportin-2 OS = Homo sapiens OX = 9606
108
kDa
10
2
2
3

GN = CSE1L

Isoform B of AP-1 complex subunit beta-1 OS = Homo
104
kDa
10
0
0
11

sapiens OX = 9606 GN = AP1B1

Leucine-rich PPR motif-containing protein,
158
kDa
10
5
0
0

mitochondrial OS = Homo sapiens OX = 9606

GN = LRPPRC PE = 1 SV = 3

Non-POU domain-containing octamer-binding protein
54
kDa
10
44
3
20

OS = Homo sapiens OX = 9606 GN = NONO PE = 1 SV = 4

Nucleolar protein 56 OS = Homo sapiens OX = 9606
66
kDa
10
18
1
2

GN = NOP56 PE = 1 SV = 4

Peroxidasin homolog OS = Homo sapiens OX = 9606
165
kDa
10
146
36
28

GN = PXDN PE = 1 SV = 2

Stomatin-like protein 2, mitochondrial OS = Homo sapiens
39
kDa
10
18
3
10

OX = 9606 GN = STOML2 PE = 1 SV = 1

SWISS-PROT: P01966 (Bos taurus) Hemoglobin subunit
15
kDa
10
34
12
10

alpha

SWISS-PROT: Q3SZ57 (Bos taurus) Alpha-fetoprotein
69
kDa
10
11
6
7

precursor

Transforming protein RhoA OS = Homo sapiens
22
kDa
10
0
4
10

OX = 9606 GN = RHOA PE = 1 SV = 1

40S ribosomal protein SA OS = Homo sapiens OX = 9606
33
kDa
9
0
1
10

GN = RPSA PE = 1 SV = 1

60S ribosomal protein L13 OS = Homo sapiens OX = 9606
24
kDa
9
32
12
12

GN = RPL13 PE = 1 SV = 4

60S ribosomal protein L8 OS = Homo sapiens OX = 9606
28
kDa
9
0
7
9

GN = RPL8 PE = 1 SV = 2

Aldehyde dehydrogenase X, mitochondrial OS = Homo
57
kDa
9
14
4
11

sapiens OX = 9606 GN = ALDH1B1 PE = 1 SV = 3

ATP-dependent RNA helicase DDX3X OS = Homo
73
kDa
9
18
5
11

sapiens OX = 9606 GN = DDX3X PE = 1 SV = 3

Calreticulin OS = Homo sapiens OX = 9606 GN = CALR
48
kDa
9
44
4
11

PE = 1 SV = 1

D-3-phosphoglycerate dehydrogenase OS = Homo sapiens
57
kDa
9
0
0
2

OX = 9606 GN = PHGDH PE = 1 SV = 4

F-actin-capping protein subunit alpha-1 OS = Homo
33
kDa
9
0
18
15

sapiens OX = 9606 GN = CAPZA1 PE = 1 SV = 3

Galectin-1 OS = Homo sapiens OX = 9606 GN = LGALS1
15
kDa
9
0
3
6

PE = 1 SV = 2

GTP-binding nuclear protein Ran OS = Homo sapiens
24
kDa
9
0
6
11

OX = 9606 GN = RAN PE = 1 SV = 3

Heterochromatin protein 1-binding protein 3 OS = Homo
61
kDa
9
24
4
7

sapiens OX = 9606 GN = HP1BP3 PE = 1 SV = 1

Isoform 1 of Voltage-dependent anion-selective channel
33
kDa
9
19
1
5

protein 2 OS = Homo sapiens OX = 9606 GN = VDAC2

Isoform 2 of Eukaryotic translation initiation factor 3
163
kDa
9
10
0
11

subunit A OS = Homo sapiens OX = 9606 GN = EIF3A

Isoform 2 of Glutamine--tRNA ligase OS = Homo sapiens
87
kDa
9
16
0
4

OX = 9606 GN = QARS

Isoform 2 of Tropomyosin alpha-3 chain OS = Homo
29
kDa
9
99
16
17

sapiens OX = 9606 GN = TPM3

Isoform 3 of Protein AHNAK2 OS = Homo sapiens
606
kDa
9
0
0
1

OX = 9606 GN = AHNAK2

Isoform D of Eukaryotic translation initiation factor 4
159
kDa
9
7
0
0

gamma 1 OS = Homo sapiens OX = 9606 GN = EIF4G1

KH domain-containing, RNA-binding, signal
48
kDa
9
24
5
9

transduction-associated protein 1 OS = Homo sapiens

OX = 9606 GN = KHDRBS1 PE = 1 SV = 1

Methionine--tRNA ligase, cytoplasmic OS = Homo
101
kDa
9
1
0
0

sapiens OX = 9606 GN = MARS PE = 1 SV = 2

Myeloid-associated differentiation marker OS = Homo
35
kDa
9
0
16
12

sapiens OX = 9606 GN = MYADM PE = 1 SV = 2

Neutral alpha-glucosidase AB OS = Homo sapiens
107
kDa
9
21
0
13

OX = 9606 GN = GANAB PE = 1 SV = 3

Peroxiredoxin-5, mitochondrial OS = Homo sapiens
22
kDa
9
6
0
5

OX = 9606 GN = PRDX5 PE = 1 SV = 4

Serine--tRNA ligase, cytoplasmic OS = Homo sapiens
59
kDa
9
0
0
9

OX = 9606 GN = SARS PE = 1 SV = 3

Tryptophan--tRNA ligase, cytoplasmic OS = Homo
53
kDa
9
6
1
7

sapiens OX = 9606 GN = WARS PE = 1 SV = 2

Vacuolar protein sorting-associated protein 35 OS = Homo
92
kDa
9
5
0
4

sapiens OX = 9606 GN = VPS35 PE = 1 SV = 2

26S proteasome non-ATPase regulatory subunit 3
61
kDa
8
21
0
6

OS = Homo sapiens OX = 9606 GN = PSMD3 PE = 1 SV = 2

40S ribosomal protein S16 OS = Homo sapiens OX = 9606
16
kDa
8
0
9
7

GN = RPS16 PE = 1 SV = 2

40S ribosomal protein S6 OS = Homo sapiens OX = 9606
29
kDa
8
0
5
11

GN = RPS6 PE = 1 SV = 1

40S ribosomal protein S9 OS = Homo sapiens OX = 9606
23
kDa
8
54
11
10

GN = RPS9 PE = 1 SV = 3

ADP/ATP translocase 1 OS = Homo sapiens OX = 9606
33
kDa
8
0
0
12

GN = SLC25A4 PE = 1 SV = 4

Annexin A1 OS = Homo sapiens OX = 9606 GN = ANXA1
39
kDa
8
0
0
8

PE = 1 SV = 2

ATP-dependent RNA helicase DDX1 OS = Homo sapiens
82
kDa
8
15
2
10

OX = 9606 GN = DDX1 PE = 1 SV = 2

Coatomer subunit gamma-1 OS = Homo sapiens
98
kDa
8
9
1
6

OX = 9606 GN = COPG1 PE = 1 SV = 1

Elongation factor Tu, mitochondrial OS = Homo sapiens
50
kDa
8
0
0
0

OX = 9606 GN = TUFM PE = 1 SV = 2

Erythrocyte band 7 integral membrane protein OS = Homo
32
kDa
8
6
2
3

sapiens OX = 9606 GN = STOM PE = 1 SV = 3

Eukaryotic translation initiation factor 2 subunit 3
51
kDa
8
0
3
12

OS = Homo sapiens OX = 9606 GN = EIF2S3 PE = 1 SV = 3

Flotillin-1 OS = Homo sapiens OX = 9606 GN = FLOT1
47
kDa
8
25
1
4

PE = 1 SV = 3

Heterogeneous nuclear ribonucleoprotein L OS = Homo
64
kDa
8
11
0
5

sapiens OX = 9606 GN = HNRNPL PE = 1 SV = 2

Isoform 2 of Ankycorbin OS = Homo sapiens OX = 9606
110
kDa
8
38
2
5

GN = RAI14

Isoform 2 of Bifunctional purine biosynthesis protein
65
kDa
8
5
0
4

PURH OS = Homo sapiens OX = 9606 GN = ATIC

Isoform 2 of Eukaryotic translation initiation factor 5A-1
20
kDa
8
14
1
7

OS = Homo sapiens OX = 9606 GN = EIF5A

Isoform 2 of Golgi apparatus protein 1 OS = Homo
137
kDa
8
4
9
1

sapiens OX = 9606 GN = GLG1

Isoform 2 of Poly(rC)-binding protein 2 OS = Homo
39
kDa
8
4
0
4

sapiens OX = 9606 GN = PCBP2

Isoform 3 of Heterogeneous nuclear ribonucleoprotein
33
kDa
8
20
6
11

D0 OS = Homo sapiens OX = 9606 GN = HNRNPD

Isoform B of Phosphate carrier protein, mitochondrial
40
kDa
8
7
5
8

OS = Homo sapiens OX = 9606 GN = SLC25A3

Kinesin-1 heavy chain OS = Homo sapiens OX = 9606
110
kDa
8
5
0
3

GN = KIF5B PE = 1 SV = 1

Malate dehydrogenase, mitochondrial OS = Homo sapiens
36
kDa
8
17
0
13

OX = 9606 GN = MDH2 PE = 1 SV = 3

Mitochondrial carrier homolog 2 OS = Homo sapiens
33
kDa
8
0
2
4

OX = 9606 GN = MTCH2 PE = 1 SV = 1

Pre-mRNA-processing factor 19 OS = Homo sapiens
55
kDa
8
0
0
14

OX = 9606 GN = PRPF19 PE = 1 SV = 1

Prohibitin OS = Homo sapiens OX = 9606 GN = PHB PE = 1
30
kDa
8
14
2
15

SV = 1

Protein transport protein Sec23A OS = Homo sapiens
86
kDa
8
9
1
10

OX = 9606 GN = SEC23A PE = 1 SV = 2

Protein transport protein Sec61 subunit alpha isoform 1
52
kDa
8
2
1
5

OS = Homo sapiens OX = 9606 GN = SEC61A1 PE = 1 SV = 2

Septin-11 OS = Homo sapiens OX = 9606 GN = SEPT11
49
kDa
8
27
0
9

PE = 1 SV = 3

Small nuclear ribonucleoprotein Sm D1 OS = Homo
13
kDa
8
0
6
7

sapiens OX = 9606 GN = SNRPD1 PE = 1 SV = 1

SWISS-PROT: P15497 (Bos taurus) Apolipoprotein A-I
30
kDa
8
21
6
4

precursor

THO complex subunit 4 OS = Homo sapiens OX = 9606
27
kDa
8
37
7
11

GN = ALYREF PE = 1 SV = 3

TREMBL: Q3ZBS7 (Bos taurus) Vitronectin
54
kDa
8
26
12
11

Ubiquitin-40S ribosomal protein S27a OS = Homo sapiens
18
kDa
8
0
13
10

OX = 9606 GN = RPS27A PE = 1 SV = 2

26S proteasome non-ATPase regulatory subunit 12
53
kDa
7
6
0
2

OS = Homo sapiens OX = 9606 GN = PSMD12 PE = 1 SV = 3

26S proteasome regulatory subunit 8 OS = Homo sapiens
46
kDa
7
6
0
12

OX = 9606 GN = PSMC5 PE = 1 SV = 1

40S ribosomal protein S14 OS = Homo sapiens OX = 9606
16
kDa
7
40
13
9

GN = RPS14 PE = 1 SV = 3

40S ribosomal protein S19 OS = Homo sapiens OX = 9606
16
kDa
7
0
12
15

GN = RPS19 PE = 1 SV = 2

40S ribosomal protein S23 OS = Homo sapiens OX = 9606
16
kDa
7
0
4
12

GN = RPS23 PE = 1 SV = 3

60S ribosomal protein L30 OS = Homo sapiens OX = 9606
13
kDa
7
0
8
8

GN = RPL30 PE = 1 SV = 2

ADP-ribosylation factor 3 OS = Homo sapiens OX = 9606
21
kDa
7
11
7
7

GN = ARF3 PE = 1 SV = 2

Aminoacyl tRNA synthase complex-interacting
35
kDa
7
0
0
6

multifunctional protein 2 OS = Homo sapiens OX = 9606

GN = AIMP2 PE = 1 SV = 2

CAD protein OS = Homo sapiens OX = 9606 GN = CAD
243
kDa
7
0
0
0

PE = 1 SV = 3

Catenin beta-1 OS = Homo sapiens OX = 9606
85
kDa
7
3
0
6

GN = CTNNB1 PE = 1 SV = 1

Cell division control protein 42 homolog OS = Homo
21
kDa
7
0
2
11

sapiens OX = 9606 GN = CDC42 PE = 1 SV = 2

Chloride intracellular channel protein 1 OS = Homo
27
kDa
7
0
0
5

sapiens OX = 9606 GN = CLIC1 PE = 1 SV = 4

Coatomer subunit beta OS = Homo sapiens OX = 9606
107
kDa
7
5
0
1

GN = COPB1 PE = 1 SV = 3

Eukaryotic initiation factor 4A-III OS = Homo sapiens
47
kDa
7
20
4
8

OX = 9606 GN = EIF4A3 PE = 1 SV = 4

Heterogeneous nuclear ribonucleoprotein H OS = Homo
51
kDa
7
23
1
9

sapiens OX = 9606 GN = HNRNPH1 PE = 1 SV = 1

Importin-5 OS = Homo sapiens OX = 9606 GN = IPO5
124
kDa
7
5
0
3

PE = 1 SV = 4

Inhibitor of nuclear factor kappa-B kinase-interacting
39
kDa
7
7
6
7

protein OS = Homo sapiens OX = 9606 GN = IKBIP PE = 1

SV = 1

Isoform 2 of 26S proteasome non-ATPase regulatory
48
kDa
7
12
0
5

subunit 11 OS = Homo sapiens OX = 9606 GN = PSMD11

Isoform 2 of F-actin-capping protein subunit beta
31
kDa
7
46
10
5

OS = Homo sapiens OX = 9606 GN = CAPZB

Isoform 2 of Heterogeneous nuclear ribonucleoprotein D-
34
kDa
7
8
0
7

like OS = Homo sapiens OX = 9606 GN = HNRNPDL

Isoform 2 of Integrin alpha-3 OS = Homo sapiens
119
kDa
7
2
0
5

OX = 9606 GN = ITGA3

Isoform 2 of Nucleolar RNA helicase 2 OS = Homo
80
kDa
7
16
2
7

sapiens OX = 9606 GN = DDX21

Isoform 2 of PDZ and LIM domain protein 7 OS = Homo
47
kDa
7
13
0
5

sapiens OX = 9606 GN = PDLIM7

Isoform 2 of Spermine synthase OS = Homo sapiens
35
kDa
7
2
0
6

OX = 9606 GN = SMS

Isoform 2 of Transketolase OS = Homo sapiens OX = 9606
69
kDa
7
29
0
9

GN = TKT

Isoform 3 of 116 kDa U5 small nuclear ribonucleoprotein
108
kDa
7
6
0
9

component OS = Homo sapiens OX = 9606 GN = EFTUD2

Isoform 3 of 60S ribosomal protein L17 OS = Homo
26
kDa
7
54
5
8

sapiens OX = 9606 GN = RPL17

Isoform 3 of Integrin alpha-V OS = Homo sapiens
111
kDa
7
22
2
12

OX = 9606 GN = ITGAV

Isoform SV3 of Supervillin OS = Homo sapiens OX = 9606
245
kDa
7
46
0
1

GN = SVIL

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
43
kDa
7
12
1
7

subunit 9, mitochondrial OS = Homo sapiens OX = 9606

GN = NDUFA9 PE = 1 SV = 2

Peroxiredoxin-1 OS = Homo sapiens OX = 9606
22
kDa
7
0
0
7

GN = PRDX1 PE = 1 SV = 1

Poly(rC)-binding protein 1 OS = Homo sapiens OX = 9606
37
kDa
7
0
0
2

GN = PCBP1 PE = 1 SV = 2

Pre-mRNA-processing-splicing factor 8 OS = Homo
274
kDa
7
6
1
3

sapiens OX = 9606 GN = PRPF8 PE = 1 SV = 2

Probable ATP-dependent RNA helicase DDX5
69
kDa
7
25
7
19

OS = Homo sapiens OX = 9606 GN = DDX5 PE = 1 SV = 1

Prohibitin-2 OS = Homo sapiens OX = 9606 GN = PHB2
33
kDa
7
25
5
12

PE = 1 SV = 2

Protein disulfide-isomerase A4 OS = Homo sapiens
73
kDa
7
4
0
4

OX = 9606 GN = PDIA4 PE = 1 SV = 2

Ras GTPase-activating protein-binding protein 1
52
kDa
7
19
2
8

OS = Homo sapiens OX = 9606 GN = G3BP1 PE = 1 SV = 1

Ras-related protein Rab-1B OS = Homo sapiens OX = 9606
22
kDa
7
0
0
8

GN = RAB1B PE = 1 SV = 1

RNA-binding motif protein, X chromosome OS = Homo
42
kDa
7
22
5
13

sapiens OX = 9606 GN = RBMX PE = 1 SV = 3

Splicing factor 3B subunit 1 OS = Homo sapiens
146
kDa
7
16
1
3

OX = 9606 GN = SF3B1 PE = 1 SV = 3

SWISS-PROT: P02535-1 Tax_Id = 10090
58
kDa
7
39
7
0

Gene_Symbol = Krt10 Isoform 1 of Keratin, type I

cytoskeletal 10

SWISS-PROT: P08730-1 Tax_Id = 10090
48
kDa
7
451
17
31

Gene_Symbol = Krt13 Isoform 1 of Keratin, type I

cytoskeletal 13

SWISS-PROT: Q6IFZ6 Tax_Id = 10090
61
kDa
7
32
10
5

Gene_Symbol = Krt77 Keratin, type II cytoskeletal 1b

Talin-2 OS = Homo sapiens OX = 9606 GN = TLN2 PE = 1
272
kDa
7
0
0
1

SV = 4

Transcription intermediary factor 1-beta OS = Homo
89
kDa
7
5
0
0

sapiens OX = 9606 GN = TRIM28 PE = 1 SV = 5

TREMBL: Q9TRI1 (Bos taurus) similar to inter-alpha-
106
kDa
7
57
7
8

trypsin inhibitor heavy chain2

U5 small nuclear ribonucleoprotein 200 kDa helicase
245
kDa
7
1
0
0

OS = Homo sapiens OX = 9606 GN = SNRNP200 PE = 1

SV = 2

Valine--tRNA ligase OS = Homo sapiens OX = 9606
140
kDa
7
8
0
4

GN = VARS PE = 1 SV = 4

26S proteasome regulatory subunit 4 OS = Homo sapiens
49
kDa
6
25
1
6

OX = 9606 GN = PSMC1 PE = 1 SV = 1

40S ribosomal protein S26 OS = Homo sapiens OX = 9606
13
kDa
6
0
6
6

GN = RPS26 PE = 1 SV = 3

60S ribosomal protein L24 OS = Homo sapiens OX = 9606
18
kDa
6
0
5
6

GN = RPL24 PE = 1 SV = 1

60S ribosomal protein L27a OS = Homo sapiens
17
kDa
6
0
6
4

OX = 9606 GN = RPL27A PE = 1 SV = 2

Alpha-centractin OS = Homo sapiens OX = 9606
43
kDa
6
26
3
11

GN = ACTR1A PE = 1 SV = 1

ATP-dependent RNA helicase DDX18 OS = Homo
75
kDa
6
5
3
8

sapiens OX = 9606 GN = DDX18 PE = 1 SV = 2

Collagen alpha-1(IV) chain OS = Homo sapiens OX = 9606
161
kDa
6
69
21
7

GN = COL4A1 PE = 1 SV = 4

Collagen alpha-1(VIII) chain OS = Homo sapiens
73
kDa
6
0
29
22

OX = 9606 GN = COL8A1 PE = 1 SV = 2

Cullin-associated NEDD8-dissociated protein 1
136
kDa
6
0
0
3

OS = Homo sapiens GN = CAND1 PE = 1 SV = 2

Dihydrolipoyllysine-residue succinyltransferase
49
kDa
6
17
0
8

component of 2-oxoglutarate dehydrogenase complex,

mitochondrial OS = Homo sapiens OX = 9606 GN = DLST

PE = 1 SV = 4

Dihydropyrimidinase-related protein 2 OS = Homo
62
kDa
6
3
0
5

sapiens OX = 9606 GN = DPYSL2 PE = 1 SV = 1

Eukaryotic translation initiation factor 3 subunit M
43
kDa
6
11
0
5

OS = Homo sapiens OX = 9606 GN = EIF3M PE = 1 SV = 1

Exportin-1 OS = Homo sapiens OX = 9606 GN = XPO1
123
kDa
6
0
0
0

PE = 1 SV = 1

F-actin-capping protein subunit alpha-2 OS = Homo
33
kDa
6
33
8
9

sapiens OX = 9606 GN = CAPZA2 PE = 1 SV = 3

Glycogen phosphorylase, brain form OS = Homo sapiens
97
kDa
6
0
0
1

OX = 9606 GN = PYGB PE = 1 SV = 5

Importin-7 OS = Homo sapiens OX = 9606 GN = IPO7
120
kDa
6
0
0
0

PE = 1 SV = 1

Isoform 2 of 6-phosphogluconate dehydrogenase,
52
kDa
6
4
0
3

decarboxylating OS = Homo sapiens OX = 9606 GN = PGD

Isoform 2 of Coatomer subunit beta′ OS = Homo sapiens
99
kDa
6
10
0
4

OX = 9606 GN = COPB2

Isoform 2 of Coronin-1C OS = Homo sapiens OX = 9606
54
kDa
6
36
5
7

GN = CORO1C

Isoform 2 of Elongation factor 1-delta OS = Homo sapiens
71
kDa
6
32
3
4

OX = 9606 GN = EEF1D

Isoform 2 of Inverted formin-2 OS = Homo sapiens
135
kDa
6
4
0
1

OX = 9606 GN = INF2

Isoform 2 of Programmed cell death 6-interacting protein
97
kDa
6
3
0
4

OS = Homo sapiens OX = 9606 GN = PDCD6IP

Isoform 2 of Surfeit locus protein 4 OS = Homo sapiens
18
kDa
6
10
3
7

OX = 9606 GN = SURF4

Isoform 3 of Plasminogen activator inhibitor 1 RNA-
43
kDa
6
11
6
7

binding protein OS = Homo sapiens OX = 9606

GN = SERBP1

Isoform 5 of Phosphatidylinositol-binding clathrin
70
kDa
6
5
0
7

assembly protein OS = Homo sapiens GN = PICALM

Junction plakoglobin OS = Homo sapiens OX = 9606
82
kDa
6
38
0
6

GN = JUP PE = 1 SV = 3

Lamina-associated polypeptide 2, isoforms beta/gamma
51
kDa
6
26
7
7

OS = Homo sapiens OX = 9606 GN = TMPO PE = 1 SV = 2

Leucine-rich repeat-containing protein 59 OS = Homo
35
kDa
6
0
7
10

sapiens OX = 9606 GN = LRRC59 PE = 1 SV = 1

Multifunctional protein ADE2 OS = Homo sapiens
47
kDa
6
3
0
2

OX = 9606 GN = PAICS PE = 1 SV = 3

Nicotinamide N-methyltransferase OS = Homo sapiens
30
kDa
6
0
0
1

OX = 9606 GN = NNMT PE = 1 SV = 1

Poly [ADP-ribose] polymerase 4 OS = Homo sapiens
193
kDa
6
19
0
5

OX = 9606 GN = PARP4 PE = 1 SV = 3

Protein S100-A6 OS = Homo sapiens OX = 9606
10
kDa
6
0
1
4

GN = S100A6 PE = 1 SV = 1

RuvB-like 2 OS = Homo sapiens OX = 9606 GN = RUVBL2
51
kDa
6
19
0
5

PE = 1 SV = 3

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
115
kDa
6
6
0
0

OS = Homo sapiens GN = ATP2A2 PE = 1 SV = 1

Signal transducer and activator of transcription 1-
87
kDa
6
15
1
5

alpha/beta OS = Homo sapiens OX = 9606 GN = STAT1

PE = 1 SV = 2

Synaptic vesicle membrane protein VAT-1 homolog
42
kDa
6
6
0
7

OS = Homo sapiens OX = 9606 GN = VAT1 PE = 1 SV = 2

Ubiquitin carboxyl-terminal hydrolase OS = Homo sapiens
27
kDa
6
0
0
4

OX = 9606 GN = UCHL1 PE = 1 SV = 1

Very-long-chain 3-oxoacyl-CoA reductase OS = Homo
34
kDa
6
0
2
6

sapiens OX = 9606 GN = HSD17B12 PE = 1 SV = 2

26S proteasome non-ATPase regulatory subunit 13
43
kDa
5
9
0
4

OS = Homo sapiens OX = 9606 GN = PSMD13 PE = 1 SV = 2

26S proteasome regulatory subunit 10B OS = Homo
44
kDa
5
0
0
5

sapiens OX = 9606 GN = PSMC6 PE = 1 SV = 1

40S ribosomal protein S10 OS = Homo sapiens OX = 9606
19
kDa
5
38
13
12

GN = RPS10 PE = 1 SV = 1

40S ribosomal protein S11 OS = Homo sapiens OX = 9606
18
kDa
5
26
3
7

GN = RPS11 PE = 1 SV = 3

60S ribosomal protein L21 OS = Homo sapiens OX = 9606
19
kDa
5
34
8
7

GN = RPL21 PE = 1 SV = 2

60S ribosomal protein L22 OS = Homo sapiens OX = 9606
15
kDa
5
0
6
8

GN = RPL22 PE = 1 SV = 2

60S ribosomal protein L23a (Fragment) OS = Homo
19
kDa
5
0
9
9

sapiens OX = 9606 GN = RPL23A PE = 1 SV = 1

60S ribosomal protein L27 OS = Homo sapiens OX = 9606
16
kDa
5
0
6
11

GN = RPL27 PE = 1 SV = 2

60S ribosomal protein L28 OS = Homo sapiens OX = 9606
16
kDa
5
13
4
4

GN = RPL28 PE = 1 SV = 3

60S ribosomal protein L31 OS = Homo sapiens OX = 9606
14
kDa
5
33
8
6

GN = RPL31 PE = 1 SV = 1

60S ribosomal protein L36 OS = Homo sapiens OX = 9606
12
kDa
5
0
7
7

GN = RPL36 PE = 1 SV = 3

Actin-related protein 2/3 complex subunit 3 OS = Homo
21
kDa
5
0
4
7

sapiens OX = 9606 GN = ARPC3 PE = 1 SV = 3

Actin-related protein 2/3 complex subunit 4 OS = Homo
20
kDa
5
19
2
6

sapiens OX = 9606 GN = ARPC4 PE = 1 SV = 3

Calpain-1 catalytic subunit OS = Homo sapiens OX = 9606
82
kDa
5
27
0
6

GN = CAPN1 PE = 1 SV = 1

Calponin-2 OS = Homo sapiens OX = 9606 GN = CNN2
34
kDa
5
5
1
6

PE = 1 SV = 4

Cathepsin D OS = Homo sapiens OX = 9606 GN = CTSD
45
kDa
5
0
0
3

PE = 1 SV = 1

Cleavage and polyadenylation specificity factor subunit 5
26
kDa
5
0
0
6

OS = Homo sapiens OX = 9606 GN = NUDT21 PE = 1 SV = 1

Coatomer subunit epsilon OS = Homo sapiens GN = COPE
34
kDa
5
14
2
8

PE = 1 SV = 3

Copine-3 OS = Homo sapiens OX = 9606 GN = CPNE3
60
kDa
5
0
0
1

PE = 1 SV = 1

Cytochrome c oxidase subunit 2 OS = Homo sapiens
26
kDa
5
0
0
6

OX = 9606 GN = MT-CO2 PE = 1 SV = 1

DNA-(apurinic or apyrimidinic site) lyase OS = Homo
36
kDa
5
8
0
3

sapiens OX = 9606 GN = APEX1 PE = 1 SV = 2

Erlin-1 OS = Homo sapiens OX = 9606 GN = ERLIN1 PE = 1
39
kDa
5
0
0
4

SV = 1

Eukaryotic translation elongation factor 1 epsilon-1
20
kDa
5
7
2
7

OS = Homo sapiens GN = EEF1E1 PE = 1 SV = 1

Eukaryotic translation initiation factor 2 subunit 1
36
kDa
5
9
1
7

OS = Homo sapiens OX = 9606 GN = EIF2S1 PE = 1 SV = 3

Eukaryotic translation initiation factor 3 subunit H
42
kDa
5
0
0
3

OS = Homo sapiens OX = 9606 GN = EIF3H PE = 1 SV = 1

Heat shock 70 kDa protein 4 OS = Homo sapiens
94
kDa
5
4
0
1

OX = 9606 GN = HSPA4 PE = 1 SV = 4

High mobility group protein B1 OS = Homo sapiens
25
kDa
5
0
0
3

OX = 9606 GN = HMGB1 PE = 1 SV = 3

Importin-9 OS = Homo sapiens OX = 9606 GN = IPO9
116
kDa
5
0
0
4

PE = 1 SV = 3

Isoform 2 of 26S proteasome non-ATPase regulatory
102
kDa
5
10
0
3

subunit 1 OS = Homo sapiens OX = 9606 GN = PSMD1

Isoform 2 of Calcium-binding mitochondrial carrier
74
kDa
5
10
0
9

protein Aralar2 OS = Homo sapiens OX = 9606

GN = SLC25A13

Isoform 2 of Collagen alpha-3(VI) chain OS = Homo
321
kDa
5
0
1
1

sapiens OX = 9606 GN = COL6A3

Isoform 2 of Eukaryotic translation initiation factor 3
99
kDa
5
5
0
6

subunit B OS = Homo sapiens OX = 9606 GN = EIF3B

Isoform 2 of Glucose-6-phosphate isomerase OS = Homo
64
kDa
5
4
0
2

sapiens OX = 9606 GN = GPI

Isoform 2 of HLA class I histocompatibility antigen, A-
41
kDa
5
3
0
3

11 alpha chain OS = Homo sapiens OX = 9606 GN = HLA-

A

Isoform 2 of Myb-binding protein 1A OS = Homo sapiens
149
kDa
5
1
0
0

OX = 9606 GN = MYBBP1A

Isoform 2 of Serine/arginine-rich splicing factor 2
24
kDa
5
2
0
2

OS = Homo sapiens OX = 9606 GN = SRSF2

Isoform 2 of U1 small nuclear ribonucleoprotein 70 kDa
51
kDa
5
0
0
5

OS = Homo sapiens OX = 9606 GN = SNRNP70

Isoform 3 of Glutaminase kidney isoform, mitochondrial
65
kDa
5
7
0
3

OS = Homo sapiens OX = 9606 GN = GLS

Isoform 4 of AP-3 complex subunit delta-1 OS = Homo
115
kDa
5
5
0
2

sapiens GN = AP3D1

Isoform 4 of Protein phosphatase 1 regulatory subunit
109
kDa
5
10
3
7

12A OS = Homo sapiens OX = 9606 GN = PPP1R12A

Isoform Short of Eukaryotic translation initiation factor
25
kDa
5
5
1
4

4H OS = Homo sapiens OX = 9606 GN = EIF4H

Lon protease homolog, mitochondrial OS = Homo sapiens
106
kDa
5
0
0
6

GN = LONP1 PE = 1 SV = 2

Mannosyl-oligosaccharide glucosidase OS = Homo
92
kDa
5
22
4
11

sapiens GN = MOGS PE = 1 SV = 5

Prolyl 3-hydroxylase 1 OS = Homo sapiens OX = 9606
83
kDa
5
6
0
3

GN = P3H1 PE = 1 SV = 2

Proteasome subunit alpha type-4 OS = Homo sapiens
29
kDa
5
0
0
7

OX = 9606 GN = PSMA4 PE = 1 SV = 1

Protein LYRIC OS = Homo sapiens OX = 9606
64
kDa
5
10
6
9

GN = MTDH PE = 1 SV = 2

Protein/nucleic acid deglycase DJ-1 OS = Homo sapiens
20
kDa
5
0
0
3

OX = 9606 GN = PARK7 PE = 1 SV = 2

Ras-related protein Rab-1A OS = Homo sapiens OX = 9606
23
kDa
5
13
2
8

GN = RAB1A PE = 1 SV = 3

Ras-related protein Rab-3B OS = Homo sapiens OX = 9606
25
kDa
5
0
2
7

GN = RAB3B PE = 1 SV = 2

Rho GDP-dissociation inhibitor 1 OS = Homo sapiens
23
kDa
5
0
0
4

OX = 9606 GN = ARHGDIA PE = 1 SV = 3

Signal recognition particle subunit SRP72 OS = Homo
75
kDa
5
8
1
8

sapiens OX = 9606 GN = SRP72 PE = 1 SV = 3

Small nuclear ribonucleoprotein Sm D2 OS = Homo
14
kDa
5
11
0
5

sapiens OX = 9606 GN = SNRPD2 PE = 1 SV = 1

Sorting and assembly machinery component 50 homolog
52
kDa
5
19
4
12

OS = Homo sapiens OX = 9606 GN = SAMM50 PE = 1 SV = 3

Src substrate cortactin OS = Homo sapiens OX = 9606
62
kDa
5
38
12
8

GN = CTTN PE = 1 SV = 2

SWI/SNF complex subunit SMARCC1 OS = Homo
123
kDa
5
0
0
2

sapiens OX = 9606 GN = SMARCC1 PE = 1 SV = 3

Transcription factor BTF3 OS = Homo sapiens OX = 9606
22
kDa
5
8
0
7

GN = BTF3 PE = 1 SV = 1

Translocon-associated protein subunit delta OS = Homo
19
kDa
5
0
2
4

sapiens OX = 9606 GN = SSR4 PE = 1 SV = 1

TREMBL: Q1RMK2 (Bos taurus) IGHM protein
65
kDa
5
0
0
0

WD repeat-containing protein 1 OS = Homo sapiens
66
kDa
5
11
0
5

OX = 9606 GN = WDR1 PE = 1 SV = 4

Zyxin OS = Homo sapiens OX = 9606 GN = ZYX PE = 1
61
kDa
5
13
0
4

SV = 1

2-oxoglutarate dehydrogenase, mitochondrial OS = Homo
116
kDa
4
2
0
6

sapiens OX = 9606 GN = OGDH PE = 1 SV = 3

40S ribosomal protein S27-like OS = Homo sapiens
9
kDa
4
0
1
1

OX = 9606 GN = RPS27L PE = 1 SV = 3

Adenosylhomocysteinase OS = Homo sapiens OX = 9606
48
kDa
4
4
0
2

GN = AHCY PE = 1 SV = 4

ADP-ribosylation factor 6 OS = Homo sapiens OX = 9606
20
kDa
4
0
0
2

GN = ARF6 PE = 1 SV = 2

Alanine--tRNA ligase, cytoplasmic OS = Homo sapiens
107
kDa
4
0
0
2

OX = 9606 GN = AARS PE = 1 SV = 2

ATPase family AAA domain-containing protein 3A
71
kDa
4
22
5
9

OS = Homo sapiens OX = 9606 GN = ATAD3A PE = 1 SV = 2

Coatomer subunit delta OS = Homo sapiens OX = 9606
57
kDa
4
10
0
5

GN = ARCN1 PE = 1 SV = 1

Cold-inducible RNA-binding protein OS = Homo sapiens
19
kDa
4
3
0
4

GN = CIRBP PE = 1 SV = 1

Copine-1 OS = Homo sapiens OX = 9606 GN = CPNE1
59
kDa
4
0
0
2

PE = 1 SV = 1

Cytochrome b-c1 complex subunit 2, mitochondrial
48
kDa
4
0
0
8

OS = Homo sapiens OX = 9606 GN = UQCRC2 PE = 1 SV = 3

DBH-like monooxygenase protein 1 OS = Homo sapiens
70
kDa
4
17
5
4

OX = 9606 GN = MOXD1 PE = 1 SV = 1

EH domain-containing protein 1 OS = Homo sapiens
61
kDa
4
11
0
9

OX = 9606 GN = EHD1 PE = 1 SV = 2

Eukaryotic translation initiation factor 3 subunit C
105
kDa
4
4
0
5

OS = Homo sapiens OX = 9606 GN = EIF3C PE = 1 SV = 1

Eukaryotic translation initiation factor 4 gamma 2
102
kDa
4
8
1
3

OS = Homo sapiens GN = EIF4G2 PE = 1 SV = 1

Eukaryotic translation initiation factor 6 OS = Homo
27
kDa
4
10
2
5

sapiens OX = 9606 GN = EIF6 PE = 1 SV = 1

Guanine nucleotide-binding protein G(I)/G(S)/G(T)
37
kDa
4
12
3
4

subunit beta-1 OS = Homo sapiens OX = 9606 GN = GNB1

PE = 1 SV = 3

Isoform 10 of Calpastatin OS = Homo sapiens OX = 9606
82
kDa
4
4
0
1

GN = CAST

Isoform 2 of 40S ribosomal protein S24 OS = Homo
15
kDa
4
46
10
8

sapiens OX = 9606 GN = RPS24

Isoform 2 of Chromodomain-helicase-DNA-binding
221
kDa
4
5
0
1

protein 4 OS = Homo sapiens GN = CHD4

Isoform 2 of Eukaryotic translation initiation factor 3
61
kDa
4
5
0
6

subunit L OS = Homo sapiens OX = 9606 GN = EIF3L

Isoform 2 of Glucosidase 2 subunit beta OS = Homo
59
kDa
4
5
0
4

sapiens OX = 9606 GN = PRKCSH

Isoform 2 of Hexokinase-1 OS = Homo sapiens OX = 9606
102
kDa
4
3
0
1

GN = HK1

Isoform 2 of Isocitrate dehydrogenase [NADP],
45
kDa
4
19
1
4

mitochondrial OS = Homo sapiens OX = 9606 GN = IDH2

Isoform 2 of Nodal modulator 2 OS = Homo sapiens
134
kDa
4
4
0
3

OX = 9606 GN = NOMO2

Isoform 2 of Plastin-3 OS = Homo sapiens OX = 9606
69
kDa
4
0
0
1

GN = PLS3

Isoform 2 of Proteasome subunit alpha type-3 OS = Homo
28
kDa
4
6
0
4

sapiens OX = 9606 GN = PSMA3

Isoform 2 of Protein SET OS = Homo sapiens GN = SET
32
kDa
4
7
0
4

Isoform 2 of Splicing factor U2AF 65 kDa subunit
53
kDa
4
1
0
5

OS = Homo sapiens OX = 9606 GN = U2AF2

Isoform 2 of SWI/SNF complex subunit SMARCC2
125
kDa
4
9
0
3

OS = Homo sapiens OX = 9606 GN = SMARCC2

Isoform 2 of Unconventional myosin-Ib OS = Homo
125
kDa
4
16
0
0

sapiens OX = 9606 GN = MYO1B

Isoform 3 of Dynactin subunit 1 OS = Homo sapiens
137
kDa
4
8
0
2

OX = 9606 GN = DCTN1

Isoform 3 of Heterogeneous nuclear ribonucleoprotein
31
kDa
4
10
2
6

A/B OS = Homo sapiens GN = HNRNPAB

Isoform 3 of Myoferlin OS = Homo sapiens OX = 9606
233
kDa
4
6
0
1

GN = MYOF

Isoform 3 of Nucleolar and coiled-body phosphoprotein 1
74
kDa
4
7
1
3

OS = Homo sapiens OX = 9606 GN = NOLC1

Isoform 4 of Inhibitor of nuclear factor kappa-B kinase-
43
kDa
4
11
2
5

interacting protein OS = Homo sapiens OX = 9606

GN = IKBIP

Isoform 6 of MMS19 nucleotide excision repair protein
108
kDa
4
0
0
1

homolog OS = Homo sapiens GN = MMS19

Isoform Short of RNA-binding protein FUS OS = Homo
53
kDa
4
9
0
4

sapiens OX = 9606 GN = FUS

Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5
838
kDa
4
2
0
0

OS = Homo sapiens OX = 9606 GN = MACF1 PE = 1 SV = 4

Mitochondrial carrier homolog 1 (Fragment) OS = Homo
43
kDa
4
0
0
5

sapiens OX = 9606 GN = MTCH1 PE = 1 SV = 1

Nuclease-sensitive element-binding protein 1 OS = Homo
36
kDa
4
0
7
9

sapiens OX = 9606 GN = YBX1 PE = 1 SV = 3

Nucleolar GTP-binding protein 1 OS = Homo sapiens
74
kDa
4
5
0
1

OX = 9606 GN = GTPBP4 PE = 1 SV = 3

OCIA domain-containing protein 2 OS = Homo sapiens
17
kDa
4
0
0
0

OX = 9606 GN = OCIAD2 PE = 1 SV = 1

Peroxisomal multifunctional enzyme type 2 OS = Homo
80
kDa
4
10
0
9

sapiens GN = HSD17B4 PE = 1 SV = 3

Probable ATP-dependent RNA helicase DDX6
54
kDa
4
4
0
2

OS = Homo sapiens OX = 9606 GN = DDX6 PE = 1 SV = 2

Proteasome subunit alpha type-2 OS = Homo sapiens
26
kDa
4
0
0
8

OX = 9606 GN = PSMA2 PE = 1 SV = 2

Proteasome subunit beta type-1 OS = Homo sapiens
26
kDa
4
0
0
6

OX = 9606 GN = PSMB1 PE = 1 SV = 2

Proteasome subunit beta type-3 OS = Homo sapiens
23
kDa
4
0
0
6

OX = 9606 GN = PSMB3 PE = 1 SV = 2

Proteasome subunit beta type-7 OS = Homo sapiens
30
kDa
4
0
0
6

OX = 9606 GN = PSMB7 PE = 1 SV = 1

Protein arginine N-methyltransferase 1 OS = Homo
42
kDa
4
3
0
1

sapiens GN = PRMT1 PE = 1 SV = 2

Ras GTPase-activating protein-binding protein 2
54
kDa
4
14
2
5

OS = Homo sapiens OX = 9606 GN = G3BP2 PE = 1 SV = 2

Ras suppressor protein 1 OS = Homo sapiens OX = 9606
32
kDa
4
16
1
8

GN = RSU1 PE = 1 SV = 3

RNA-binding protein Raly OS = Homo sapiens OX = 9606
32
kDa
4
14
2
7

GN = RALY PE = 1 SV = 1

Sideroflexin-1 OS = Homo sapiens OX = 9606GN = SFXN1
36
kDa
4
3
1
4

PE = 1 SV = 4

Sideroflexin-3 OS = Homo sapiens OX = 9606GN = SFXN3
36
kDa
4
0
0
4

PE = 1 SV = 3

Signal recognition particle 9 kDa protein OS = Homo
10
kDa
4
7
1
3

sapiens OX = 9606 GN = SRP9 PE = 1 SV = 2

Splicing factor 3A subunit 1 OS = Homo sapiens
89
kDa
4
6
0
5

OX = 9606 GN = SF3A1 PE = 1 SV = 1

SWISS-PROT: Q9TTE1 (Bos taurus) Endopin-1
46
kDa
4
4
2
1

precursor

Thy-l membrane glycoprotein OS = Homo sapiens
18
kDa
4
0
6
3

OX = 9606 GN = THY1 PE = 1 SV = 2

Transmembrane protein 43 OS = Homo sapiens OX = 9606
45
kDa
4
0
5
6

GN = TMEM43 PE = 1 SV = 1

TREMBL: Q1A7A4 (Bos taurus) similar to complement
189
kDa
4
0
0
0

component C5

Tricarboxylate transport protein, mitochondrial
34
kDa
4
2
0
3

OS = Homo sapiens OX = 9606 GN = SLC25A1 PE = 1 SV = 2

U2 small nuclear ribonucleoprotein A′ OS = Homo sapiens
28
kDa
4
0
0
4

OX = 9606 GN = SNRPA1 PE = 1 SV = 2

Vasodilator-stimulated phosphoprotein OS = Homo
40
kDa
4
10
0
10

sapiens OX = 9606 GN = VASP PE = 1 SV = 3

(Bos taurus) 47 kDa protein
47
kDa
3
0
0
0

(Bos taurus) similar to Complement C4-A precursor
193
kDa
3
7
4
4

26S proteasome non-ATPase regulatory subunit 5
56
kDa
3
4
0
1

OS = Homo sapiens OX = 9606 GN = PSMD5 PE = 1 SV = 3

26S proteasome non-ATPase regulatory subunit 7
37
kDa
3
10
0
6

OS = Homo sapiens OX = 9606 GN = PSMD7 PE = 1 SV = 2

26S proteasome regulatory subunit 7 OS = Homo sapiens
49
kDa
3
4
0
4

OX = 9606 GN = PSMC2 PE = 1 SV = 3

39S ribosomal protein L28, mitochondrial OS = Homo
30
kDa
3
0
0
1

sapiens OX = 9606 GN = MRPL28 PE = 1 SV = 4

40S ribosomal protein S15a OS = Homo sapiens OX = 9606
15
kDa
3
0
2
3

GN = RPS15A PE = 1 SV = 2

60S ribosomal protein L15 OS = Homo sapiens OX = 9606
24
kDa
3
27
3
11

GN = RPL15 PE = 1 SV = 2

Acetyl-CoA acetyltransferase, mitochondrial OS = Homo
45
kDa
3
11
0
5

sapiens OX = 9606 GN = ACAT1 PE = 1 SV = 1

ATP synthase F(0) complex subunit B1, mitochondrial
29
kDa
3
0
0
2

OS = Homo sapiens OX = 9606 GN = ATP5PB PE = 1 SV = 2

ATP-binding cassette sub-family D member 3 OS = Homo
75
kDa
3
8
2
2

sapiens OX = 9606 GN = ABCD3 PE = 1 SV = 1

Calponin-3 OS = Homo sapiens OX = 9606 GN = CNN3
36
kDa
3
4
1
6

PE = 1 SV = 1

Cell surface glycoprotein MUC18 OS = Homo sapiens
72
kDa
3
3
0
6

OX = 9606 GN = MCAM PE = 1 SV = 2

CTP synthase 1 OS = Homo sapiens OX = 9606
67
kDa
3
0
0
0

GN = CTPS1 PE = 1 SV = 2

Cytoplasmic dynein 1 light intermediate chain 1
57
kDa
3
11
0
4

OS = Homo sapiens OX = 9606 GN = DYNC1LI1 PE = 1

SV = 3

Cytoplasmic FMR1-interacting protein 1 OS = Homo
145
kDa
3
2
0
0

sapiens OX = 9606 GN = CYFIP1 PE = 1 SV = 1

Desmoglein-2 OS = Homo sapiens OX = 9606 GN = DSG2
122
kDa
3
17
5
7

PE = 1 SV = 2

Desmoplakin OS = Homo sapiens OX = 9606 GN = DSP
332
kDa
3
35
0
0

PE = 1 SV = 3

Dihydrolipoyllysine-residue acetyltransferase component
69
kDa
3
0
2
10

of pyruvate dehydrogenase complex, mitochondrial

OS = Homo sapiens OX = 9606 GN = DLAT PE = 1 SV = 3

DnaJ homolog subfamily A member 2 OS = Homo sapiens
46
kDa
3
0
1
6

OX = 9606 GN = DNAJA2 PE = 1 SV = 1

Dynein light chain Tctex-type 1 OS = Homo sapiens
12
kDa
3
13
3
5

OX = 9606 GN = DYNLT1 PE = 1 SV = 1

E3 ubiquitin/ISG15 ligase TRIM25 OS = Homo sapiens
71
kDa
3
0
0
1

OX = 9606 GN = TRIM25 PE = 1 SV = 2

EGF-like repeat and discoidin I-like domain-containing
54
kDa
3
26
1
7

protein 3 OS = Homo sapiens OX = 9606 GN = EDIL3 PE = 1

SV = 1

Enoyl-CoA hydratase, mitochondrial OS = Homo sapiens
31
kDa
3
0
0
2

OX = 9606 GN = ECHS1 PE = 1 SV = 4

Epidermal growth factor receptor kinase substrate 8-like
81
kDa
3
4
0
5

protein 2 OS = Homo sapiens OX = 9606 GN = EPS8L2

PE = 1 SV = 2

ER lumen protein-retaining receptor 1 OS = Homo sapiens
25
kDa
3
0
2
1

OX = 9606 GN = KDELR1 PE = 1 SV = 1

Eukaryotic translation initiation factor 2 subunit 2
38
kDa
3
0
7
10

OS = Homo sapiens OX = 9606 GN = EIF2S2 PE = 1 SV = 2

General transcription factor II-I OS = Homo sapiens
112
kDa
3
27
3
3

OX = 9606 GN = GTF2I PE = 1 SV = 2

High mobility group protein HMGI-C OS = Homo sapiens
12
kDa
3
48
3
0

GN = HMGA2 PE = 1 SV = 1

Inosine-5′-monophosphate dehydrogenase 2 OS = Homo
56
kDa
3
0
0
2

sapiens OX = 9606 GN = IMPDH2 PE = 1 SV = 2

Isoform 1 of Apoptosis inhibitor 5 OS = Homo sapiens
49
kDa
3
5
0
3

OX = 9606 GN = API5

Isoform 12 of Titin OS = Homo sapiens OX = 9606
3994
kDa
3
1
3
3

GN = TTN

Isoform 2 of 3-hydroxyacyl-CoA dehydrogenase type-2
26
kDa
3
2
0
1

OS = Homo sapiens OX = 9606 GN = HSD17B10

Isoform 2 of ATP-dependent RNA helicase DDX54
99
kDa
3
1
0
3

OS = Homo sapiens OX = 9606 GN = DDX54

Isoform 2 of B-cell receptor-associated protein 31
35
kDa
3
1
4
7

OS = Homo sapiens OX = 9606 GN = BCAP31

Isoform 2 of Calcium-binding mitochondrial carrier
51
kDa
3
1
0
5

protein SCaMC-1 OS = Homo sapiens OX = 9606

GN = SLC25A24

Isoform 2 of Collagen alpha-1(V) chain OS = Homo
184
kDa
3
0
13
6

sapiens OX = 9606 GN = COL5A1

Isoform 2 of E3 ubiquitin-protein ligase UBR4
576
kDa
3
0
0
1

OS = Homo sapiens OX = 9606 GN = UBR4

Isoform 2 of Importin-4 OS = Homo sapiens GN = IPO4
119
kDa
3
0
0
0

Isoform 2 of Insulin-like growth factor 2 mRNA-binding
62
kDa
3
19
2
5

protein 2 OS = Homo sapiens GN = IGF2BP2

Isoform 2 of NADH dehydrogenase [ubiquinone] 1 alpha
49
kDa
3
0
0
2

subcomplex subunit 10, mitochondrial OS = Homo sapiens

OX = 9606 GN = NDUFA10

Isoform 2 of NADH-cytochrome b5 reductase 3
32
kDa
3
6
0
3

OS = Homo sapiens OX = 9606 GN = CYB5R3

Isoform 2 of Nuclear pore complex protein Nup107
103
kDa
3
1
0
0

OS = Homo sapiens OX = 9606 GN = NUP107

Isoform 2 of Protein Dok-7 OS = Homo sapiens OX = 9606
37
kDa
3
0
2
5

GN = DOK7

Isoform 2 of Protein FAM98B OS = Homo sapiens
46
kDa
3
9
0
4

OX = 9606 GN = FAM98B

Isoform 2 of Sacsin OS = Homo sapiens OX = 9606
437
kDa
3
0
0
0

GN = SACS

Isoform 2 of Serine/arginine-rich splicing factor 3
14
kDa
3
8
0
4

OS = Homo sapiens OX = 9606 GN = SRSF3

Isoform 2 of Small nuclear ribonucleoprotein Sm D3
13
kDa
3
10
2
3

OS = Homo sapiens OX = 9606 GN = SNRPD3

Isoform 2 of Stathmin OS = Homo sapiens OX = 9606
20
kDa
3
0
0
3

GN = STMN1

Isoform 2 of TP53-binding protein 1 OS = Homo sapiens
214
kDa
3
4
0
0

OX = 9606 GN = TP53BP1

Isoform 2 of Very long-chain specific acyl-CoA
68
kDa
3
10
0
5

dehydrogenase, mitochondrial OS = Homo sapiens

OX = 9606 GN = ACADVL

Isoform 2 of Voltage-dependent anion-selective channel
31
kDa
3
15
0
5

protein 3 OS = Homo sapiens OX = 9606 GN = VDAC3

Isoform 2 of V-type proton ATPase catalytic subunit A
65
kDa
3
15
1
2

OS = Homo sapiens OX = 9606 GN = ATP6V1A

Isoform 3 of 4F2 cell-surface antigen heavy chain
62
kDa
3
1
1
1

OS = Homo sapiens GN = SLC3A2

Isoform 3 of Aldehyde dehydrogenase family 16 member
80
kDa
3
0
0
1

A1 OS = Homo sapiens OX = 9606 GN = ALDH16A1

Isoform 3 of Drebrin OS = Homo sapiens GN = DBN1
76
kDa
3
31
4
3

Isoform 3 of Erbin OS = Homo sapiens OX = 9606
153
kDa
3
0
0
0

GN = ERBIN

Isoform 3 of Nucleoside diphosphate kinase B OS = Homo
30
kDa
3
12
0
7

sapiens GN = NME2

Isoform 3 of Perilipin-3 OS = Homo sapiens OX = 9606
47
kDa
3
1
0
3

GN = PLIN3

Isoform 3 of SUN domain-containing protein 2
80
kDa
3
15
4
12

OS = Homo sapiens OX = 9606 GN = SUN2

Isoform 3 of Transportin-3 OS = Homo sapiens OX = 9606
103
kDa
3
0
0
0

GN = TNPO3

Isoform 4 of 26S proteasome non-ATPase regulatory
52
kDa
3
17
0
2

subunit 6 OS = Homo sapiens OX = 9606 GN = PSMD6

Isoform 9 of Protein transport protein Sec31A OS = Homo
131
kDa
3
3
0
1

sapiens GN = SEC31A

Isoform K of Kinesin light chain 1 OS = Homo sapiens
70
kDa
3
2
0
2

OX = 9606 GN = KLC1

MICOS complex subunit MIC19 OS = Homo sapiens
26
kDa
3
0
3
6

OX = 9606 GN = CHCHD3 PE = 1 SV = 1

Nuclear pore complex protein Nup205 OS = Homo
228
kDa
3
0
0
0

sapiens OX = 9606 GN = NUP205 PE = 1 SV = 3

Nuclear pore complex protein Nup93 OS = Homo sapiens
93
kDa
3
6
0
3

OX = 9606 GN = NUP93 PE = 1 SV = 2

PC4 and SFRS1 -interacting protein OS = Homo sapiens
60
kDa
3
16
1
5

OX = 9606 GN = PSIP1 PE = 1 SV = 1

Peroxiredoxin-6 OS = Homo sapiens OX = 9606
25
kDa
3
0
0
0

GN = PRDX6 PE = 1 SV = 3

PRA1 family protein 3 OS = Homo sapiens OX = 9606
22
kDa
3
7
1
4

GN = ARL6IP5 PE = 1 SV = 1

Proliferating cell nuclear antigen OS = Homo sapiens
29
kDa
3
0
0
0

OX = 9606 GN = PCNA PE = 1 SV = 1

Proliferation-associated protein 2G4 OS = Homo sapiens
44
kDa
3
16
0
6

OX = 9606 GN = PA2G4 PE = 1 SV = 3

Proteasome adapter and scaffold protein ECM29
204
kDa
3
0
0
2

OS = Homo sapiens OX = 9606 GN = ECPAS PE = 1 SV = 2

Proteasome subunit beta type-4 OS = Homo sapiens
29
kDa
3
0
0
4

OX = 9606 GN = PSMB4 PE = 1 SV = 4

Proteasome subunit beta type-6 OS = Homo sapiens
25
kDa
3
0
0
3

OX = 9606 GN = PSMB6 PE = 1 SV = 4

Protein DEK OS = Homo sapiens OX = 9606 GN = DEK
43
kDa
3
2
0
2

PE = 1 SV = 1

Protein S 100-A11 OS = Homo sapiens OX = 9606
12
kDa
3
0
0
2

GN = S100A11 PE = 1 SV = 2

Protein transport protein Sec61 subunit beta OS = Homo
10
kDa
3
1
2
2

sapiens OX = 9606 GN = SEC61B PE = 1 SV = 2

Puromycin-sensitive aminopeptidase OS = Homo sapiens
103
kDa
3
0
0
2

GN = NPEPPS PE = 1 SV = 2

Ras-related protein Rab-11B OS = Homo sapiens
24
kDa
3
9
1
6

OX = 9606 GN = RAB11B PE = 1 SV = 4

Ras-related protein Rab-14 OS = Homo sapiens OX = 9606
24
kDa
3
0
0
6

GN = RAB14 PE = 1 SV = 4

Ras-related protein Rap-1b OS = Homo sapiens OX = 9606
21
kDa
3
7
2
3

GN = RAP1B PE = 1 SV = 1

Ras-related protein R-Ras OS = Homo sapiens OX = 9606
23
kDa
3
0
0
2

GN = RRAS PE = 1 SV = 1

RNA transcription, translation and transport factor
28
kDa
3
0
4
6

protein OS = Homo sapiens OX = 9606 GN = RTRAF PE = 1

SV = 1

SAP domain-containing ribonucleoprotein OS = Homo
24
kDa
3
0
0
2

sapiens OX = 9606 GN = SARNP PE = 1 SV = 3

SWISS-PROT: P06868 (Bos taurus) Plasminogen
91
kDa
3
1
5
0

precursor

SWISS-PROT: P41361 (Bos taurus) Antithrombin-III
52
kDa
3
3
0
0

precursor

TAR DNA-binding protein 43 OS = Homo sapiens
45
kDa
3
2
0
3

OX = 9606 GN = TARDBP PE = 1 SV = 1

Thioredoxin reductase 1, cytoplasmic OS = Homo sapiens
71
kDa
3
0
0
1

GN = TXNRD1 PE = 1 SV = 3

Thrombospondin type-1 domain-containing protein 4
112
kDa
3
22
10
1

OS = Homo sapiens OX = 9606 GN = THSD4 PE = 2 SV = 2

TREMBL: Q2KJF1 (Bos taurus) Alpha-1-Bglycoprotein
54
kDa
3
11
1
3

tRNA-splicing ligase RtcB homolog OS = Homo sapiens
55
kDa
3
19
3
9

OX = 9606 GN = RTCB PE = 1 SV = 1

Tyrosine--tRNA ligase, cytoplasmic OS = Homo sapiens
59
kDa
3
0
0
2

OX = 9606 GN = YARS PE = 1 SV = 4

Ubiquitin thioesterase OTUB1 OS = Homo sapiens
31
kDa
3
0
0
1

OX = 9606 GN = OTUB1 PE = 1 SV = 2

Vigilin OS = Homo sapiens OX = 9606 GN = HDLBP PE = 1
141
kDa
3
9
0
2

SV = 2

V-type proton ATPase 116 kDa subunit a isoform 3
93
kDa
3
16
1
2

OS = Homo sapiens OX = 9606 GN = TCIRG1 PE = 1 SV = 3

WD repeat-containing protein 61 OS = Homo sapiens
34
kDa
3
0
1
4

OX = 9606 GN = WDR61 PE = 1 SV = 1

39S ribosomal protein L41, mitochondrial OS = Homo
15
kDa
2
0
0
5

sapiens OX = 9606 GN = MRPL41 PE = 1 SV = 1

40S ribosomal protein S25 OS = Homo sapiens OX = 9606
14
kDa
2
0
8
7

GN = RPS25 PE = 1 SV = 1

60S acidic ribosomal protein P1 OS = Homo sapiens
12
kDa
2
13
3
5

OX = 9606 GN = RPLP1 PE = 1 SV = 1

Actin-like protein 6A OS = Homo sapiens OX = 9606
47
kDa
2
12
0
2

GN = ACTL6A PE = 1 SV = 1

Actin-related protein 2/3 complex subunit 5 OS = Homo
16
kDa
2
15
5
7

sapiens OX = 9606 GN = ARPC5 PE = 1 SV = 3

Actin-related protein 2/3 complex subunit 5-like protein
17
kDa
2
0
6
5

OS = Homo sapiens OX = 9606 GN = ARPC5L PE = 1 SV = 1

Activated RNA polymerase II transcriptional coactivator
14
kDa
2
1
0
2

p15 OS = Homo sapiens OX = 9606 GN = SUB1 PE = 1

SV = 3

Alcohol dehydrogenase [NADP(+)] OS = Homo sapiens
37
kDa
2
0
0
1

OX = 9606 GN = AKR1A1 PE = 1 SV = 3

Aspartyl/asparaginyl beta-hydroxylase OS = Homo
86
kDa
2
4
1
3

sapiens OX = 9606 GN = ASPH PE = 1 SV = 3

ATP synthase subunit f, mitochondrial OS = Homo
11
kDa
2
0
2
2

sapiens OX = 9606 GN = ATP5MF PE = 1 SV = 1

ATP-binding cassette sub-family B member 6,
78
kDa
2
0
0
0

mitochondrial (Fragment) OS = Homo sapiens OX = 9606

GN = ABCB6 PE = 1 SV = 1

Catenin delta-1 OS = Homo sapiens OX = 9606
108
kDa
2
13
0
1

GN = CTNND1 PE = 1 SV = 1

Cathepsin B OS = Homo sapiens OX = 9606 GN = CTSB
38
kDa
2
0
0
0

PE = 1 SV = 3

Caveolin-1 OS = Homo sapiens OX = 9606 GN = CAV1
20
kDa
2
11
2
4

PE = 1 SV = 4

Cell cycle and apoptosis regulator protein 2 OS = Homo
103
kDa
2
1
0
4

sapiens GN = CCAR2 PE = 1 SV = 2

Centromere protein V OS = Homo sapiens OX = 9606
30
kDa
2
3
0
1

GN = CENPV PE = 1 SV = 1

Citrate synthase OS = Homo sapiens OX = 9606 GN = CS
50
kDa
2
0
0
3

PE = 1 SV = 1

Cytochrome b-c1 complex subunit 1, mitochondrial
53
kDa
2
0
0
1

OS = Homo sapiens OX = 9606 GN = UQCRC1 PE = 1 SV = 3

Cytochrome c oxidase subunit 7A2, mitochondrial
9
kDa
2
0
0
1

OS = Homo sapiens OX = 9606 GN = COX7A2 PE = 1 SV = 1

Dystonin OS = Homo sapiens OX = 9606 GN = DST PE = 1
861
kDa
2
0
0
0

SV = 4

EH domain-containing protein 2 OS = Homo sapiens
61
kDa
2
2
0
3

OX = 9606 GN = EHD2 PE = 1 SV = 2

Enhancer of mRNA-decapping protein 4 OS = Homo
152
kDa
2
0
0
0

sapiens GN = EDC4 PE = 1 SV = 1

Eukaryotic translation initiation factor 5B OS = Homo
139
kDa
2
0
0
2

sapiens OX = 9606 GN = EIF5B PE = 1 SV = 4

Exosome RNA helicase MTR4 OS = Homo sapiens
118
kDa
2
0
0
1

OX = 9606 GN = MTREX PE = 1 SV = 3

Far upstream element-binding protein 2 OS = Homo
73
kDa
2
0
0
0

sapiens OX = 9606 GN = KHSRP PE = 1 SV = 4

Ferritin heavy chain OS = Homo sapiens OX = 9606
21
kDa
2
0
0
1

GN = FTH1 PE = 1 SV = 2

FH2 domain-containing protein 1 OS = Homo sapiens
125
kDa
2
0
0
0

OX = 9606 GN = FHDC1 PE = 1 SV = 2

Glutaredoxin-3 OS = Homo sapiens OX = 9606
37
kDa
2
0
0
0

GN = GLRX3 PE = 1 SV = 2

GTP-binding protein SAR1a OS = Homo sapiens
22
kDa
2
0
0
3

OX = 9606 GN = SAR1A PE = 1 SV = 1

Guanine nucleotide-binding protein G(I)/G(S)/G(T)
37
kDa
2
14
0
0

subunit beta-2 OS = Homo sapiens OX = 9606 GN = GNB2

PE = 1 SV = 3

Heterogeneous nuclear ribonucleoprotein U-like protein 2
85
kDa
2
8
0
2

OS = Homo sapiens OX = 9606 GN = HNRNPUL2 PE = 1

SV = 1

High mobility group protein B3 OS = Homo sapiens
23
kDa
2
0
0
3

OX = 9606 GN = HMGB3 PE = 1 SV = 4

Inversin OS = Homo sapiens OX = 9606 GN = INVS PE = 1
118
kDa
2
0
0
0

SV = 2

Isoform 10 of CD44 antigen OS = Homo sapiens
53
kDa
2
27
5
2

OX = 9606 GN = CD44

Isoform 2 of 40S ribosomal protein S20 OS = Homo
16
kDa
2
7
1
3

sapiens OX = 9606 GN = RPS20

Isoform 2 of AP-2 complex subunit alpha-2 OS = Homo
104
kDa
2
8
0
3

sapiens OX = 9606 GN = AP2A2

Isoform 2 of ATP-binding cassette sub-family F member
92
kDa
2
6
2
2

1 OS = Homo sapiens OX = 9606 GN = ABCF1

Isoform 2 of cAMP-dependent protein kinase type II-
43
kDa
2
11
0
3

alpha regulatory subunit OS = Homo sapiens OX = 9606

GN = PRKAR2A

Isoform 2 of Chromatin target of PRMT1 protein
27
kDa
2
4
2
2

OS = Homo sapiens OX = 9606 GN = CHTOP

Isoform 2 of Collagen alpha-1(XXII) chain OS = Homo
159
kDa
2
0
0
1

sapiens OX = 9606 GN = COL22A1

Isoform 2 of DNA repair protein RAD50 OS = Homo
155
kDa
2
0
0
1

sapiens OX = 9606 GN = RAD50

Isoform 2 of E3 ubiquitin-protein ligase RNF213
596
kDa
2
0
0
1

OS = Homo sapiens OX = 9606 GN = RNF213

Isoform 2 of Electron transfer flavoprotein subunit alpha,
30
kDa
2
1
0
5

mitochondrial OS = Homo sapiens OX = 9606 GN = ETFA

Isoform 2 of Enoyl-CoA delta isomerase 2, mitochondrial
40
kDa
2
0
0
0

OS = Homo sapiens OX = 9606 GN = ECI2

Isoform 2 of Eukaryotic peptide chain release factor
45
kDa
2
2
0
2

subunit 1 OS = Homo sapiens OX = 9606 GN = ETF1

Isoform 2 of Eukaryotic translation initiation factor 3
58
kDa
2
2
0
0

subunit D OS = Homo sapiens OX = 9606 GN = EIF3D

Isoform 2 of Fermitin family homolog 2 OS = Homo
72
kDa
2
0
0
6

sapiens OX = 9606 GN = FERMT2

Isoform 2 of Glutamine--fructose-6-phosphate
77
kDa
2
5
0
1

aminotransferase [isomerizing] 1 OS = Homo sapiens

OX = 9606 GN = GFPT1

Isoform 2 of Guanine nucleotide-binding protein-like 3
61
kDa
2
3
0
0

OS = Homo sapiens OX = 9606 GN = GNL3

Isoform 2 of Histidine--tRNA ligase, cytoplasmic
53
kDa
2
3
0
4

OS = Homo sapiens OX = 9606 GN = HARS

Isoform 2 of Histone H1.0 OS = Homo sapiens OX = 9606
19
kDa
2
1
3
3

GN = H1F0

Isoform 2 of Interferon-induced, double-stranded RNA-
57
kDa
2
1
0
1

activated protein kinase OS = Homo sapiens OX = 9606

GN = EIF2AK2

Isoform 2 of Neurotrimin OS = Homo sapiens OX = 9606
38
kDa
2
0
0
0

GN = NTM

Isoform 2 of Neutral cholesterol ester hydrolase 1
47
kDa
2
1
0
3

OS = Homo sapiens OX = 9606 GN = NCEH1

Isoform 2 of Nucleosome assembly protein 1-like 1
43
kDa
2
10
1
3

OS = Homo sapiens OX = 9606 GN = NAP1L1

Isoform 2 of Nucleosome assembly protein 1-like 4
44
kDa
2
0
0
3

OS = Homo sapiens OX = 9606 GN = NAP1L4

Isoform 2 of Polyadenylate-binding protein 2 OS = Homo
31
kDa
2
7
0
2

sapiens OX = 9606 GN = PABPN1

Isoform 2 of Pre-mRNA-splicing factor SYF2 OS = Homo
24
kDa
2
0
0
3

sapiens OX = 9606 GN = SYF2

Isoform 2 of Procollagen-lysine,2-oxoglutarate 5-
88
kDa
2
12
0
1

dioxygenase 1 OS = Homo sapiens OX = 9606 GN = PLOD1

Isoform 2 of Procollagen-lysine,2-oxoglutarate 5-
87
kDa
2
2
0
0

dioxygenase 2 OS = Homo sapiens OX = 9606 GN = PLOD2

Isoform 2 of Protein enabled homolog OS = Homo sapiens
64
kDa
2
26
1
18

OX = 9606 GN = ENAH

Isoform 2 of Protein SGT1 homolog OS = Homo sapiens
38
kDa
2
0
0
0

OX = 9606 GN = SUGT1

Isoform 2 of Protein transport protein Sec16A OS = Homo
229
kDa
2
0
0
1

sapiens OX = 9606 GN = SEC16A

Isoform 2 of RNA-binding protein with serine-rich
32
kDa
2
3
1
2

domain 1 OS = Homo sapiens OX = 9606 GN = RNPS1

Isoform 2 of Signal recognition particle subunit SRP68
67
kDa
2
9
0
0

OS = Homo sapiens OX = 9606 GN = SRP68

Isoform 2 of Syntenin-1 OS = Homo sapiens OX = 9606
32
kDa
2
6
0
0

GN = SDCBP

Isoform 2 of Translocating chain-associated membrane
40
kDa
2
6
4
5

protein 1 OS = Homo sapiens OX = 9606 GN = TRAM1

Isoform 2 of Trifunctional enzyme subunit beta,
49
kDa
2
51
9
10

mitochondrial OS = Homo sapiens OX = 9606

GN = HADHB

Isoform 2 of UDP-glucose: glycoprotein
175
kDa
2
2
0
1

glucosyltransferase 1 OS = Homo sapiens OX = 9606

GN = UGGT1

Isoform 3 of 28S ribosomal protein S29, mitochondrial
42
kDa
2
5
2
1

OS = Homo sapiens GN = DAP3

Isoform 3 of Basic leucine zipper and W2 domain-
51
kDa
2
1
0
4

containing protein 1 OS = Homo sapiens OX = 9606

GN = BZW1

Isoform 3 of E3 ubiquitin-protein ligase HUWE1
481
kDa
2
4
0
0

OS = Homo sapiens GN = HUWE1

Isoform 3 of Heterogeneous nuclear ribonucleoprotein
32
kDa
2
8
0
3

H3 OS = Homo sapiens GN = HNRNPH3

Isoform 3 of Integrin-linked protein kinase OS = Homo
36
kDa
2
0
0
2

sapiens OX = 9606 GN = ILK

Isoform 3 of Protein virilizer homolog OS = Homo sapiens
201
kDa
2
0
0
0

OX = 9606 GN = VIRMA

Isoform 3 of Ubiquitin-associated protein 2-like
113
kDa
2
7
0
7

OS = Homo sapiens OX = 9606 GN = UBAP2L

Isoform 4 of LIM domain and actin-binding protein 1
85
kDa
2
49
6
4

OS = Homo sapiens OX = 9606 GN = LIMA1

Isoform 4 of WASH complex subunit 2C OS = Homo
145
kDa
2
0
0
0

sapiens OX = 9606 GN = WASHC2C

Isoform Delta 10 of Calcium/calmodulin-dependent
56
kDa
2
5
0
0

protein kinase type II subunit delta OS = Homo sapiens

OX = 9606 GN = CAMK2D

Isoform LAMP-2B of Lysosome-associated membrane
45
kDa
2
0
0
2

glycoprotein 2 OS = Homo sapiens OX = 9606

GN = LAMP2

Leucine-rich repeat flightless-interacting protein 1
89
kDa
2
0
0
1

OS = Homo sapiens OX = 9606 GN = LRRFIP1 PE = 1 SV = 2

Lysophospholipid acyltransferase 7 OS = Homo sapiens
53
kDa
2
2
0
0

GN = MBOAT7 PE = 1 SV = 2

Microsomal glutathione S-transferase 3 OS = Homo
17
kDa
2
1
1
2

sapiens OX = 9606 GN = MGST3 PE = 1 SV = 1

Mitochondrial import receptor subunit TOM40 homolog
38
kDa
2
0
0
0

OS = Homo sapiens OX = 9606 GN = TOMM40 PE = 1

SV = 1

Mucin-19 OS = Homo sapiens OX = 9606 GN = MUC19
805
kDa
2
0
0
0

PE = 1 SV = 3

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3,
30
kDa
2
4
0
4

mitochondrial OS = Homo sapiens OX = 9606

GN = NDUFS3 PE = 1 SV = 1

Nascent polypeptide-associated complex subunit alpha,
205
kDa
2
6
0
4

muscle-specific form OS = Homo sapiens OX = 9606

GN = NACA PE = 1 SV = 1

Nicotinamide phosphoribosyltransferase OS = Homo
56
kDa
2
2
0
3

sapiens OX = 9606 GN = NAMPT PE = 1 SV = 1

Non-histone chromosomal protein HMG-14 OS = Homo
12
kDa
2
11
3
6

sapiens OX = 9606 GN = HMGN1 PE = 1 SV = 1

Nucleolar protein 11 OS = Homo sapiens OX = 9606
81
kDa
2
0
0
0

GN = NOL11 PE = 1 SV = 1

Obg-like ATPase 1 OS = Homo sapiens OX = 9606
45
kDa
2
4
0
3

GN = OLA1 PE = 1 SV = 2

PDZ and LIM domain protein 5 OS = Homo sapiens
64
kDa
2
3
0
2

GN = PDLIM5 PE = 1 SV = 5

Peroxiredoxin-2 OS = Homo sapiens OX = 9606
22
kDa
2
7
0
1

GN = PRDX2 PE = 1 SV = 5

Phospholipid-transporting ATPase IB OS = Homo sapiens
129
kDa
2
0
2
0

OX = 9606 GN = ATP8A2 PE = 1 SV = 3

Phosphoserine aminotransferase OS = Homo sapiens
40
kDa
2
0
0
0

OX = 9606 GN = PSAT1 PE = 1 SV = 2

Plasminogen activator inhibitor 1 OS = Homo sapiens
45
kDa
2
90
41
29

OX = 9606 GN = SERPINE1 PE = 1 SV = 1

pre-rRNA processing protein FTSJ3 OS = Homo sapiens
97
kDa
2
3
0
1

OX = 9606 GN = FTSJ3 PE = 1 SV = 2

PRKC apoptosis WT1 regulator protein OS = Homo
37
kDa
2
0
1
6

sapiens OX = 9606 GN = PAWR PE = 1 SV = 1

Proteasome activator complex subunit 2 OS = Homo
27
kDa
2
0
0
2

sapiens OX = 9606 GN = PSME2 PE = 1 SV = 4

Proteasome subunit alpha type-5 OS = Homo sapiens
26
kDa
2
2
0
2

OX = 9606 GN = PSMA5 PE = 1 SV = 3

Proteasome subunit alpha type-7 OS = Homo sapiens
28
kDa
2
7
0
2

OX = 9606 GN = PSMA7 PE = 1 SV = 1

Proteasome subunit beta type-2 OS = Homo sapiens
23
kDa
2
0
0
4

OX = 9606 GN = PSMB2 PE = 1 SV = 1

Protein flightless-1 homolog OS = Homo sapiens
145
kDa
2
0
0
1

OX = 9606 GN = FLII PE = 1 SV = 2

Protein SEC13 homolog OS = Homo sapiens OX = 9606
36
kDa
2
4
0
4

GN = SEC13 PE = 1 SV = 3

Ras-related protein Rab-5C OS = Homo sapiens OX = 9606
23
kDa
2
7
0
3

GN = RAB5C PE = 1 SV = 2

Ras-related protein Rab-7a OS = Homo sapiens OX = 9606
23
kDa
2
0
0
2

GN = RAB7A PE = 1 SV = 1

Remodeling and spacing factor 1 OS = Homo sapiens
164
kDa
2
9
0
0

GN = RSF1 PE = 1 SV = 2

Serine beta-lactamase-like protein LACTB,
61
kDa
2
13
5
3

mitochondrial OS = Homo sapiens OX = 9606 GN = LACTB

PE = 1 SV = 2

Serine/arginine-rich splicing factor 1 OS = Homo sapiens
28
kDa
2
7
0
2

GN = SRSF1 PE = 1 SV = 2

Structural maintenance of chromosomes protein 1A
143
kDa
2
7
0
0

OS = Homo sapiens OX = 9606 GN = SMC1A PE = 1 SV = 2

SWISS-PROT: P02777 (Bos taurus) similar to Platelet
24
kDa
2
3
3
3

factor 4

SWISS-PROT: Q2UVX4 (Bos taurus) Complement C3
187
kDa
2
7
6
4

precursor

SWISS-PROT: Q95121 (Bos taurus) Pigment epithelium-
46
kDa
2
0
3
3

derived factor precursor

Transaldolase OS = Homo sapiens OX = 9606
38
kDa
2
0
0
3

GN = TALDO1 PE = 1 SV = 2

Translationally-controlled tumor protein OS = Homo
20
kDa
2
0
0
2

sapiens OX = 9606 GN = TPT1 PE = 1 SV = 1

Translocon-associated protein subunit alpha OS = Homo
32
kDa
2
5
3
5

sapiens OX = 9606 GN = SSR1 PE = 1 SV = 3

Transmembrane emp24 domain-containing protein 10
25
kDa
2
0
6
8

OS = Homo sapiens OX = 9606 GN = TMED10 PE = 1 SV = 2

Transmembrane emp24 domain-containing protein 9
27
kDa
2
0
1
2

OS = Homo sapiens OX = 9606 GN = TMED9 PE = 1 SV = 2

TREMBL: Q1RMN8 (Bos taurus) Similar to
25
kDa
2
0
0
0

Immunoglobulin lambda-like polypeptide 1

Tripeptidyl-peptidase 1 OS = Homo sapiens GN = TPP1
61
kDa
2
0
2
3

PE = 1 SV = 2

1,4-alpha-glucan-branching enzyme OS = Homo sapiens
80
kDa
1
0
0
3

OX = 9606 GN = GBE1 PE = 1 SV = 3

1-phosphatidylinositol 4,5-bisphosphate
139
kDa
1
0
0
2

phosphodiesterase beta-3 OS = Homo sapiens GN = PLCB3

PE = 1 SV = 2

28S ribosomal protein S35, mitochondrial OS = Homo
37
kDa
1
2
0
2

sapiens GN = MRPS35 PE = 1 SV = 1

40S ribosomal protein S30 OS = Homo sapiens OX = 9606
7
kDa
1
0
3
2

GN = FAU PE = 1 SV = 1

60S ribosomal protein L11 OS = Homo sapiens OX = 9606
20
kDa
1
18
1
3

GN = RPL11 PE = 1 SV = 2

60S ribosomal protein L35a OS = Homo sapiens
13
kDa
1
0
2
2

OX = 9606 GN = RPL35A PE = 1 SV = 2

60S ribosomal protein L37a OS = Homo sapiens
10
kDa
1
0
5
5

OX = 9606 GN = RPL37A PE = 1 SV = 2

Alpha-parvin OS = Homo sapiens OX = 9606 GN = PARVA
42
kDa
1
3
0
4

PE = 1 SV = 1

AT-rich interactive domain-containing protein 1A
242
kDa
1
3
0
0

OS = Homo sapiens OX = 9606 GN = ARID1 A PE = 1 SV = 3

Basigin OS = Homo sapiens OX = 9606 GN = BSG PE = 1
42
kDa
1
3
0
1

SV = 2

Biorientation of chromosomes in cell division protein 1-
330
kDa
1
0
0
3

like 1 OS = Homo sapiens OX = 9606 GN = BOD1L1 PE = 1

SV = 2

Cell division cycle 5-like protein OS = Homo sapiens
92
kDa
1
3
0
4

OX = 9606 GN = CDC5L PE = 1 SV = 2

Coactosin-like protein OS = Homo sapiens OX = 9606
16
kDa
1
0
0
2

GN = COTL1 PE = 1 SV = 3

Collagen alpha-1(III) chain OS = Homo sapiens OX = 9606
139
kDa
1
2
0
1

GN = COL3A1 PE = 1 SV = 4

Collagen alpha-2(I) chain OS = Homo sapiens OX = 9606
129
kDa
1
12
7
3

GN = COL1A2 PE = 1 SV = 7

Collagen alpha-2(V) chain OS = Homo sapiens OX = 9606
145
kDa
1
0
15
6

GN = COL5A2 PE = 1 SV = 3

Collagen alpha-6(VI) chain OS = Homo sapiens OX = 9606
247
kDa
1
0
3
2

GN = COL6A6 PE = 1 SV = 2

Complement component 1 Q subcomponent-binding
31
kDa
1
0
0
4

protein, mitochondrial OS = Homo sapiens OX = 9606

GN = C1QBP PE = 1 SV = 1

Cysteine and glycine-rich protein 1 OS = Homo sapiens
21
kDa
1
0
0
2

OX = 9606 GN = CSRP1 PE = 1 SV = 3

Cytochrome b-c1 complex subunit 9 OS = Homo sapiens
7
kDa
1
2
0
2

OX = 9606 GN = UQCR10 PE = 1 SV = 3

Cytochrome c1, heme protein, mitochondrial OS = Homo
35
kDa
1
0
0
3

sapiens OX = 9606 GN = CYC1 PE = 1 SV = 3

DDRGK domain-containing protein 1 OS = Homo sapiens
36
kDa
1
0
1
2

OX = 9606 GN = DDRGK1 PE = 1 SV = 2

Destrin OS = Homo sapiens OX = 9606 GN = DSTN PE = 1
19
kDa
1
3
0
6

SV = 3

Dihydrolipoyl dehydrogenase, mitochondrial OS = Homo
54
kDa
1
8
0
2

sapiens OX = 9606 GN = DLD PE = 1 SV = 2

DNA-directed RNA polymerases I, II, and III subunit
25
kDa
1
0
5
1

RPABC1 OS = Homo sapiens OX = 9606 GN = POLR2E

PE = 1 SV = 4

ELAV-like protein 1 OS = Homo sapiens OX = 9606
36
kDa
1
3
0
1

GN = ELAVL1 PE = 1 SV = 2

Eukaryotic translation initiation factor 3 subunit G
36
kDa
1
0
0
3

OS = Homo sapiens OX = 9606 GN = EIF3G PE = 1 SV = 2

Farnesyl pyrophosphate synthase OS = Homo sapiens
48
kDa
1
3
0
1

OX = 9606 GN = FDPS PE = 1 SV = 4

Fibrillin-1 OS = Homo sapiens OX = 9606 GN = FBN1
312
kDa
1
0
2
0

PE = 1 SV = 3

Fumarate hydratase, mitochondrial OS = Homo sapiens
55
kDa
1
0
0
2

GN = FH PE = 1 SV = 3

Growth/differentiation factor 15 OS = Homo sapiens
34
kDa
1
0
7
6

OX = 9606 GN = GDF15 PE = 1 SV = 3

Histone deacetylase complex subunit SAP18 OS = Homo
20
kDa
1
0
0
2

sapiens OX = 9606 GN = SAP18 PE = 1 SV = 1

Histone H1x OS = Homo sapiens OX = 9606 GN = H1FX
22
kDa
1
0
0
2

PE = 1 SV = 1

Hydrocephalus-inducing protein homolog OS = Homo
576
kDa
1
0
1
0

sapiens OX = 9606 GN = HYDIN PE = 1 SV = 3

Insulin-like growth factor 2 mRNA-binding protein 3
64
kDa
1
18
2
0

OS = Homo sapiens GN = IGF2BP3 PE = 1 SV = 2

Isoform 2 of Adipocyte plasma membrane-associated
32
kDa
1
0
0
3

protein OS = Homo sapiens OX = 9606 GN = APMAP

Isoform 2 of Aspartate aminotransferase, mitochondrial
43
kDa
1
0
0
3

OS = Homo sapiens OX = 9606 GN = GOT2

Isoform 2 of BH3-interacting domain death agonist
27
kDa
1
4
0
0

OS = Homo sapiens OX = 9606 GN = BID

Isoform 2 of DnaJ homolog subfamily A member 3,
50
kDa
1
0
0
3

mitochondrial OS = Homo sapiens OX = 9606

GN = DNAJA3

Isoform 2 of Glia-derived nexin OS = Homo sapiens
44
kDa
1
8
0
0

OX = 9606 GN = SERPINE2

Isoform 2 of Histone deacetylase 2 OS = Homo sapiens
52
kDa
1
4
0
1

OX = 9606 GN = HDAC2

Isoform 2 of Lysosomal protective protein OS = Homo
52
kDa
1
1
0
2

sapiens OX = 9606 GN = CTSA

Isoform 2 of Lysosome membrane protein 2 OS = Homo
38
kDa
1
4
0
0

sapiens OX = 9606 GN = SCARB2

Isoform 2 of Myosin phosphatase Rho-interacting protein
118
kDa
1
13
0
0

OS = Homo sapiens OX = 9606 GN = MPRIP

Isoform 2 of NADH dehydrogenase [ubiquinone] 1 alpha
25
kDa
1
13
1
3

subcomplex subunit 13 OS = Homo sapiens OX = 9606

GN = NDUFA13

Isoform 2 of NADH dehydrogenase [ubiquinone] iron-
52
kDa
1
5
0
1

sulfur protein 2, mitochondrial OS = Homo sapiens

OX = 9606 GN = NDUFS2

Isoform 2 of Nesprin-2 OS = Homo sapiens OX = 9606
799
kDa
1
12
1
0

GN = SYNE2

Isoform 2 of Nuclear pore complex protein Nup214
213
kDa
1
0
0
3

OS = Homo sapiens OX = 9606 GN = NUP214

Isoform 2 of Phenylalanine--tRNA ligase alpha subunit
54
kDa
1
7
1
4

OS = Homo sapiens OX = 9606 GN = FARSA

Isoform 2 of Probable 28S rRNA (cytosine(4447)-C(5))-
89
kDa
1
6
0
6

methyltransferase OS = Homo sapiens OX = 9606

GN = NOP2

Isoform 2 of Protein FAM98A OS = Homo sapiens
55
kDa
1
2
0
3

OX = 9606 GN = FAM98A

Isoform 2 of Protein TFG OS = Homo sapiens OX = 9606
43
kDa
1
4
0
4

GN = TFG

Isoform 2 of Pyruvate dehydrogenase E1 component
37
kDa
1
7
0
3

subunit beta, mitochondrial OS = Homo sapiens OX = 9606

GN = PDHB

Isoform 2 of UTP--glucose-1-phosphate
56
kDa
1
3
0
7

uridylyltransferase OS = Homo sapiens OX = 9606

GN = UGP2

Isoform 2 of V-type proton ATPase 116 kDa subunit a
96
kDa
1
11
0
3

isoform 1 OS = Homo sapiens OX = 9606 GN = ATP6V0A1

Isoform 2B of Cytoplasmic dynein 1 intermediate chain 2
71
kDa
1
16
1
3

OS = Homo sapiens OX = 9606 GN = DYNC1I2

Isoform 3 of Activating signal cointegrator 1 complex
77
kDa
1
6
0
1

subunit 2 OS = Homo sapiens OX = 9606 GN = ASCC2

Isoform 3 of Apoptosis-inducing factor 1, mitochondrial
66
kDa
1
3
0
4

OS = Homo sapiens OX = 9606 GN = AIFM1

Isoform 3 of Calumenin OS = Homo sapiens OX = 9606
38
kDa
1
1
0
2

GN = CALU

Isoform 3 of Fragile X mental retardation syndrome-
60
kDa
1
4
0
1

related protein 1 OS = Homo sapiens OX = 9606

GN = FXR1

Isoform 3 of GRB10-interacting GYF protein 2
149
kDa
1
0
0
0

OS = Homo sapiens OX = 9606 GN = GIGYF2

Isoform 3 of Pyrroline-5-carboxylate reductase 1,
36
kDa
1
8
0
0

mitochondrial OS = Homo sapiens OX = 9606 GN = PYCR1

Isoform 3 of Ras-related protein R-Ras2 OS = Homo
20
kDa
1
5
0
1

sapiens GN = RRAS2

Isoform 3 of Signal peptidase complex catalytic subunit
21
kDa
1
2
1
3

SEC11A OS = Homo sapiens OX = 9606 GN = SEC11A

Isoform 4 of Cadherin-13 OS = Homo sapiens OX = 9606
83
kDa
1
23
6
2

GN = CDH13

Isoform 4 of Dipeptidyl peptidase 3 OS = Homo sapiens
79
kDa
1
0
0
2

OX = 9606 GN = DPP3

Isoform 4 of Dynamin-1-like protein OS = Homo sapiens
81
kDa
1
2
0
2

OX = 9606 GN = DNM1L

Isoform 4 of Dynamin-2 OS = Homo sapiens OX = 9606
98
kDa
1
13
0
6

GN = DNM2

Isoform 4 of Nexilin OS = Homo sapiens OX = 9606
73
kDa
1
28
12
7

GN = NEXN

Isoform 5 of Obscurin OS = Homo sapiens OX = 9606
925
kDa
1
0
0
1

GN = OBSCN

Isoform 6 of RNA-binding protein EWS OS = Homo
63
kDa
1
6
0
6

sapiens OX = 9606 GN = EWSR1

Isoform Heart of ATP synthase subunit gamma,
33
kDa
1
6
0
4

mitochondrial OS = Homo sapiens OX = 9606

GN = ATP5F1C

Isoform Mitochondrial of Lysine--tRNA ligase
71
kDa
1
4
0
1

OS = Homo sapiens OX = 9606 GN = KARS

Leucine-rich repeat-containing protein 17 OS = Homo
52
kDa
1
11
9
4

sapiens OX = 9606 GN = LRRC17 PE = 2 SV = 1

Leucyl-cystinyl aminopeptidase OS = Homo sapiens
117
kDa
1
4
3
2

OX = 9606 GN = LNPEP PE = 1 SV = 3

LIM and SH3 domain protein 1 OS = Homo sapiens
30
kDa
1
1
0
3

OX = 9606 GN = LASP1 PE = 1 SV = 2

Matrix metalloproteinase-14 OS = Homo sapiens
66
kDa
1
0
0
2

OX = 9606 GN = MMP14 PE = 1 SV = 3

Microtubule-associated protein RP/EB family member 1
30
kDa
1
4
0
4

OS = Homo sapiens OX = 9606 GN = MAPRE1 PE = 1 SV = 3

Mitochondrial 2-oxoglutarate/malate carrier protein
34
kDa
1
7
0
1

OS = Homo sapiens OX = 9606 GN = SLC25A11 PE = 1

SV = 3

Mitochondrial fission 1 protein OS = Homo sapiens
17
kDa
1
0
0
3

OX = 9606 GN = FIS1 PE = 1 SV = 2

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
17
kDa
1
6
1
2

subunit 12 OS = Homo sapiens OX = 9606 GN = NDUFA12

PE = 1 SV = 1

PDZ domain-containing protein 4 OS = Homo sapiens
86
kDa
1
0
0
0

OX = 9606 GN = PDZD4 PE = 1 SV = 1

Peroxisomal membrane protein PEX14 OS = Homo
41
kDa
1
3
0
2

sapiens OX = 9606 GN = PEX14 PE = 1 SV = 1

Platelet-activating factor acetylhydrolase IB subunit beta
26
kDa
1
6
0
1

OS = Homo sapiens GN = PAFAH1B2 PE = 1 SV = 1

Podocalyxin OS = Homo sapiens GN = PODXL PE = 1
59
kDa
1
0
0
2

SV = 2

Prolyl 3-hydroxylase 3 OS = Homo sapiens OX = 9606
82
kDa
1
0
0
2

GN = P3H3 PE = 1 SV = 1

Prolyl 4-hydroxylase subunit alpha-2 OS = Homo sapiens
61
kDa
1
2
0
0

OX = 9606 GN = P4HA2 PE = 1 SV = 1

Proteasome subunit alpha type-6 OS = Homo sapiens
27
kDa
1
8
0
1

OX = 9606 GN = PSMA6 PE = 1 SV = 1

Proteasome subunit beta type-5 OS = Homo sapiens
28
kDa
1
2
0
0

GN = PSMB5 PE = 1 SV = 3

Protein CYR61 OS = Homo sapiens OX = 9606
42
kDa
1
0
27
24

GN = CYR61 PE = 1 SV = 1

Protein mago nashi homolog OS = Homo sapiens
17
kDa
1
7
0
0

OX = 9606 GN = MAGOH PE = 1 SV = 1

RNA-binding protein 14 OS = Homo sapiens OX = 9606
69
kDa
1
18
2
5

GN = RBM14 PE = 1 SV = 2

RuvB-like 1 OS = Homo sapiens OX = 9606 GN = RUVBL1
50
kDa
1
18
0
2

PE = 1 SV = 1

Splicing factor 3B subunit 4 OS = Homo sapiens
44
kDa
1
0
0
2

OX = 9606 GN = SF3B4 PE = 1 SV = 1

Splicing factor U2AF 26 kDa subunit OS = Homo sapiens
4
kDa
1
0
2
1

OX = 9606 GN = U2AF1L4 PE = 4 SV = 1

SWISS-PROT: P04258 (Bos taurus) Similar to Collagen
138
kDa
1
9
0
0

alpha 1(III) chain

TREMBL: A2I7N3; Q27984 (Bos taurus) SERPINA3-7
47
kDa
1
5
1
1

Unconventional myosin-Ie OS = Homo sapiens OX = 9606
127
kDa
1
20
5
4

GN = MYO1E PE = 1 SV = 2

Vacuolar protein sorting-associated protein VTA1
34
kDa
1
0
0
2

homolog OS = Homo sapiens OX = 9606 GN = VTA1 PE = 1

SV = 1

Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 3
43
kDa
1
8
1
2

OS = Homo sapiens GN = HACD3 PE = 1 SV = 2

von Willebrand factor A domain-containing protein 1
47
kDa
1
7
0
0

OS = Homo sapiens OX = 9606 GN = VWA1 PE = 1 SV = 1

(Bos taurus) 63 kDa protein
63
kDa
0
55
0
0

10 kDa heat shock protein, mitochondrial OS = Homo
11
kDa
0
6
0
0

sapiens GN = HSPE1 PE = 1 SV = 2

1-phosphatidylinositol 3-phosphate 5-kinase OS = Homo
237
kDa
0
0
0
2

sapiens OX = 9606 GN = PIKFYVE PE = 1 SV = 3

26S protease regulatory subunit 10B OS = Homo sapiens
46
kDa
0
9
0
0

GN = PSMC6 PE = 1 SV = 1

26S protease regulatory subunit 6A OS = Homo sapiens
49
kDa
0
30
0
0

GN = PSMC3 PE = 1 SV = 3

26S proteasome non-ATPase regulatory subunit 14
35
kDa
0
17
0
0

OS = Homo sapiens GN = PSMD14 PE = 1 SV = 1

26S proteasome non-ATPase regulatory subunit 8
33
kDa
0
3
0
0

OS = Homo sapiens GN = PSMD8 PE = 1 SV = 1

28S ribosomal protein S34, mitochondrial OS = Homo
26
kDa
0
2
0
0

sapiens GN = MRPS34 PE = 1 SV = 2

39S ribosomal protein L11, mitochondrial OS = Homo
21
kDa
0
7
0
1

sapiens GN = MRPL11 PE = 1 SV = 1

39S ribosomal protein L34, mitochondrial OS = Homo
20
kDa
0
8
0
0

sapiens GN = MRPL34 PE = 1 SV = 1

3-ketoacyl-CoA thiolase, mitochondrial OS = Homo
42
kDa
0
0
0
2

sapiens OX = 9606 GN = ACAA2 PE = 1 SV = 2

40S ribosomal protein S13 OS = Homo sapiens OX = 9606
17
kDa
0
85
19
19

GN = RPS13 PE = 1 SV = 2

40S ribosomal protein S15a OS = Homo sapiens
11
kDa
0
25
0
0

GN = RPS15A PE = 1 SV = 1

40S ribosomal protein S18 OS = Homo sapiens
18
kDa
0
51
0
0

GN = RPS18 PE = 1 SV = 3

40S ribosomal protein S28 OS = Homo sapiens
8
kDa
0
6
0
0

GN = RPS28 PE = 1 SV = 1

40S ribosomal protein S29 OS = Homo sapiens OX = 9606
7
kDa
0
16
1
1

GN = RPS29 PE = 1 SV = 2

40S ribosomal protein S3a OS = Homo sapiens
30
kDa
0
53
0
0

GN = RPS3A PE = 1 SV = 2

40S ribosomal protein S4, Y isoform 1 OS = Homo
29
kDa
0
0
0
9

sapiens OX = 9606 GN = RPS4Y1 PE = 1 SV = 2

40S ribosomal protein SA (Fragment) OS = Homo sapiens
29
kDa
0
8
0
0

GN = RPSA PE = 1 SV = 8

60S acidic ribosomal protein P2 OS = Homo sapiens
12
kDa
0
50
0
0

GN = RPLP2 PE = 1 SV = 1

60S ribosomal protein L13a OS = Homo sapiens
24
kDa
0
33
0
0

GN = RPL13A PE = 1 SV = 2

60S ribosomal protein L14 OS = Homo sapiens
23
kDa
0
34
0
0

GN = RPL14 PE = 1 SV = 4

60S ribosomal protein L18a OS = Homo sapiens
21
kDa
0
31
0
0

GN = RPL18A PE = 1 SV = 2

60S ribosomal protein L23a (Fragment) OS = Homo
18
kDa
0
32
0
0

sapiens GN = RPL23A PE = 1 SV = 1

60S ribosomal protein L29 OS = Homo sapiens
18
kDa
0
6
0
0

GN = RPL29 PE = 1 SV = 2

60S ribosomal protein L32 (Fragment) OS = Homo
16
kDa
0
20
0
0

sapiens GN = RPL32 PE = 1 SV = 1

60S ribosomal protein L34 OS = Homo sapiens OX = 9606
13
kDa
0
0
3
3

GN = RPL34 PE = 1 SV = 3

60S ribosomal protein L35 OS = Homo sapiens
15
kDa
0
24
0
0

GN = RPL35 PE = 1 SV = 2

60S ribosomal protein L38 OS = Homo sapiens OX = 9606
8
kDa
0
0
5
4

GN = RPL38 PE = 1 SV = 2

78 kDa glucose-regulated protein OS = Homo sapiens
72
kDa
0
188
0
0

GN = HSPA5 PE = 1 SV = 2

A disintegrin and metalloproteinase with thrombospondin
105
kDa
0
12
3
0

motifs 1 OS = Homo sapiens OX = 9606 GN = ADAMTS1

PE = 1 SV = 4

Actin-related protein 10 OS = Homo sapiens
46
kDa
0
3
0
0

GN = ACTR10 PE = 1 SV = 1

Actin-related protein 2/3 complex subunit 1B OS = Homo
41
kDa
0
28
0
0

sapiens GN = ARPC1B PE = 1 SV = 3

ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2
36
kDa
0
3
5
2

OS = Homo sapiens OX = 9606 GN = BST1 PE = 1 SV = 2

Aminopeptidase N OS = Homo sapiens GN = ANPEP
110
kDa
0
194
0
0

PE = 1 SV = 4

Angiopoietin-related protein 4 OS = Homo sapiens
45
kDa
0
1
3
0

OX = 9606 GN = ANGPTL4 PE = 1 SV = 2

Annexin A3 OS = Homo sapiens OX = 9606 GN = ANXA3
36
kDa
0
0
0
3

PE = 1 SV = 3

Annexin A4 OS = Homo sapiens OX = 9606 GN = ANXA4
36
kDa
0
0
0
2

PE = 1 SV = 4

AP-2 complex subunit sigma OS = Homo sapiens
19
kDa
0
3
0
0

GN = AP2S1 PE = 1 SV = 1

Arf-GAP with Rho-GAP domain, ANK repeat and PH
170
kDa
0
0
0
2

domain-containing protein 3 OS = Homo sapiens

OX = 9606 GN = ARAP3 PE = 1 SV = 1

ATP synthase subunit epsilon-like protein, mitochondrial
6
kDa
0
3
0
0

OS = Homo sapiens GN = ATP5EP2 PE = 3 SV = 1

ATP synthase subunit g, mitochondrial OS = Homo
11
kDa
0
6
0
0

sapiens GN = ATP5L PE = 1 SV = 3

ATPase ASNA1 OS = Homo sapiens GN = ASNA1PE = 1
39
kDa
0
2
0
0

SV = 2

ATPase, H+ transporting, lysosomal accessory protein 1,
32
kDa
0
7
0
0

isoform CRA_c OS = Homo sapiens GN = ATP6AP1 PE = 1

SV = 1

ATP-dependent DNA helicase Q1 OS = Homo sapiens
73
kDa
0
2
0
0

GN = RECQL PE = 1 SV = 3

Barrier-to-autointegration factor OS = Homo sapiens
10
kDa
0
24
0
0

GN = BANF1 PE = 1 SV = 1

Basement membrane-specific heparan sulfate
469
kDa
0
4914
0
0

proteoglycan core protein OS = Homo sapiens

GN = HSPG2 PE = 1 SV = 4

Beta-catenin-like protein 1 OS = Homo sapiens
65
kDa
0
2
0
0

GN = CTNNBL1 PE = 1 SV = 1

Beta-galactosidase OS = Homo sapiens GN = GLB1 PE = 1
76
kDa
0
3
0
0

SV = 2

Biglycan OS = Homo sapiens OX = 9606 GN = BGN PE = 1
42
kDa
0
0
23
0

SV = 2

Bone morphogenetic protein 1 OS = Homo sapiens
111
kDa
0
14
3
0

OX = 9606 GN = BMP1 PE = 1 SV = 2

Brain acid soluble protein 1 OS = Homo sapiens
23
kDa
0
10
0
0

GN = BASP1 PE = 1 SV = 2

C-1-tetrahydrofolate synthase, cytoplasmic OS = Homo
102
kDa
0
2
0
0

sapiens GN = MTHFD1 PE = 1 SV = 3

Calmodulin OS = Homo sapiens GN = CALM1 PE = 1
17
kDa
0
24
0
0

SV = 2

Calpain small subunit 1 OS = Homo sapiens
34
kDa
0
34
0
0

GN = CAPNS1 PE = 1 SV = 1

Carboxypeptidase M OS = Homo sapiens GN = CPM PE = 1
51
kDa
0
5
0
0

SV = 2

Cardiomyopathy-associated protein 5 OS = Homo sapiens
449
kDa
0
2
0
0

GN = CMYA5 PE = 1 SV = 3

Casein kinase II subunit alpha OS = Homo sapiens
45
kDa
0
10
1
1

OX = 9606 GN = CSNK2A1 PE = 1 SV = 1

CD2-associated protein OS = Homo sapiens GN = CD2AP
71
kDa
0
9
0
0

PE = 1 SV = 1

CD59 glycoprotein OS = Homo sapiens OX = 9606
14
kDa
0
0
3
0

GN = CD59 PE = 1 SV = 1

Chloride intracellular channel protein 4 OS = Homo
29
kDa
0
2
0
0

sapiens GN = CLIC4 PE = 1 SV = 4

Chloride intracellular channel protein 6 OS = Homo
73
kDa
0
2
0
0

sapiens GN = CLIC6 PE = 2 SV = 3

Chromobox protein homolog 1 (Fragment) OS = Homo
19
kDa
0
5
0
0

sapiens GN = CBX1 PE = 1 SV = 1

Coiled-coil domain-containing protein 124 OS = Homo
26
kDa
0
6
0
0

sapiens GN = CCDC124 PE = 1 SV = 1

Coiled-coil domain-containing protein 30 OS = Homo
91
kDa
0
2
0
0

sapiens GN = CCDC30 PE = 2 SV = 1

Coiled-coil-helix-coiled-coil-helix domain-containing
13
kDa
0
2
0
0

protein 1 OS = Homo sapiens GN = CHCHD1 PE = 1 SV = 1

Collagen alpha-1(II) chain OS = Homo sapiens OX = 9606
142
kDa
0
2
1
1

GN = COL2A1 PE = 1 SV = 3

Collagen alpha-1(VI) chain OS = Homo sapiens
108
kDa
0
3
0
0

GN = COL6A1 PE = 1 SV = 1

Collagen alpha-1(X) chain OS = Homo sapiens
66
kDa
0
3
0
0

GN = COL10A1 PE = 1 SV = 2

Collagen alpha-1(XXIII) chain OS = Homo sapiens
52
kDa
0
2
0
0

GN = COL23A1 PE = 1 SV = 1

Collagen alpha-1(XXVII) chain OS = Homo sapiens
187
kDa
0
1
0
2

OX = 9606 GN = COL27A1 PE = 1 SV = 1

Collagen alpha-2(IX) chain OS = Homo sapiens OX = 9606
65
kDa
0
0
0
0

GN = COL9A2 PE = 1 SV = 2

Collagen triple helix repeat-containing protein 1
26
kDa
0
3
1
1

OS = Homo sapiens OX = 9606 GN = CTHRC1 PE = 1 SV = 1

Connective tissue growth factor OS = Homo sapiens
38
kDa
0
4
6
2

OX = 9606 GN = CTGF PE = 1 SV = 2

COP9 signalosome complex subunit 5 OS = Homo sapiens
38
kDa
0
2
0
0

GN = COPS5 PE = 1 SV = 4

Coronin-1B OS = Homo sapiens GN = CORO1B PE = 1
54
kDa
0
9
0
0

SV = 1

Cullin-1 OS = Homo sapiens GN = CUL1 PE = 1 SV = 2
90
kDa
0
3
0
0

Cytochrome c (Fragment) OS = Homo sapiens GN = CYCS
11
kDa
0
3
0
0

PE = 1 SV = 1

Cytochrome c oxidase subunit 4 isoform 1, mitochondrial
20
kDa
0
5
0
0

OS = Homo sapiens GN = COX4I1 PE = 1 SV = 1

Cytoplasmic aconitate hydratase OS = Homo sapiens
98
kDa
0
0
0
2

OX = 9606 GN = ACO1 PE = 1 SV = 3

Cytosolic non-specific dipeptidase OS = Homo sapiens
53
kDa
0
10
0
8

OX = 9606 GN = CNDP2 PE = 1 SV = 2

Death-associated protein kinase 3 OS = Homo sapiens
53
kDa
0
6
0
0

OX = 9606 GN = DAPK3 PE = 1 SV = 1

Deoxyribose-phosphate aldolase OS = Homo sapiens
35
kDa
0
0
0
3

OX = 9606 GN = DERA PE = 1 SV = 2

Desmoglein-1 OS = Homo sapiens GN = DSG1 PE = 1
114
kDa
0
6
0
0

SV = 2

DNA damage-binding protein 1 OS = Homo sapiens
127
kDa
0
14
0
3

OX = 9606 GN = DDB1 PE = 1 SV = 1

DNA topoisomerase 1 OS = Homo sapiens GN = TOP1
91
kDa
0
10
0
0

PE = 1 SV = 2

DNA-directed RNA polymerase II subunit RPB1
217
kDa
0
11
0
0

OS = Homo sapiens OX = 9606 GN = POLR2A PE = 1 SV = 2

DNA-directed RNA polymerase II subunit RPB2
134
kDa
0
14
0
0

OS = Homo sapiens GN = POLR2B PE = 1 SV = 1

DNA-directed RNA polymerase II subunit RPB3
31
kDa
0
9
0
0

OS = Homo sapiens GN = POLR2C PE = 1 SV = 2

DNA-directed RNA polymerase II subunit RPB4
13
kDa
0
6
0
0

OS = Homo sapiens GN = POLR2D PE = 1 SV = 1

DNA-directed RNA polymerases I, II, and III subunit
17
kDa
0
2
3
0

RPABC3 OS = Homo sapiens OX = 9606 GN = POLR2H

PE = 1 SV = 4

DnaJ homolog subfamily B member 11 OS = Homo
41
kDa
0
0
0
4

sapiens OX = 9606 GN = DNAJB11 PE = 1 SV = 1

Dolichol-phosphate mannosyltransferase subunit 1
30
kDa
0
2
0
0

OS = Homo sapiens GN = DPM1 PE = 1 SV = 1

Dolichyl-diphosphooligosaccharide--protein
94
kDa
0
2
0
0

glycosyltransferase subunit STT3B OS = Homo sapiens

GN = STT3B PE = 1 SV = 1

Doublecortin domain-containing protein 2 OS = Homo
53
kDa
0
17
0
2

sapiens OX = 9606 GN = DCDC2 PE = 1 SV = 2

Double-stranded RNA-binding protein Staufen homolog
63
kDa
0
15
4
4

1 OS = Homo sapiens OX = 9606 GN = STAU1 PE = 1 SV = 2

Dynactin subunit 2 OS = Homo sapiens GN = DCTN2
44
kDa
0
6
0
2

PE = 1 SV = 4

Dynein heavy chain 10, axonemal OS = Homo sapiens
515
kDa
0
1
0
2

OX = 9606 GN = DNAH10 PE = 1 SV = 4

EBNA1 binding protein 2, isoform CRA_d OS = Homo
41
kDa
0
5
0
0

sapiens GN = EBNA1BP2 PE = 1 SV = 1

Ectonucleotide pyrophosphatase/phosphodiesterase
105
kDa
0
0
0
2

family member 1 OS = Homo sapiens OX = 9606

GN = ENPP1 PE = 1 SV = 2

EH domain-containing protein 4 OS = Homo sapiens
61
kDa
0
5
0
3

OX = 9606 GN = EHD4 PE = 1 SV = 1

Elongation factor Tu, mitochondrial OS = Homo sapiens
50
kDa
0
9
0
0

GN = TUFM PE = 1 SV = 2

Emerin OS = Homo sapiens GN = EMD PE = 1 SV = 1
29
kDa
0
6
0
0

Epoxide hydrolase 1 OS = Homo sapiens OX = 9606
53
kDa
0
0
0
3

GN = EPHX1 PE = 1 SV = 1

ER lumen protein-retaining receptor 3 OS = Homo sapiens
25
kDa
0
5
0
0

GN = KDELR3 PE = 2 SV = 1

Eukaryotic translation initiation factor 3 subunit E
52
kDa
0
8
0
0

OS = Homo sapiens GN = EIF3E PE = 1 SV = 1

Eukaryotic translation initiation factor 3 subunit F
38
kDa
0
14
0
0

OS = Homo sapiens GN = EIF3F PE = 1 SV = 1

Eukaryotic translation initiation factor 3 subunit H
40
kDa
0
5
0
0

OS = Homo sapiens GN = EIF3H PE = 1 SV = 1

FACT complex subunit SPT16 OS = Homo sapiens
120
kDa
0
7
0
0

GN = SUPT16H PE = 1 SV = 1

Far upstream element-binding protein 1 OS = Homo
68
kDa
0
3
0
1

sapiens OX = 9606 GN = FUBP1 PE = 1 SV = 3

Fascin OS = Homo sapiens GN = FSCN1 PE = 1 SV = 3
55
kDa
0
12
0
0

Fibrous sheath-interacting protein 2 OS = Homo sapiens
781
kDa
0
0
2
1

OX = 9606 GN = FSIP2 PE = 2 SV = 4

Filaggrin OS = Homo sapiens GN = FLG PE = 1 SV = 3
435
kDa
0
3
0
0

Filaggrin-2 OS = Homo sapiens GN = FLG2 PE = 1 SV = 1
248
kDa
0
2
0
0

Flotillin-2 OS = Homo sapiens GN = FLOT2 PE = 1 SV = 1
53
kDa
0
13
0
0

Galectin-3 OS = Homo sapiens GN = LGALS3 PE = 1 SV = 5
26
kDa
0
39
0
0

Galectin-3-binding protein OS = Homo sapiens OX = 9606
65
kDa
0
4
0
3

GN = LGALS3BP PE = 1 SV = 1

Galectin-8 OS = Homo sapiens OX = 9606 GN = LGALS8
36
kDa
0
5
2
0

PE = 1 SV = 4

Glutamate dehydrogenase 1, mitochondrial OS = Homo
61
kDa
0
4
0
0

sapiens OX = 9606 GN = GLUD1 PE = 1 SV = 2

Glutathione peroxidase 1 OS = Homo sapiens GN = GPX1
22
kDa
0
3
0
2

PE = 1 SV = 4

Glycylpeptide N-tetradecanoyltransferase 2 OS = Homo
57
kDa
0
2
0
0

sapiens GN = NMT2 PE = 1 SV = 1

Glypican-6 OS = Homo sapiens GN = GPC6 PE = 1 SV = 1
63
kDa
0
14
0
0

Golgi-associated plant pathogenesis-related protein 1
17
kDa
0
20
0
0

OS = Homo sapiens GN = GLIPR2 PE = 1 SV = 3

Gremlin-1 OS = Homo sapiens OX = 9606 GN = GREM1
21
kDa
0
0
3
0

PE = 1 SV = 1

Guanine nucleotide-binding protein G(I)/G(S)/G(O)
8
kDa
0
6
0
0

subunit gamma-12 OS = Homo sapiens GN = GNG12 PE = 1

SV = 3

Guanine nucleotide-binding protein G(k) subunit alpha
41
kDa
0
17
0
0

OS = Homo sapiens GN = GNAI3 PE = 1 SV = 3

Hamartin OS = Homo sapiens GN = TSC1 PE = 1 SV = 2
130
kDa
0
0
0
2

Heat shock-related 70 kDa protein 2 OS = Homo sapiens
70
kDa
0
0
0
24

OX = 9606 GN = HSPA2 PE = 1 SV = 1

Hemicentin-2 OS = Homo sapiens OX = 9606
542
kDa
0
0
0
0

GN = HMCN2 PE = 2 SV = 3

Heparan sulfate glucosamine 3-O-sulfotransferase 6
37
kDa
0
3
0
0

OS = Homo sapiens GN = HS3ST6 PE = 1 SV = 2

Heterogeneous nuclear ribonucleoprotein A0 OS = Homo
31
kDa
0
15
0
0

sapiens GN = HNRNPA0 PE = 1 SV = 1

Heterogeneous nuclear ribonucleoprotein H2 OS = Homo
49
kDa
0
14
0
0

sapiens GN = HNRNPH2 PE = 1 SV = 1

Homeobox protein Hox-B3 OS = Homo sapiens OX = 9606
44
kDa
0
5
0
0

GN = HOXB3 PE = 2 SV = 2

Hornerin OS = Homo sapiens GN = HRNR PE = 1 SV = 2
282
kDa
0
15
0
0

Hsc70-interacting protein (Fragment) OS = Homo sapiens
16
kDa
0
2
0
0

GN = ST13 PE = 1 SV = 1

Hyaluronan and proteoglycan link protein 1 OS = Homo
40
kDa
0
0
0
0

sapiens OX = 9606 GN = HAPLN1 PE = 2 SV = 2

Hyaluronan and proteoglycan link protein 3 OS = Homo
41
kDa
0
6
0
0

sapiens GN = HAPLN3 PE = 2 SV = 1

Intercellular adhesion molecule 1 OS = Homo sapiens
58
kDa
0
16
0
0

GN = ICAM1 PE = 1 SV = 2

Interleukin enhancer-binding factor 2 OS = Homo sapiens
39
kDa
0
29
0
0

GN = ILF2 PE = 1 SV = 1

Isocitrate dehydrogenase [NADP] cytoplasmic
47
kDa
0
7
0
0

OS = Homo sapiens GN = IDH1 PE = 1 SV = 2

Isoform 1 of Gamma-adducin OS = Homo sapiens
76
kDa
0
7
0
1

OX = 9606 GN = ADD3

Isoform 1 of Polypyrimidine tract-binding protein 3
57
kDa
0
5
0
3

OS = Homo sapiens OX = 9606 GN = PTBP3

Isoform 1 of Synaptic functional regulator FMR1
67
kDa
0
5
0
1

OS = Homo sapiens OX = 9606 GN = FMR1

Isoform 2 of 2,4-dienoyl-CoA reductase, mitochondrial
35
kDa
0
8
0
1

OS = Homo sapiens OX = 9606 GN = DECR1

Isoform 2 of A-kinase anchor protein 13 OS = Homo
308
kDa
0
2
0
0

sapiens OX = 9606 GN = AKAP13

Isoform 2 of Ankyrin repeat domain-containing protein
274
kDa
0
0
0
0

17 OS = Homo sapiens OX = 9606 GN = ANKRD17

Isoform 2 of AP-2 complex subunit mu OS = Homo
49
kDa
0
9
0
1

sapiens OX = 9606 GN = AP2M1

Isoform 2 of Bcl-2-associated transcription factor 1
106
kDa
0
4
0
0

OS = Homo sapiens OX = 9606 GN = BCLAF1

Isoform 2 of Cadherin-2 OS = Homo sapiens OX = 9606
97
kDa
0
7
0
2

GN = CDH2

Isoform 2 of Calponin-1 OS = Homo sapiens OX = 9606
31
kDa
0
1
5
8

GN = CNN1

Isoform 2 of Chromodomain Y-like protein OS = Homo
61
kDa
0
4
0
0

sapiens GN = CDYL

Isoform 2 of Collagen alpha-1(VII) chain OS = Homo
292
kDa
0
70
2
1

sapiens OX = 9606 GN = COE7A1

Isoform 2 of Cyclin-Y OS = Homo sapiens GN = CCNY
37
kDa
0
3
0
0

Isoform 2 of Cysteine-rich protein 2 OS = Homo sapiens
30
kDa
0
5
0
0

OX = 9606 GN = CRIP2

Isoform 2 of DnaJ homolog subfamily C member 10
86
kDa
0
4
0
0

OS = Homo sapiens GN = DNAJC10

Isoform 2 of Fibroblast growth factor 2 OS = Homo
23
kDa
0
13
3
1

sapiens OX = 9606 GN = FGF2

Isoform 2 of Fibulin-2 OS = Homo sapiens OX = 9606
132
kDa
0
6
0
0

GN = FBLN2

Isoform 2 of GDNF family receptor alpha-1 OS = Homo
51
kDa
0
8
0
0

sapiens GN = GFRA1

Isoform 2 of Glycogen phosphorylase, liver form
93
kDa
0
2
0
1

OS = Homo sapiens OX = 9606 GN = PYGL

Isoform 2 of Golgin subfamily A member 5 OS = Homo
78
kDa
0
0
0
0

sapiens OX = 9606 GN = GOLGA5

Isoform 2 of H/ACA ribonucleoprotein complex subunit
21
kDa
0
1
1
2

1 OS = Homo sapiens OX = 9606 GN = GAR1

Isoform 2 of Helicase SRCAP OS = Homo sapiens
337
kDa
0
2
0
0

OX = 9606 GN = SRCAP

Isoform 2 of Histone-binding protein RBBP4 OS = Homo
48
kDa
0
6
0
0

sapiens OX = 9606 GN = RBBP4

Isoform 2 of Histone-lysine N-methyltransferase, H3
267
kDa
0
6
0
1

lysine-36 and H4 lysine-20 specific OS = Homo sapiens

OX = 9606 GN = NSD1

Isoform 2 of Insulin-like growth factor-binding protein 7
29
kDa
0
54
13
7

OS = Homo sapiens OX = 9606 GN = IGFBP7

Isoform 2 of Interferon-inducible double-stranded RNA-
33
kDa
0
4
1
1

dependent protein kinase activator A OS = Homo sapiens

OX = 9606 GN = PRKRA

Isoform 2 of KH domain-containing, RNA-binding,
30
kDa
0
8
0
0

signal transduction-associated protein 3 OS = Homo

sapiens GN = KHDRBS3

Isoform 2 of Lactadherin OS = Homo sapiens
35
kDa
0
25
2
1

GN = MFGE8

Isoform 2 of L-amino-acid oxidase OS = Homo sapiens
65
kDa
0
2
0
1

OX = 9606 GN = IL4I1

Isoform 2 of Macrophage-capping protein OS = Homo
37
kDa
0
3
0
0

sapiens GN = CAPG

Isoform 2 of Matrilin-2 OS = Homo sapiens OX = 9606
105
kDa
0
37
8
5

GN = MATN2

Isoform 2 of Mesoderm-specific transcript homolog
38
kDa
0
0
0
4

protein OS = Homo sapiens OX = 9606 GN = MEST

Isoform 2 of Microtubule-associated protein 1A
306
kDa
0
4
2
3

OS = Homo sapiens OX = 9606 GN = MAP1A

Isoform 2 of Midkine OS = Homo sapiens OX = 9606
10
kDa
0
4
2
2

GN = MDK

Isoform 2 of Monoacylglycerol lipase ABHD12
46
kDa
0
2
0
0

OS = Homo sapiens GN = ABHD12

Isoform 2 of Multidrug resistance protein 1 OS = Homo
134
kDa
0
1
0
2

sapiens OX = 9606 GN = ABCB1

Isoform 2 of Myosin-11 OS = Homo sapiens GN = MYH11
228
kDa
0
161
37
0

Isoform 2 of Myosin-14 OS = Homo sapiens OX = 9606
232
kDa
0
141
26
26

GN = MYH14

Isoform 2 of NADH dehydrogenase [ubiquinone] 1 beta
14
kDa
0
1
0
2

subcomplex subunit 4 OS = Homo sapiens OX = 9606

GN = NDUFB4

Isoform 2 of Nuclear receptor corepressor 1 OS = Homo
259
kDa
0
0
2
0

sapiens OX = 9606 GN = NCOR1

Isoform 2 of Periostin OS = Homo sapiens OX = 9606
87
kDa
0
0
5
5

GN = POSTN

Isoform 2 of Pescadillo homolog OS = Homo sapiens
67
kDa
0
5
1
0

OX = 9606 GN = PES1

Isoform 2 of Platelet-derived growth factor subunit B
26
kDa
0
1
3
1

OS = Homo sapiens OX = 9606 GN = PDGFB

Isoform 2 of Protein ELYS OS = Homo sapiens OX = 9606
256
kDa
0
0
2
0

GN = AHCTF1

Isoform 2 of Ran-binding protein 3 OS = Homo sapiens
60
kDa
0
5
0
0

OX = 9606 GN = RANBP3

Isoform 2 of Regulator of chromosome condensation
48
kDa
0
16
0
0

OS = Homo sapiens OX = 9606 GN = RCC1

Isoform 2 of Retinol-binding protein 1 OS = Homo
17
kDa
0
0
0
2

sapiens OX = 9606 GN = RBP1

Isoform 2 of RNA-binding protein 39 OS = Homo sapiens
59
kDa
0
0
0
2

GN = RBM39

Isoform 2 of RNA-binding protein 8A OS = Homo sapiens
20
kDa
0
5
0
1

OX = 9606 GN = RBM8A

Isoform 2 of Ryanodine receptor 1 OS = Homo sapiens
565
kDa
0
1
0
2

OX = 9606 GN = RYR1

Isoform 2 of SCO-spondin OS = Homo sapiens OX = 9606
139
kDa
0
3
0
0

GN = SSPO

Isoform 2 of Semaphorin-7A OS = Homo sapiens
73
kDa
0
3
1
3

OX = 9606 GN = SEMA7A

Isoform 2 of Septin-8 OS = Homo sapiens OX = 9606
50
kDa
0
12
0
3

GN = SEPT8

Isoform 2 of Serine/threonine-protein phosphatase
28
kDa
0
5
0
1

PGAM5, mitochondrial OS = Homo sapiens OX = 9606

GN = PGAM5

Isoform 2 of SH3 domain-containing kinase-binding
69
kDa
0
2
0
2

protein 1 OS = Homo sapiens OX = 9606 GN = SH3KBP1

Isoform 2 of Signal recognition particle receptor subunit
67
kDa
0
3
0
1

alpha OS = Homo sapiens OX = 9606 GN = SRPRA

Isoform 2 of Signal-induced proliferation-associated 1-
197
kDa
0
0
0
0

like protein 1 OS = Homo sapiens OX = 9606

GN = SIPA1L1

Isoform 2 of Sorting nexin-27 OS = Homo sapiens
60
kDa
0
4
0
0

GN = SNX27

Isoform 2 of Spectrin beta chain, erythrocytic OS = Homo
268
kDa
0
8
0
2

sapiens OX = 9606 GN = SPTB

Isoform 2 of Testis-expressed protein 10 OS = Homo
104
kDa
0
2
0
0

sapiens OX = 9606 GN = TEX10

Isoform 2 of Tissue factor pathway inhibitor 2 OS = Homo
26
kDa
0
9
6
0

sapiens OX = 9606 GN = TFPI2

Isoform 2 of Tyrosine-protein kinase BAZ1B OS = Homo
170
kDa
0
4
0
0

sapiens OX = 9606 GN = BAZ1B

Isoform 2 of UDP-glucuronosyltransferase 1-6
30
kDa
0
4
0
0

OS = Homo sapiens OX = 9606 GN = UGT1A6

Isoform 2 of Vesicle-associated membrane protein-
33
kDa
0
3
0
1

associated protein A OS = Homo sapiens OX = 9606

GN = VAPA

Isoform 2 of Voltage-dependent calcium channel subunit
123
kDa
0
2
1
0

alpha-2/delta-l OS = Homo sapiens OX = 9606

GN = CACNA2D1

Isoform 2 of Y-box-binding protein 3 OS = Homo sapiens
32
kDa
0
15
0
1

OX = 9606 GN = YBX3

Isoform 2 of Zinc finger homeobox protein 4 OS = Homo
397
kDa
0
2
0
0

sapiens OX = 9606 GN = ZFHX4

Isoform 3 of 1-phosphatidylinositol 4,5-bisphosphate
136
kDa
0
3
0
0

phosphodiesterase beta-4 OS = Homo sapiens OX = 9606

GN = PLCB4

Isoform 3 of Alpha-adducin OS = Homo sapiens
84
kDa
0
2
0
0

GN = ADD1

Isoform 3 of Cytoskeleton-associated protein 5
226
kDa
0
3
0
0

OS = Homo sapiens OX = 9606 GN = CKAP5

Isoform 3 of DnaJ homolog subfamily C member 11
57
kDa
0
2
0
1

OS = Homo sapiens GN = DNAJC11

Isoform 3 of E3 ubiquitin-protein ligase CHFR
69
kDa
0
0
0
0

OS = Homo sapiens OX = 9606 GN = CHFR

Isoform 3 of H/ACA ribonucleoprotein complex subunit
48
kDa
0
13
1
1

DKC1 OS = Homo sapiens OX = 9606 GN = DKC1

Isoform 3 of Histone-lysine N-methyltransferase 2D
594
kDa
0
1
0
1

OS = Homo sapiens OX = 9606 GN = KMT2D

Isoform 3 of Latent-transforming growth factor beta-
169
kDa
0
34
0
0

binding protein 4 OS = Homo sapiens OX = 9606

GN = LTBP4

Isoform 3 of Malate dehydrogenase, cytoplasmic
39
kDa
0
3
0
0

OS = Homo sapiens OX = 9606 GN = MDH1

Isoform 3 of Putative oxidoreductase GLYR1 OS = Homo
60
kDa
0
4
0
0

sapiens OX = 9606 GN = GLYR1

Isoform 3 of Scaffold attachment factor B1 OS = Homo
103
kDa
0
3
0
0

sapiens GN = SAFB

Isoform 3 of Torsin-1A-interacting protein 1 OS = Homo
66
kDa
0
5
0
0

sapiens GN = TOR1AIP1

Isoform 4 of CD109 antigen OS = Homo sapiens
160
kDa
0
18
0
0

GN = CD109

Isoform 4 of FYVE and coiled-coil domain-containing
169
kDa
0
0
0
0

protein 1 OS = Homo sapiens OX = 9606 GN = FYCO1

Isoform 4 of IQ domain-containing protein N OS = Homo
147
kDa
0
0
0
3

sapiens OX = 9606 GN = IQCN

Isoform 4 of Kinesin-like protein KIF24 OS = Homo
129
kDa
0
2
0
0

sapiens OX = 9606 GN = KIF24

Isoform 4 of Latent-transforming growth factor beta-
187
kDa
0
1
4
1

binding protein 1 OS = Homo sapiens OX = 9606

GN = LTBP1

Isoform 4 of Protein diaphanous homolog 3 OS = Homo
136
kDa
0
2
0
0

sapiens GN = DIAPH3

Isoform 5 of E1A-binding protein p400 OS = Homo
340
kDa
0
1
0
0

sapiens OX = 9606 GN = EP400

Isoform 5 of Immunoglobulin-like and fibronectin type
384
kDa
0
3
0
2

III domain-containing protein 1 OS = Homo sapiens

OX = 9606 GN = IGFN1

Isoform 5 of LIM domain only protein 7 OS = Homo
158
kDa
0
8
0
0

sapiens GN = LMO7

Isoform 5 of Papilin OS = Homo sapiens OX = 9606
136
kDa
0
17
1
1

GN = PAPLN

Isoform 6 of Treacle protein OS = Homo sapiens
148
kDa
0
2
0
0

OX = 9606 GN = TCOF1

Isoform B of Collagen alpha-1(XI) chain OS = Homo
182
kDa
0
0
1
2

sapiens OX = 9606 GN = COL11Al

Isoform B of Collagen alpha-6(IV) chain OS = Homo
164
kDa
0
5
2
0

sapiens OX = 9606 GN = COL4A6

Isoform B of DnaJ homolog subfamily B member 6
27
kDa
0
0
1
2

OS = Homo sapiens OX = 9606 GN = DNAJB6

Isoform B of Methyl-CpG-binding protein 2 OS = Homo
53
kDa
0
11
1
0

sapiens OX = 9606 GN = MECP2

Isoform B of Ras-related C3 botulinum toxin substrate 1
23
kDa
0
3
0
0

OS = Homo sapiens OX = 9606 GN = RAC1

Isoform B of Transforming growth factor beta-2
51
kDa
0
5
1
2

proprotein OS = Homo sapiens OX = 9606 GN = TGFB2

Isoform Beta-3B of Integrin beta-3 OS = Homo sapiens
86
kDa
0
4
0
2

OX = 9606 GN = ITGB3

Isoform C of Fibulin-1 OS = Homo sapiens OX = 9606
74
kDa
0
13
0
8

GN = FBLN1

Isoform Long of Proteasome subunit alpha type-1
30
kDa
0
2
0
2

OS = Homo sapiens OX = 9606 GN = PSMA1

Isoform Non-brain of Clathrin light chain A OS = Homo
24
kDa
0
17
0
2

sapiens OX = 9606 GN = CLTA

Isoform Short of Laminin subunit gamma-2 OS = Homo
122
kDa
0
5
0
1

sapiens OX = 9606 GN = LAMC2

Keratin, type I cytoskeletal 14 OS = Homo sapiens
52
kDa
0
94
0
18

OX = 9606 GN = KRT14 PE = 1 SV = 4

Keratin, type I cytoskeletal 16 OS = Homo sapiens
51
kDa
0
99
0
0

GN = KRT16 PE = 1 SV = 4

Keratin, type I cytoskeletal 19 OS = Homo sapiens
44
kDa
0
753
0
0

GN = KRT19 PE = 1 SV = 4

Keratin, type II cuticular Hb5 OS = Homo sapiens
56
kDa
0
3
0
0

GN = KRT85 PE = 1 SV = 1

Keratin, type II cytoskeletal 1 OS = Homo sapiens
66
kDa
0
497
0
0

GN = KRT1 PE = 1 SV = 6

Keratin, type II cytoskeletal 5 OS = Homo sapiens
62
kDa
0
93
0
0

GN = KRT5 PE = 1 SV = 3

Keratin, type II cytoskeletal 6B OS = Homo sapiens
60
kDa
0
104
18
0

OX = 9606 GN = KRT6B PE = 1 SV = 5

Keratin, type II cytoskeletal 7 OS = Homo sapiens
51
kDa
0
0
0
135

OX = 9606 GN = KRT7 PE = 1 SV = 5

Kinesin-like protein KIFC2 OS = Homo sapiens OX = 9606
90
kDa
0
2
0
1

GN = KIFC2 PE = 2 SV = 1

Ladinin-1 OS = Homo sapiens OX = 9606 GN = LAD1
57
kDa
0
0
0
6

PE = 1 SV = 2

Laminin subunit beta-3 OS = Homo sapiens GN = LAMB3
130
kDa
0
10
0
0

PE = 1 SV = 1

Latent-transforming growth factor beta-binding protein 2
190
kDa
0
23
0
0

OS = Homo sapiens GN = LTBP2 PE = 1 SV = 1

Leucine zipper protein 1 OS = Homo sapiens OX = 9606
120
kDa
0
5
0
0

GN = LUZP1 PE = 1 SV = 2

Lipoamide acyltransferase component of branched-chain
53
kDa
0
6
4
8

alpha-keto acid dehydrogenase complex, mitochondrial

OS = Homo sapiens OX = 9606 GN = DBT PE = 1 SV = 3

Low-density lipoprotein receptor-related protein 1B
515
kDa
0
2
0
0

OS = Homo sapiens GN = LRP1B PE = 1 SV = 2

Low-density lipoprotein receptor-related protein 2
522
kDa
0
0
0
2

OS = Homo sapiens OX = 9606 GN = LRP2 PE = 1 SV = 3

Lysyl oxidase homolog 1 OS = Homo sapiens OX = 9606
63
kDa
0
24
1
0

GN = LOXL1 PE = 1 SV = 2

Magnesium transporter protein 1 OS = Homo sapiens
42
kDa
0
4
1
1

GN = MAGT1 PE = 1 SV = 1

MARCKS-related protein OS = Homo sapiens
20
kDa
0
4
0
0

GN = MARCKSL1 PE = 1 SV = 2

Metastasis-associated protein MTA2 OS = Homo sapiens
75
kDa
0
5
0
0

GN = MTA2 PE = 1 SV = 1

Microsomal glutathione S-transferase 1 OS = Homo
18
kDa
0
0
0
3

sapiens OX = 9606 GN = MGST1 PE = 1 SV = 1

Mitochondrial GTPase 1 OS = Homo sapiens OX = 9606
37
kDa
0
0
0
2

PE = 3 SV = 1

MKI67 FHA domain-interacting nucleolar
20
kDa
0
6
0
0

phosphoprotein (Fragment) OS = Homo sapiens

GN = NIFK PE = 1 SV = 1

Mucin-16 OS = Homo sapiens OX = 9606 GN = MUC16
1519
kDa
0
0
2
4

PE = 1 SV = 3

Myelin expression factor 2 OS = Homo sapiens OX = 9606
64
kDa
0
2
0
0

GN = MYEF2 PE = 1 SV = 3

Myosin light chain 6B OS = Homo sapiens OX = 9606
23
kDa
0
0
6
0

GN = MYL6B PE = 1 SV = 1

Myristoylated alanine-rich C-kinase substrate OS = Homo
32
kDa
0
11
0
0

sapiens GN = MARCKS PE = 1 SV = 4

N-acylneuraminate cytidylyltransferase OS = Homo
48
kDa
0
6
0
0

sapiens GN = CMAS PE = 1 SV = 2

NAD(P) transhydrogenase, mitochondrial OS = Homo
100
kDa
0
3
0
0

sapiens GN = NNT PE = 1 SV = 1

Nestin OS = Homo sapiens GN = NES PE = 1 SV = 2
177
kDa
0
18
0
0

Neurabin-2 OS = Homo sapiens GN = PPP1R9BPE = 1
89
kDa
0
3
0
0

SV = 1

Neurobeachin OS = Homo sapiens OX = 9606GN = NBEA
328
kDa
0
0
0
3

PE = 1 SV = 3

Nicotinate-nucleotide pyrophosphorylase [carboxylating]
31
kDa
0
0
0
4

OS = Homo sapiens OX = 9606 GN = QPRT PE = 1 SV = 3

Non-syndromic hearing impairment protein 5 OS = Homo
55
kDa
0
2
0
0

sapiens GN = DFNA5 PE = 1 SV = 2

Nuclear receptor-binding protein OS = Homo sapiens
61
kDa
0
5
0
0

GN = NRBP1 PE = 1 SV = 1

Nucleolar complex protein 3 homolog OS = Homo sapiens
93
kDa
0
5
0
0

GN = NOC3L PE = 1 SV = 1

Nucleolar complex protein 4 homolog OS = Homo sapiens
58
kDa
0
5
0
0

GN = NOC4L PE = 1 SV = 1

Nucleolar protein 58 OS = Homo sapiens GN = NOP58
60
kDa
0
6
0
0

PE = 1 SV = 1

Nucleolar transcription factor 1 OS = Homo sapiens
87
kDa
0
2
0
0

GN = UBTF PE = 1 SV = 1

Nucleoplasmin-3 OS = Homo sapiens GN = NPM3 PE = 1
19
kDa
0
3
0
0

SV = 3

Palladin OS = Homo sapiens OX = 9606 GN = PALLD
151
kDa
0
7
0
6

PE = 1 SV = 3

PDZ and LIM domain protein 1 OS = Homo sapiens
36
kDa
0
0
0
4

OX = 9606 GN = PDLIM1 PE = 1 SV = 4

PDZ and LIM domain protein 4 OS = Homo sapiens
35
kDa
0
3
0
0

GN = PDLIM4 PE = 1 SV = 2

Pentraxin-related protein PTX3 OS = Homo sapiens
42
kDa
0
23
0
0

GN = PTX3 PE = 1 SV = 3

Peptidyl-prolyl cis-trans isomerase B OS = Homo sapiens
24
kDa
0
52
0
0

GN = PPIB PE = 1 SV = 2

Peptidyl-prolyl cis-trans isomerase FKBP10 OS = Homo
64
kDa
0
3
0
0

sapiens GN = FKBP10 PE = 1 SV = 1

Peptidyl-prolyl cis-trans isomerase FKBP3 OS = Homo
25
kDa
0
8
0
0

sapiens GN = FKBP3 PE = 1 SV = 1

Periaxin OS = Homo sapiens OX = 9606 GN = PRX PE = 1
155
kDa
0
0
0
2

SV = 2

Periodic tryptophan protein 1 homolog OS = Homo
56
kDa
0
2
0
0

sapiens OX = 9606 GN = PWP1 PE = 1 SV = 1

Peroxiredoxin-1 (Fragment) OS = Homo sapiens
19
kDa
0
13
0
0

GN = PRDX1 PE = 1 SV = 1

Phosphoglycerate mutase 1 OS = Homo sapiens
29
kDa
0
11
0
0

GN = PGAM1 PE = 1 SV = 2

Pinin OS = Homo sapiens OX = 9606 GN = PNN PE = 1
82
kDa
0
6
2
4

SV = 5

Platelet-activating factor acetylhydrolase IB subunit
47
kDa
0
4
0
0

alpha OS = Homo sapiens OX = 9606 GN = PAFAH1B1

PE = 1 SV = 2

Poly [ADP-ribose] polymerase 1 OS = Homo sapiens
113
kDa
0
30
0
0

GN = PARP1 PE = 1 SV = 4

Poly(U)-binding-splicing factor PUF60 (Fragment)
57
kDa
0
3
0
0

OS = Homo sapiens GN = PUF60 PE = 1 SV = 1

Polymerase delta-interacting protein 3 OS = Homo sapiens
48
kDa
0
6
0
0

GN = POLDIP3 PE = 1 SV = 1

Polymerase I and transcript release factor OS = Homo
43
kDa
0
89
0
0

sapiens GN = PTRF PE = 1 SV = 1

Polyubiquitin-B OS = Homo sapiens GN = UBBPE = 1
17
kDa
0
111
0
0

SV = 1

POU domain, class 3, transcription factor 3 OS = Homo
50
kDa
0
20
0
0

sapiens GN = POU3F3 PE = 2 SV = 2

PR domain zinc finger protein 8 OS = Homo sapiens
72
kDa
0
2
0
0

GN = PRDM8 PE = 1 SV = 3

Prefoldin subunit 6 OS = Homo sapiens GN = PFDN6
15
kDa
0
3
0
0

PE = 1 SV = 1

Probable ATP-dependent RNA helicase DDX27
87
kDa
0
4
0
0

OS = Homo sapiens GN = DDX27 PE = 1 SV = 1

Probable global transcription activator SNF2L1
123
kDa
0
6
0
0

OS = Homo sapiens OX = 9606 GN = SMARCA1 PE = 1

SV = 2

Probable maltase-glucoamylase 2 OS = Homo sapiens
278
kDa
0
0
0
2

OX = 9606 GN = MGAM2 PE = 2 SV = 3

Procollagen galactosyltransferase 1 OS = Homo sapiens
72
kDa
0
3
0
0

GN = COLGALT1 PE = 1 SV = 1

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3
85
kDa
0
3
0
0

OS = Homo sapiens GN = PLOD3 PE = 1 SV = 1

Prolow-density lipoprotein receptor-related protein 1
505
kDa
0
2
0
0

OS = Homo sapiens GN = LRP1 PE = 1 SV = 2

Protein disulfide-isomerase OS = Homo sapiens
53
kDa
0
30
0
0

GN = P4HB PE = 1 SV = 2

Protein GREB1 OS = Homo sapiens GN = GREB1PE = 2
216
kDa
0
0
0
2

SV = 1

Protein kinase C delta-binding protein OS = Homo sapiens
31
kDa
0
20
0
0

GN = PRKCDBP PE = 1 SV = 1

Protein MAK16 homolog OS = Homo sapiens
35
kDa
0
2
0
0

GN = MAK16 PE = 1 SV = 2

Protein S100-A10 OS = Homo sapiens GN = S100A10
11
kDa
0
11
0
0

PE = 1 SV = 2

Protein S100-A13 OS = Homo sapiens GN = S100A13
11
kDa
0
5
0
0

PE = 1 SV = 1

Protein S100-A9 OS = Homo sapiens GN = S100A9 PE = 1
13
kDa
0
12
0
0

SV = 1

Protein-glutamine gamma-glutamyltransferase E
77
kDa
0
2
0
0

OS = Homo sapiens GN = TGM3 PE = 1 SV = 4

Pumilio homolog 3 OS = Homo sapiens GN = PUM3 PE = 1
74
kDa
0
6
0
0

SV = 3

Raftlin OS = Homo sapiens GN = RFTN1 PE = 1 SV = 4
63
kDa
0
3
0
0

Ras GTPase-activating-like protein IQGAP1 OS = Homo
189
kDa
0
135
0
0

sapiens GN = IQGAP1 PE = 1 SV = 1

Ras-related protein Rab-10 OS = Homo sapiens
23
kDa
0
13
0
0

GN = RAB10 PE = 1 SV = 1

Ras-related protein Rab-14 (Fragment) OS = Homo
20
kDa
0
8
0
0

sapiens GN = RAB14 PE = 1 SV = 1

Ras-related protein Rab-2A OS = Homo sapiens
24
kDa
0
5
0
1

GN = RAB2A PE = 1 SV = 1

Ras-related protein Ral-A OS = Homo sapiens GN = RALA
24
kDa
0
2
0
0

PE = 1 SV = 1

Regulation of nuclear pre-mRNA domain-containing
37
kDa
0
2
0
0

protein 1B OS = Homo sapiens GN = RPRD1B PE = 1 SV = 1

Replication protein A 32 kDa subunit OS = Homo sapiens
29
kDa
0
3
0
1

GN = RPA2 PE = 1 SV = 1

Replication protein A 70 kDa DNA-binding subunit
68
kDa
0
4
0
0

OS = Homo sapiens GN = RPA1 PE = 1 SV = 2

Reticulocalbin-1 OS = Homo sapiens GN = RCN1 PE = 1
39
kDa
0
7
0
0

SV = 1

Retinoic acid-induced protein 3 OS = Homo sapiens
40
kDa
0
0
0
2

OX = 9606 GN = GPRC5A PE = 1 SV = 2

Rho GTPase-activating protein 1 OS = Homo sapiens
50
kDa
0
8
0
0

GN = ARHGAP1 PE = 1 SV = 1

Ribosomal protein L19 OS = Homo sapiens GN = RPL19
23
kDa
0
21
0
0

PE = 1 SV = 1

Ribosome biogenesis protein BRX1 homolog OS = Homo
41
kDa
0
5
0
3

sapiens OX = 9606 GN = BRIX1 PE = 1 SV = 2

Ribosome biogenesis protein WDR12 OS = Homo sapiens
48
kDa
0
3
0
0

GN = WDR12 PE = 1 SV = 2

Ribosome biogenesis regulatory protein homolog
41
kDa
0
11
0
0

OS = Homo sapiens GN = RRS1 PE = 1 SV = 2

Ribosome production factor 2 homolog OS = Homo
36
kDa
0
3
0
0

sapiens GN = RPF2 PE = 1 SV = 2

RNA-binding protein 28 OS = Homo sapiens OX = 9606
86
kDa
0
2
0
2

GN = RBM28 PE = 1 SV = 3

RNA-binding protein 3 OS = Homo sapiens GN = RBM3
17
kDa
0
3
0
0

PE = 1 SV = 1

rRNA 2′-O-methyltransferase fibrillarin OS = Homo
34
kDa
0
23
0
0

sapiens GN = FBL PE = 1 SV = 2

Selenoprotein H OS = Homo sapiens GN = C11orf31 PE = 1
13
kDa
0
2
0
0

SV = 1

Semaphorin-3C OS = Homo sapiens GN = SEMA3C PE = 2
85
kDa
0
3
0
0

SV = 2

Serine protease 23 OS = Homo sapiens OX = 9606
43
kDa
0
7
7
5

GN = PRSS23 PE = 1 SV = 1

Serine protease HTRA3 OS = Homo sapiens OX = 9606
49
kDa
0
3
3
0

GN = HTRA3 PE = 1 SV = 2

Serine/threonine-protein phosphatase 2A catalytic
36
kDa
0
4
0
0

subunit beta isoform OS = Homo sapiens GN = PPP2CB

PE = 1 SV = 1

Serine/threonine-protein phosphatase PP1-beta catalytic
37
kDa
0
22
0
0

subunit OS = Homo sapiens GN = PPP1CB PE = 1 SV = 3

Serpin B3 OS = Homo sapiens GN = SERPINB3PE = 1
45
kDa
0
4
0
0

SV = 2

SH3 domain-binding protein 1 OS = Homo sapiens
76
kDa
0
2
0
0

GN = SH3BP1 PE = 1 SV = 3

Signal peptidase complex subunit 1 OS = Homo sapiens
12
kDa
0
2
0
0

GN = SPCS1 PE = 1 SV = 4

Signal peptidase complex subunit 3 OS = Homo sapiens
20
kDa
0
5
0
0

GN = SPCS3 PE = 1 SV = 1

Signal recognition particle 14 kDa protein OS = Homo
15
kDa
0
9
0
0

sapiens GN = SRP14 PE = 1 SV = 2

Signal-induced proliferation-associated 1-like protein 2
190
kDa
0
0
0
2

OS = Homo sapiens OX = 9606 GN = SIPA1L2 PE = 1 SV = 2

Single-stranded DNA-binding protein, mitochondrial
17
kDa
0
24
0
0

OS = Homo sapiens GN = SSBP1 PE = 1 SV = 1

SNW domain-containing protein 1 OS = Homo sapiens
61
kDa
0
4
0
0

GN = SNW1 PE = 1 SV = 1

Solute carrier family 2, facilitated glucose transporter
54
kDa
0
9
0
0

member 1 OS = Homo sapiens GN = SLC2A1 PE = 1 SV = 2

SPARC (Fragment) OS = Homo sapiens GN = SPARC
17
kDa
0
2
0
0

PE = 1 SV = 1

Spermatogenesis-associated serine-rich protein 2
60
kDa
0
2
0
0

OS = Homo sapiens GN = SPATS2 PE = 1 SV = 1

Sphingosine-1-phosphate lyase 1 OS = Homo sapiens
64
kDa
0
2
0
0

GN = SGPL1 PE = 1 SV = 3

Splicing factor 3B subunit 2 OS = Homo sapiens
98
kDa
0
7
0
0

GN = SF3B2 PE = 1 SV = 1

SRA stem-loop-interacting RNA-binding protein,
14
kDa
0
2
0
0

mitochondrial OS = Homo sapiens GN = SLIRP PE = 1

SV = 1

Structural maintenance of chromosomes protein 3
142
kDa
0
11
0
0

OS = Homo sapiens GN = SMC3 PE = 1 SV = 2

SWI/SNF-related matrix-associated actin-dependent
122
kDa
0
17
0
0

regulator of chromatin subfamily A member 5 OS = Homo

sapiens GN = SMARCA5 PE = 1 SV = 1

SWI/SNF-related matrix-associated actin-dependent
47
kDa
0
4
0
0

regulator of chromatin subfamily E member 1 OS = Homo

sapiens OX = 9606 GN = SMARCE1 PE = 1 SV = 2

SWISS-PROT: P01044-1 (Bos taurus) Isoform HMW of
69
kDa
0
3
0
0

Kininogen-1 precursor

SWISS-PROT: P02768-1 Tax_Id = 9606
69
kDa
0
0
5
13

Gene_Symbol = ALB Isoform 1 of Serum albumin

precursor

SWISS-PROT: Q3SZR3 (Bos taurus) Alpha-1-acid
23
kDa
0
2
0
0

glycoprotein precursor

SWISS-PROT: Q3TTY5 Tax_Id = 10090
71
kDa
0
27
7
7

Gene_Symbol = Krt2 Keratin, type II cytoskeletal 2

epidermal

SWISS-PROT: Q9D312 Tax_Id = 10090
49
kDa
0
6
0
4

Gene_Symbol = Krt20 Keratin, type I cytoskeletal 20

SWISS-PROT: Q9QWL7 Tax_Id = 10090
48
kDa
0
54
0
16

Gene_Symbol = Krt17 Keratin, type I cytoskeletal 17

Synaptosomal-associated protein 23 OS = Homo sapiens
23
kDa
0
6
0
0

GN = SNAP23 PE = 1 SV = 1

Tau-tubulin kinase 2 OS = Homo sapiens OX = 9606
182
kDa
0
0
0
0

GN = TTBK2 PE = 1 SV = 1

TBC1 domain family member 1 (Fragment) OS = Homo
98
kDa
0
2
0
0

sapiens GN = TBC1D1 PE = 1 SV = 3

T-complex protein 1 subunit alpha OS = Homo sapiens
60
kDa
0
98
0
0

GN = TCP1 PE = 1 SV = 1

Thyroid hormone receptor-associated protein 3
109
kDa
0
11
0
0

OS = Homo sapiens GN = THRAP3 PE = 1 SV = 2

Tight junction protein ZO-1 OS = Homo sapiens
188
kDa
0
3
0
0

GN = TJP1 PE = 1 SV = 1

Tight junction protein ZO-2 OS = Homo sapiens
141
kDa
0
3
0
0

GN = TJP2 PE = 4 SV = 1

Transcription factor A, mitochondrial OS = Homo sapiens
29
kDa
0
14
1
1

OX = 9606 GN = TFAM PE = 1 SV = 1

Transcription factor SOX-3 OS = Homo sapiens
45
kDa
0
2
0
0

GN = SOX3 PE = 1 SV = 2

Transforming growth factor-beta-induced protein ig-h3
75
kDa
0
670
73
58

OS = Homo sapiens OX = 9606 GN = TGFBI PE = 1 SV = 1

Translocator protein OS = Homo sapiens OX = 9606
19
kDa
0
0
0
3

GN = TSPO PE = 1 SV = 3

Transmembrane protein 165 OS = Homo sapiens
35
kDa
0
5
0
1

GN = TMEM165 PE = 1 SV = 1

TREMBL: Q0V8M9; Q9TRI0 (Bos taurus) similar to
100
kDa
0
7
0
0

inter-alpha (globulin) inhibitor H3 isoform 2

TREMBL: Q2KJC7; Q8HZM3 (Bos taurus) Periostin,
87
kDa
0
1
12
5

osteoblast specific factor

TREMBL: Q3SZH5 (Bos taurus) Similar to
45
kDa
0
11
4
2

Angiotensinogen

TREMBL: Q3T052; Q5EA67 (Bos taurus) Inter-alpha
102
kDa
0
10
5
1

(Globulin) inhibitor H4

TREMBL: Q6ISB0 Keratin, hair, basic, 4 - Homo sapiens
65
kDa
0
16
8
8

(Human).

TREMBL: Q6NXH9 Tax_Id = 10090
59
kDa
0
114
7
10

Gene_Symbol = Krt73 Keratin 73

TRIO and F-actin-binding protein OS = Homo sapiens
261
kDa
0
2
0
0

OX = 9606 GN = TRIOBP PE = 1 SV = 3

Tropomodulin-3 OS = Homo sapiens OX = 9606
40
kDa
0
47
21
13

GN = TMOD3 PE = 1 SV = 1

Tropomyosin 1 (Alpha), isoform CRA_f OS = Homo
37
kDa
0
162
0
0

sapiens GN = TPM1 PE = 1 SV = 1

Tropomyosin 1 (Alpha), isoform CRA_m OS = Homo
29
kDa
0
118
0
0

sapiens GN = TPM1 PE = 1 SV = 1

Tropomyosin alpha-3 chain OS = Homo sapiens
33
kDa
0
112
0
0

GN = TPM3 PE = 1 SV = 1

Tubby-related protein 2 (Fragment) OS = Homo sapiens
24
kDa
0
0
0
2

OX = 9606 GN = TULP2 PE = 4 SV = 1

Twinfilin-1 OS = Homo sapiens OX = 9606 GN = TWF1
40
kDa
0
1
1
4

PE = 1 SV = 3

Tyrosine-protein kinase OS = Homo sapiens GN = YES1
61
kDa
0
7
0
0

PE = 1 SV = 1

Tyrosine--tRNA ligase OS = Homo sapiens GN = YARS
44
kDa
0
6
0
0

PE = 1 SV = 1

U1 small nuclear ribonucleoprotein A (Fragment)
28
kDa
0
7
0
0

OS = Homo sapiens GN = SNRPA PE = 1 SV = 1

U3 small nucleolar ribonucleoprotein protein MPP10
79
kDa
0
6
0
0

OS = Homo sapiens GN = MPHOSPH10 PE = 1 SV = 2

U3 small nucleolar RNA-associated protein 14 Homolog
88
kDa
0
2
0
0

A OS = Homo sapiens OX = 9606 GN = UTP14A PE = 1

SV = 1

U4/U6.U5 tri-snRNP-associated protein 1 OS = Homo
90
kDa
0
4
0
0

sapiens GN = SART1 PE = 1 SV = 1

UAP56-interacting factor OS = Homo sapiens OX = 9606
36
kDa
0
3
0
0

GN = FYTTD1 PE = 1 SV = 3

Ubiquitin carboxyl-terminal hydrolase 24 OS = Homo
294
kDa
0
0
0
2

sapiens OX = 9606 GN = USP24 PE = 1 SV = 3

Unconventional myosin-Id OS = Homo sapiens OX = 9606
116
kDa
0
0
2
0

GN = MYO1D PE = 1 SV = 2

Unconventional myosin-VI OS = Homo sapiens
145
kDa
0
26
0
0

GN = MYO6 PE = 1 SV = 1

Unconventional myosin-XV OS = Homo sapiens
395
kDa
0
0
2
0

OX = 9606 GN = MYO15A PE = 1 SV = 2

Urokinase-type plasminogen activator OS = Homo sapiens
47
kDa
0
8
0
0

GN = PLAU PE = 1 SV = 1

UV excision repair protein RAD23 homolog B
43
kDa
0
5
0
0

OS = Homo sapiens GN = RAD23B PE = 1 SV = 1

Vacuolar protein sorting-associated protein 26A
38
kDa
0
5
0
3

OS = Homo sapiens OX = 9606 GN = VPS26A PE = 1 SV = 2

Very-long-chain enoyl-CoA reductase OS = Homo sapiens
36
kDa
0
6
0
0

GN = TECR PE = 1 SV = 1

Vesicle-trafficking protein SEC22b OS = Homo sapiens
25
kDa
0
6
0
0

GN = SEC22B PE = 1 SV = 4

V-type proton ATPase subunit B, brain isoform
57
kDa
0
16
0
0

OS = Homo sapiens GN = ATP6V1B2 PE = 1 SV = 3

V-type proton ATPase subunit d 1 OS = Homo sapiens
45
kDa
0
22
0
0

GN = ATP6V0D1 PE = 1 SV = 1

Zinc finger protein 469 OS = Homo sapiens OX = 9606
410
kDa
0
0
0
4

GN = ZNF469 PE = 2 SV = 3

C. Example 3—Proliferation of iPSCs on Amniotic Fluid Cell-Derived ECM

Induced pluripotent stem cells (iPSCs) were allowed to proliferate on an amniotic fluid cell-derived ECM (Matrix B) from Example 1 in culture using the following procedure: commercially available, cryopreserved iPSCs were thawed using a water bath at 37° C. Cell suspension was diluted into commercially available media for stem cell proliferation (Miltenyi Biotec MACS iPS Brew) and seeded onto the ECM at approximately 1,000 cells/cm′ in a 6-well-plate with 2 mL of media/well. No Rock inhibitor was used. At day 1, the full volume of media was aspirated gently from cells in culture and replaced with fresh media. Every 24 hours, full media was replaced with fresh media. Once cells began to approach confluence (as determined by brightfield microscopy), cells were passage manually, using a sterile needle to cut large colonies into approximately 100 smaller colonies and then re-plate those by physically lifting them off the dish with the sterile needle and placing them on a fresh plate of the ECM. This procedure can be repeated indefinitely.

A photomicrograph showing Day 0 and Day 2 culture of iPSCs on amniotic fluid cell-derived ECM and a bone marrow cell-derived ECM is shown in FIG. 4.

A plot of iPSC colony growth curves of iPSCs cultured in the presence of the amniotic fluid cell-derived ECM and a bone marrow cell-derived ECM is shown in FIG. 5.

As can be seen in FIG. 4 and FIG. 5, the iPSCs proliferated in culture in the presence of the amniotic fluid cell-derived ECM, whereas iPSCs cultured in the presence of a bone marrow cell-derived ECM had no growth.

D. Example 4—Preparation of a Cellular Construct of Mature Cardiomyocytes on an AFC-ECM and Maturation of Immature hiPSC-CMs on the AFC-ECM

Cellular constructs comprising monolayers of mature cardiomyocytes on extracellular matrices derived from cells derived in-vitro from amniotic fluid (AFC-ECMs) were prepared using the following method.

Using the methodology as outlined in Example 1, AFC-ECMs were prepared in 96-well plates (no silicone inserts were used). Using standard cell culture techniques, commercially available immature hiPSC-CMs from Cellular Dynamics International-FUJI (iCell® Cardiomyocytes) were plated on the AFC-ECMs. The immature hiPSC-CMs were plated at a density of 50,000 cells per well (96 well plate) or 200,000 cells per well (6 well plate), and were cultured for 7 days in RPMI media forming confluent monolayers of mature cardiomyocytes on the AFC-ECMs, thereby forming cellular constructs of mature cardiomyocyte monolayers on the AFC-ECMs.

Over the 7-day period, the immature hiPSC-CMs were observed to mature into the morphology and alignment of mature native adult cardiomyocytes as characterized by rod shaped cells with distinct sarcomere structure. For comparison purposes, iCell® immature hiPSC-CMs were also plated (no silicone inserts were used) in 96-well plates and cultured in a similar fashion on standard Matrigel™ ECM, and on a bone marrow cell-derived ECM (BM-ECM) as prepared by methods as disclosed in U.S. Pat. No. 8,084,023, herein incorporated by reference. Results of the studies are shown in photomicrographs of the cardiomyocytes on the different ECMs in FIGS. 6 to 21.

As can be seen in the FIGS. 6 to 14, the cardiomyocytes on the AFC-ECM are mature, rod shaped cells with distinct sarcomere structure resembling native adult cardiomyocytes. The morphology and sarcomere structure of the cardiomyocytes matured on AFC-ECM can be distinctly seen by the presence of rod shaped cells with a striped appearance identified by arrows in the photomicrograph of FIG. 14. The figures show the presence of fiber tracks on the AFC-ECM, and also show that the monolayer of mature cardiomyocytes is in alignment with the AFC-ECM which closely resembles characteristics found in native adult cardiomyocytes and native heart muscle tissue. By contrast, as can be seen in FIGS. 15 to 19 and FIGS. 20 to 21, the cardiomyocytes on the standard Matrigel™ ECM and BM-ECM respectively, resemble fetal-like cardiomyocytes and do not have the characteristics of native adult cardiomyocytes or native heart muscle tissue.

Thus, the immature hiPSC-CMs cultured on the AFC-ECM achieved a higher state of maturation than did the immature hiPSC-CMs cultured on the standard Matrigel™ ECM or the natural cell-derived ECM from bone marrow cells. It is evident that the hiPSC-CM morphology was affected differently by different ECM.

E. Example 5—High Throughput Cardiotoxicity Screen Testing of Drugs Using Cellular Construct of Mature Cardiomyocytes on an AFC-ECM

Cellular constructs of monolayers of mature cardiomyocytes on AFC-ECM were prepared as described in Example 4 using 96-well plates (no silicone inserts were used). After the 7-day maturation process the electrophysiology of each well was observed using a plate reader using the following high throughput screen method. FluoVolt™ dye in Hanks Balanced Salt Solution was loaded into each well. A high spatiotemporal CCD camera (SciMeasure DaVinci camera) combined with light emitting diodes (LEDs) as shown in the schematic in FIG. 22. The camera and lens combination were designed such that it allowed visualization of all the wells of the 96-well plate simultaneously with sufficient resolution to observe action potential and calcium wave propagation. Each plate was centered under the camera system, lighting was switched on and camera acquisition was initiated and electrophysiological activity was recorded. Experiments were performed at about 37° C. Spontaneous activity was recorded for at least 10 seconds and images were stored on a computer. After baseline readings were taken, 500 nM of the drug E4031 (a hERG channel blocker) was added to each well. Images were analyzed and action potential duration, conduction velocity, beat rate and activation patterns were quantified using image analysis software. For comparison purposes, immature hiPSC-CMs were cultured on standard Matrigel™ ECM and bone-marrow cell derived ECM (BM-ECM) in 96 well plates (no silicone inserts were used) as described in Example 4, and 500 nM of the drug E4031 (a hERG channel blocker) was analyzed in similar fashion as with the AFC-ECM studies. Results of the E4031 testing are shown in FIG. 23 and FIG. 24. As can be seen in FIG. 23, the recordings of the spontaneous action potentials recorded from the cardiomyocytes on the Matrigel™ ECM and BM-ECM showed that the drug E-4031 only caused action potential duration (APD) prolongation; however, on the mature cardiomyocytes on the AFC-ECM, the drug E-4031 caused APD prolongation plus Rotors (TdP-like arrhythmias) which are arrhythmia activation patterns consistent with what is known to occur in cases of TdP in humans. Thus, all three ECMs produced monolayers of cardiomyocytes that responded with predicted APD prolongation, but only the AFC-ECM produced monolayers of cardiomyocytes that revealed transition of APD prolongation to tachyarrhythmia, characteristic of TdP. As can be seen in FIG. 24, 100% of the cardiomyocytes on the AFC-ECM responded to the drug E4031 with rotors (TdP like arrhythmia).

In additional studies, the drugs domperidone (3 μM), disopyramide (100 μM), azimilide (10 μM), D,1 Sotalol (100 μM), ibutilide (0.10 μM), and Bepridil (10 μM) were tested with mature cardiomyocytes on AFC-ECM as prepared in Example 4 (no silicone inserts) in 96-well plates using the plate reader method described above. The results of the testing are shown in FIG. 25. As can be seen in the results, various types of arrhythmias, i.e., tachyarrhythmia (TA), quiescence (Q), early afterdepolarization (EAD), were caused by the various drugs as notated in the recordings. In response to drugs classified as high risk for causing TdP fatal arrhythmias in patients by the FDA—these are the range of arrhythmia types observed.

Various drugs shown in Table 3 and 4 below were also tested with mature cardiomyocytes on AFC-ECM as prepared in Example 4 (no silicone inserts) in 96-well plates using the plate reader method described above and observations for any arrhythmia detected and APD90 prolongation at 10 times the effective therapeutic plasma concentration (ETPC) were notated. The drugs were selected from the CiPA Initiative's list of compounds for validation and testing of CiPA and are classified as high risk, intermediate risk or low risk for causing fatal arrhythmias (TdPs) in patients. The complete list of CiPA compounds can be found at cipaproject.org/wp-content/uploads/sites/24/2016/05/CiPA-Compounds.pdf.

TABLE 3

APD90

Risk
Dose 1
Dose 2
Dose 3
Dose 4
Arrhythmia
Prolongation?

Drug
Category
(μM)
(μM)
(μM)
(μM)
Detected?
@10X ETPC

Tamoxifen
Low
0.1
0.5
1.0
10.0
No
No

Nifedipine
Low
0.001
0.01
0.1
1.0
Yes, Q
No,

Shortening

Nitrendipine
Low
0.00951
0.03004
0.09494
0.3
No
No,

Shortening

Mexiletine
Low
0.01
0.1
1.0
10.0
No
No

Ranolazine
Low
0.01
0.1
1.0
10.0
No
No

Domperidone
Intermediate
0.003
0.03
0.3
3.0
Yes, TA
Yes

Droperidol
Intermediate
0.03169
0.10014
0.31646
1.0
Yes, EAD
Yes

Clozapine
Intermediate
0.09507
0.30043
0.94937
3.0
No
Yes

Terfenadine
Intermediate
0.001
0.01
0.1
1.0
No
Yes

Disopyramide
High
0.100
1.00
10.00
100.00
Yes, EAD, TA
Yes

Quinidine
High
0.95
3.00
9.49
30.0
Yes, EAD
Yes

D, I Sotalol
High
0.1
1.0
10.0
100.00
Yes, EAD
Yes

Bepridil
High
0.01
0.10
1.00
10.0
Yes, Q
Yes

Dofetilide
High
0.0005
0.0010
0.0032
0.010
Yes, EAD
Yes

TABLE 4

APD90

Risk
Dose 1
Dose 2
Dose 3
Dose 4
Arrhythmia
Prolongation?

Drug
Category
(μM)
(μM)
(μM)
(μM)
Detected?
@10X ETPC

Diltiazem
Low
0.01
0.10
1.0
10.0
No
No, shortening

Loratadine
Low
0.00095
0.003
0.00949
0.03
No
No

Metoprolol
Low
3.169
10.0144
31.6456
100
Yes,
No

Verapamil
Low
0.001
0.01
0.1
1
No
No, Shortening

Astemizole
Intermediate
0.0001
0.001
0.01
0.1
Yes
Yes

Chlorpromazir
Intermediate
0.09507
0.30043
0.94937
3.0
NA
NA

Cisapride
Intermediate
0.00317
0.01001
0.03165
0.1
Yes
No

Pimozide
Intermediate
0.00095
0.003
0.00949
0.03
Yes
No

Risperidone
Intermediate
0.00317
0.01001
0.03165
0.1
No

Ondansetron
Intermediate
0.03
0.30
3.0
30.0
Yes, EAD
Yes

Azimilide
High
0.01
0.10
1.0
10.0
Yes, EAD
Yes

Ibutilide
High
0.0001
0.0010
0.0100
0.100
Yes, EAD
YeS

Vandetanib
High

Yes, EAD
Yes

Further analyses of the data from the drugs tested in Tables 3 and 4 are shown in FIGS. 26 to 29. FIG. 26 graphically shows the total number of arrhythmias observed per any dose of each drug compound. FIG. 27 graphically shows the relative occurrence of arrhythmias for each drug at specific clinically relevant doses, 10× the effective therapeutic plasma concentration (ETPC).

FIG. 28 graphically shows the action potential triangulation (APD90-APD30) in time (ms) for each drug. Triangulation is defined as the repolarization time from APD30 to APD90. Action potential triangulation (APD90-APD30) is used as a predictor for proarrhythmia of a drug. FIG. 29 shows the action potential triangulation in time (ms) for some drugs comparing cardiomyocyte assay performance of the cardiomyocytes on the AFC-ECM (SBS-AF Matrix) versus on Matrigel™ ECM.

FIG. 30 graphically shows the maximum drug-induced action potential triangulation of the listed drugs comparing cardiomyocyte performance of iCell® hiPSC-CMs from Cellular Dynamics (blank circles) versus Cor.4U® hiPSC-CMs from Ncardia (dark circles) at any concentration of the listed drugs. This figure is from publication Blinova et al, International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment, 2018, Cell Reports 24, 3582-3592. In contrast to FIG. 28, there is little stratification between high risk and intermediate risk compounds in the data set shown in FIG. 30. Thus, the AFC-ECM of this disclosure provides for the production of more mature cardiomyocytes with more realistic function and drug responsiveness than of other natural cell-derived ECMs or Matrigel™ ECM.

F. Example 6—Observations of a Cellular Construct of Mature Cardiomyocytes on an AFC-ECM

Cellular constructs of mature cardiomyocytes on an AFC-ECM were prepared following the procedures as described in Example 4 above with the following modifications as noted below:

AFC-ECM was deposited onto Thermanox coverslips to enable immunostaining of cells and imaging using laser scanning confocal microscopy (Nikon MR).

Matrigel™ ECM was applied to a separate subset of Thermanox coverslips for comparison.

Cells from Cellular Dynamics International-FUJI (iCell® Cardiomyocytes) were plated as monolayers on these Thermanox coverslips coated with each ECM at a density of 200,000 cells per well in 6 well plates.

After 7 days of incubation in cell culture media, cells were fixed in 3% paraformaldehyde and processed for immunocytochemistry with application of commercially available primary antibodies to determine cellular expression and localization in hiPSC-CMs. The following primary antibodies for key cardiac myofilament proteins were used: Troponin I, α-actinin, cardiac troponin T (cTnT), cardiac troponin I (cTnI) and N-cadherin. Commercially available fluorescently labelled secondary antibodies were used for detection. DAPI (4′,6-diamidino-2-phenylindole) fluorescent stain was used to mark the nuclei.

All procedures for cell labeling and visualization are as described in the following references incorporated by reference herein. Herron, T. J. et al. Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function. Circulation: Arrhythmia and Electrophysiology 9 (2016). da Rocha, M. A. et al. Deficient cMyBP-C protein expression during cardiomyocyte differentiation underlies human hypertrophic cardiomyopathy cellular phenotypes in disease specific human ES cell derived cardiomyocytes. J. Mol. Cell. Cardiol. 99, 197-206 (2016). da Rocha, A. M. et al. hiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High Throughput Pro-Arrhythmia Screen. Sci. Rep. 7, 13834 (2017).

Cell shape was quantified using fluorescent images analyzed in NIS Elements Software. Using cell area and perimeter, cellular circularity was quantified using the established mathematical equation; Circularity Index=4π*Area/Perimeter².

In some cases, mitochondria were stained using MitoTracker™ Red CMXRos (Thermo Fisher).

Results: Consistent with the results as seen in Example 4 above, data using fluorescent labeling and imaging demonstrates that the AFC-ECM promotes rapid (7-day) maturation of hiPSC-CMs, and shows that hiPSC-CMs cultured on Matrigel™ ECM are circular in shape and have disorganization of sarcomeres, whereas the same batch of hiPSC-CMs (isogenic coparator) cultured on AFC-ECM are rod shaped and have tight compaction/organization of sarcomeres and myofilaments.

The photomicrophraphs in FIG. 31 show hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for Troponin I, using DAPI to mark the nuclei. The photomicrophraphs in FIG. 32 show hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for α-actinin using DAPI to mark the nuclei. The photmicrographs in FIG. 33 show hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for cTnT and N Cadherin, using DAPI to mark the nuclei. As can be seen in FIGS. 31 to 33, the hiPSC-CMs cultured on Matrigel™ ECM are circular in shape and have disorganization of sarcomeres, whereas the same batch of hiPSC-CMs (isogenic coparator) cultured on AFC-ECM are rod shaped and have tight compaction/organization of sarcomeres and myofilaments. Some examples of the cells are identified with arrows as either circular cells or rod shaped cells and some examples of the sarcomeres are identified with arrows in FIGS. 31 to 33. The photomicrographs in FIG. 34 show a single hiPSC-CM cell cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for cTnT using DAPI to mark the nuclei and show that the cell cultured on Matrigel™ ECM is circular, whereas the cell cultured on AFC-ECM is rod shaped. The photomicrographs in FIG. 35 show a single hiPSC-CM cell cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for α-actinin using DAPI to mark the nuclei and show that the cell cultured on Matrigel™ ECM is circular, whereas the cell cultured on AFC-ECM is rod shaped. The graph in FIG. 36 shows a comparison of the cellular circularity of the single cells shown in FIG. 35 and shows a higher circularity index for the cell cultured on the Matrigel™ ECM indicating more roundness.

The photomicrographs in FIG. 37 show hiPSC-CMs cultured on Matrigel™ ECM vs. AFC-ECM with immunofluorescent staining for cTnI expression, using DAPI to mark the nuclei. FIG. 38 shows western blotting of hiPSC-CMs on Matrigel™ ECM and AFC-ECM for cTnI expression and GAPDH (glyceraldehyde 3-phosphate dehydrogenase). An analysis of the western blotting of FIG. 38 is shown in the graph of FIG. 39 showing the cTnI expression relative to GAPDH for the hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM. The analysis shows a higher cTnI expression/GAPDH ratio for the hiPSC-CMs on the AFC-ECM than the hiPSC-CMs on the Matrigel™ ECM which indicates a more robust cTnI expression from the hiPSC-CMs on the AFC-ECM than from the hiPSC-CMs on the Matrigel™ ECM.

The photomicrographs in FIG. 40 show hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM stained for mitochondria with MitoTracker Red and show that cells on AFC-ECM have more mitochondria and mitochondria with more polarized inner membrane potential as evidenced by greater red signal. The graph in FIG. 41 shows the MitoTraker™ Red fluorescence intensity/cardiomyocyte for hiPSC-CMs on Matrigel™ ECM vs. AFC-ECM and shows that the hiPSC-CMs on the AFC-ECM have higher MitoTraker™ Red fluorescence intensity indicating that these cells have more mitochondria and mitochondria with more polarized inner membrane potential than the hiPSC-CMs on the Matrigel™ ECM.

The photomicrographs (transmitted light) in FIG. 42 show hiPSC-CMs cultured on Matrigel™ ECM and AFC-ECM that were coated on microelectrode array (MEA) plates. As can be seen in FIG. 42, the hiPSC-CMs cultured on the Matrigel™ ECM are circular in shape and the hiPSC-CMs cultured on the AFC-ECM are rod shaped.

	Number	Date	Country
Parent	16797945	Feb 2020	US
Child	17531402		US

METHODS FOR THE MATURATION OF CARDIOMYOCYTES ON AMNIOTIC FLUID CELL-DERIVED ECM, CELLULAR CONSTRUCTS, AND USES FOR CARDIOTOXICITY AND PROARRHYTHMIC SCREENING OF DRUG COMPOUNDS

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