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TGFB2 TGFB2 DCN DCN TIMP1 TIMP1 MMP2 MMP2 TGFB1 TGFB1 COMP COMP COL1A1 COL1A1 AGXT2 AGXT2 BMP4 BMP4 SOX9 SOX9 TPH1 TPH1 ADAMTS2 ADAMTS2 CHAD CHAD SMAD2 SMAD2 TIMP2 TIMP2 MAPK3 MAPK3 NID1 NID1 VCAN VCAN LUM LUM KERA KERA REN REN HAPLN1 HAPLN1 ADAMTS19 ADAMTS19 BMP6 BMP6 ADAMTS5 ADAMTS5 MMP16 MMP16 HAS2 HAS2 MMP14 MMP14 DUOX1 DUOX1 FBN1 FBN1 BGN BGN MT1E MT1E ELN ELN SMURF1 SMURF1 CCN2 CCN2 ADAMTS4 ADAMTS4 MMP9 MMP9 ENG ENG BMP2 BMP2 EDN1 EDN1 ADAMTS6 ADAMTS6 DUOX2 DUOX2 LAMA1 LAMA1 ACAN ACAN CD44 CD44 TNF TNF LAMA2 LAMA2 SOD2-2 SOD2-2 PECAM1 PECAM1 MMP12 MMP12 CDH5 CDH5
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splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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TGFB2Transforming growth factor beta-2 proprotein; Transforming growth factor beta-2 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. Transforming growth factor beta-2: Multifunctional protein that regulates various processes such as angiogenesis and heart development. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth fact [...] (442 aa)
DCNDecorin; May affect the rate of fibrils formation. (359 aa)
TIMP1Metalloproteinase inhibitor 1; Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it [...] (207 aa)
MMP272 kDa type IV collagenase; Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta- type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3 [...] (660 aa)
TGFB1Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. Transforming growth factor beta-1: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form fo [...] (390 aa)
COMPCartilage oligomeric matrix protein; May play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin. Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors. Could play a role in the pathogenesis of osteoarthritis. Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BI [...] (757 aa)
COL1A1Collagen alpha-1(I) chain; Type I collagen is a member of group I collagen (fibrillar forming collagen). (1464 aa)
AGXT2Alanine--glyoxylate aminotransferase 2, mitochondrial; Can metabolize asymmetric dimethylarginine (ADMA) via transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and this activity provides mechanism through which the kidney regulates blood pressure; Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family. (514 aa)
BMP4Bone morphogenetic protein 4; Induces cartilage and bone formation. Also acts in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (408 aa)
SOX9Transcription factor SOX-9; Transcriptional regulator that plays a role in chondrocytes differentiation and skeletal development. Binds to the COL2A1 promoter and activates COL2A1 expression, as part of a complex with ZNF219 (By similarity). (509 aa)
TPH1Tryptophan hydroxylase 1; Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. (444 aa)
ADAMTS2A disintegrin and metalloproteinase with thrombospondin motifs 2; Cleaves the propeptides of type I and II collagen prior to fibril assembly (By similarity). Does not act on type III collagen (By similarity). Cleaves lysyl oxidase LOX at a site downstream of its propeptide cleavage site to produce a short LOX form with reduced collagen-binding activity. (1211 aa)
CHADChondroadherin; Promotes attachment of chondrocytes, fibroblasts, and osteoblasts. This binding is mediated (at least for chondrocytes and fibroblasts) by the integrin alpha(2)beta(1). May play an important role in the regulation of chondrocyte growth and proliferation (By similarity); Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily. (359 aa)
SMAD2Mothers against decapentaplegic homolog 2; Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. (467 aa)
TIMP2Metalloproteinase inhibitor 2; Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. Belongs to the protease inhibitor I35 (TIMP) family. (220 aa)
MAPK3Mitogen-activated protein kinase 3; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (379 aa)
NID1Nidogen-1; Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin. Also binds to collagen IV and perlecan. It probably has a role in cell-extracellular matrix interactions. (1247 aa)
VCANVersican core protein; May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid. (3396 aa)
LUMLumican; Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily. (338 aa)
KERAKeratocan; May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix. (352 aa)
RENRenin; Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. (406 aa)
HAPLN1Hyaluronan and proteoglycan link protein 1; Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix. (354 aa)
ADAMTS19ADAM metallopeptidase with thrombospondin type 1 motif 19. (1213 aa)
BMP6Bone morphogenetic protein 6; Induces cartilage and bone formation. (513 aa)
ADAMTS5A disintegrin and metalloproteinase with thrombospondin motifs 5; Metalloproteinase that plays an important role in connective tissue organization, development, inflammation, arthritis, and cell migration. ADAMTS5 is an extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including aggrecan, versican, brevican and neurocan. Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle de [...] (930 aa)
MMP16Matrix metalloproteinase-16; Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. Isoform short cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells. Belongs to the peptidase M10A family. (607 aa)
HAS2Hyaluronan synthase 2; Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan. Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development. M [...] (552 aa)
MMP14Matrix metalloproteinase-14; Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiog [...] (582 aa)
DUOX1Dual oxidase 1; Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. (1551 aa)
FBN1Fibrillin-1; [Fibrillin-1]: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues. Fibrillin-1-containing microfibrils provide long-term force bearing structural support. In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin. In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus [...] (2871 aa)
BGNBiglycan; May be involved in collagen fiber assembly. (368 aa)
MT1EMetallothionein; Metallothioneins have a high content of cysteine residues that bind various heavy metals. (127 aa)
ELNElastin; Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle (By similarity). (786 aa)
SMURF1E3 ubiquitin-protein ligase SMURF1; E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS. Plays a role in dendrite formation by melanocytes. (757 aa)
CCN2CCN family member 2; Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes. Mediates heparin- and divalent cation-dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells. Enhances fibroblast growth factor- induced DNA synthesis; Belongs to the CCN family. (349 aa)
ADAMTS4A disintegrin and metalloproteinase with thrombospondin motifs 4; Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site. (837 aa)
MMP967 kDa matrix metalloproteinase-9; May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide. Belongs to the peptidase M10A family. (707 aa)
ENGEndoglin; Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis. Required for normal structure and integrity of adult vasculature. Regulates the migration of vascular endothelial cells. Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins [...] (658 aa)
BMP2Bone morphogenetic protein 2; Induces cartilage and bone formation. Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. In addition stimulates TMEM119, which upregulates the expression of ATF4 ; Belongs to the TGF-beta family. (396 aa)
EDN1Big endothelin-1; Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells. Belongs to the endothelin/sarafotoxin family. (212 aa)
ADAMTS6ADAM metallopeptidase with thrombospondin type 1 motif 6. (1117 aa)
DUOX2Dual oxidase 2; Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. (1548 aa)
LAMA1Laminin subunit alpha-1; Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. (3075 aa)
ACANAggrecan core protein 2; This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. (2530 aa)
CD44CD44 antigen; Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment. Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection. Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its c [...] (742 aa)
TNFTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 aa)
LAMA2Laminin subunit alpha-2; Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. (3122 aa)
SOD2-2Superoxide dismutase; Destroys radicals which are normally produced within the cells and which are toxic to biological systems. Belongs to the iron/manganese superoxide dismutase family. (176 aa)
PECAM1Platelet endothelial cell adhesion molecule; Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions. Heterophilic interaction with CD177 plays a role in transendothelial migration of neutr [...] (738 aa)
MMP12Macrophage metalloelastase; May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3; Belongs to the peptidase M10A family. (470 aa)
CDH5Cadherin-5; Cadherins are calcium-dependent cell adhesion proteins (By similarity). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions (By similarity). It associates with alpha-catenin forming a link to the cytoskeleton. Acts in concert with KRIT1 and MPP5 to establish and maintain correct endothelial cell polarity and vascular lu [...] (784 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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