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Smad9 Smad9 Chrd Chrd Tgfbr3 Tgfbr3 Tgfb2 Tgfb2 Fmod Fmod Grem2 Grem2 Dcn Dcn Acvr2a Acvr2a Gdf7 Gdf7 Acvr1b Acvr1b Tgfbr1 Tgfbr1 Gdf11 Gdf11 Inhbe Inhbe Inhbc Inhbc Gdf6 Gdf6 Smad6 Smad6 Bmp10 Bmp10 Bmp4 Bmp4 Tgfb3 Tgfb3 Bmp5 Bmp5 Fst Fst Smad5 Smad5 Bmp6 Bmp6 Inhba Inhba Acvr2b Acvr2b Smurf2 Smurf2 Ccn2 Ccn2 Bmpr1b Bmpr1b Smad7 Smad7 Smad1 Smad1 Inha Inha Tgfb1 Tgfb1 Ltbp3 Ltbp3 Ltbp4 Ltbp4 Bmp2 Bmp2 Nog Nog Tgfbr2 Tgfbr2 Grem1 Grem1 Zfyve9 Zfyve9 Bmpr2 Bmpr2 Smad3 Smad3 Mstn Mstn Ltbp1 Ltbp1 Bmp8b Bmp8b Bmp8a Bmp8a Gdf3 Gdf3 Acvr1c Acvr1c Nbl1 Nbl1 LOC103690035 LOC103690035 Gdf5 Gdf5 Eng Eng Smad9-2 Smad9-2 Bmp7 Bmp7 Inhbb Inhbb Ltbp2 Ltbp2 Acvr1 Acvr1 Bgn Bgn Gdf2 Gdf2 Acvrl1 Acvrl1 Zfyve16 Zfyve16 Smurf1 Smurf1 Smad4 Smad4 Bmpr1a Bmpr1a Smad2 Smad2
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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
white nodes:
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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Edges represent protein-protein associations
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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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Smad9Mothers against decapentaplegic homolog 9; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor- regulated SMAD (R-SMAD) (By similarity). Has been shown to be activated by activin type I receptor-like kinase-2 (ALK-2) which stimulates heteromerization between SMAD9 and SMAD4. ALK-2 binds TGF-beta, activin and BMP; Belongs to the dwarfin/SMAD family. (430 aa)
ChrdChordin; Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes (By similarity); Belongs to the chordin family. (948 aa)
Tgfbr3Transforming growth factor beta receptor type 3; Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors. (853 aa)
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 (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transfor [...] (442 aa)
FmodFibromodulin; Affects the rate of fibrils formation. May have a primary role in collagen fibrillogenesis (By similarity); Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily. (376 aa)
Grem2Gremlin. (168 aa)
DcnDecorin; May affect the rate of fibrils formation (By similarity). May be implicated in the dilatation of the rat cervix. (354 aa)
Acvr2aActivin receptor type-2A; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (513 aa)
Gdf7Growth differentiation factor 7. (449 aa)
Acvr1bActivin receptor type-1B; Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine [...] (505 aa)
Tgfbr1TGF-beta receptor type-1; Transmembrane serine/threonine kinase forming with the TGF- beta type II serine/threonine kinase receptor, TGFBR2, the non- promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinog [...] (497 aa)
Gdf11Growth/differentiation factor 11; Secreted signal that acts globally to specify positional identity along the anterior/posterior axis during development. May play critical roles in patterning both mesodermal and neural tissues and in establishing the skeletal pattern. Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3. Belongs to the TGF-beta family. (405 aa)
InhbeInhibin beta E chain; Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. (350 aa)
InhbcInhibin beta C chain; Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. (351 aa)
Gdf6Growth/differentiation factor 6; Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal- ventral positional information in the retina and controls the formation of the retinotectal map. Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regulation of GDF6 expression seems to be a mechanism for evolving species-speci [...] (452 aa)
Smad6Mothers against decapentaplegic homolog. (457 aa)
Bmp10Bone morphogenetic protein 10; Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines. Belongs to the TGF-beta family. (364 aa)
Bmp4Bone morphogenetic protein 4; Induces cartilage and bone formation. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (408 aa)
Tgfb3Transforming growth factor beta-3 proprotein; Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively. Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi appa [...] (412 aa)
Bmp5Bone morphogenetic protein 5. (302 aa)
FstFollistatin; Binds directly to activin and functions as an activin antagonist. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (FSH). (344 aa)
Smad5Mothers against decapentaplegic homolog 5; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor- regulated SMAD (R-SMAD) (By similarity). (465 aa)
Bmp6Bone morphogenetic protein 6; Induces cartilage and bone formation. (506 aa)
InhbaInhibin beta A chain; Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. (424 aa)
Acvr2bActivin receptor type-2B; Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to [...] (512 aa)
Smurf2SMAD-specific E3 ubiquitin protein ligase 2. (637 aa)
Ccn2CCN family member 2; Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes (By similarity). Mediates heparin- and divalent cation- dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells (By similarity). Enhances fibroblast growth factor-induced DNA synthesis (By similarity); Belongs to the CCN family. (347 aa)
Bmpr1bSerine/threonine-protein kinase receptor; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (502 aa)
Smad7Mothers against decapentaplegic homolog 7; Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a [...] (426 aa)
Smad1Mothers against decapentaplegic homolog 1; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor- regulated SMAD (R-SMAD). Has been shown to be also activated by TGF- beta (transforming growth factor) type I receptor kinase in rat intestinal epithelial cells (IEC 4-1). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)- mediated cardiac-specific gene expression (By similarity). (468 aa)
InhaInhibin alpha chain; Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. (366 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)
Ltbp3Latent-transforming growth factor beta-binding protein 3. (1253 aa)
Ltbp4Latent-transforming growth factor beta-binding protein 4. (1631 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. (394 aa)
NogNoggin; Essential for cartilage morphogenesis and joint formation. Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite (By similarity). Inhibits chondrocyte differentiation through its interaction with GDF5 and, probably, GDF6 (By similarity). (232 aa)
Tgfbr2TGF-beta receptor type-2; Transmembrane serine/threonine kinase forming with the TGF- beta type I serine/threonine kinase receptor, TGFBR1, the non- promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinoge [...] (567 aa)
Grem1Gremlin-1; Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (By similarity). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed. (184 aa)
Zfyve9Zinc finger FYVE domain-containing protein. (1398 aa)
Bmpr2Receptor protein serine/threonine kinase; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (1038 aa)
Smad3Mothers against decapentaplegic homolog 3; 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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP- 1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and m [...] (425 aa)
MstnGrowth/differentiation factor 8; Acts specifically as a negative regulator of skeletal muscle growth; Belongs to the TGF-beta family. (376 aa)
Ltbp1Latent-transforming growth factor beta-binding protein 1; Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (By similarity). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (By similarity); Belongs to the LTBP family. (1712 aa)
Bmp8bBone morphogenetic protein 8b. (399 aa)
Bmp8aBone morphogenetic protein 8a. (399 aa)
Gdf3Similar to growth/differentiation factor GDF-3-mouse (Predicted). (366 aa)
Acvr1cActivin receptor type-1C; Serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. Receptor for activin AB, activin B and NODAL. Plays a role in cell differentiation, growth arrest and apoptosis. (493 aa)
Nbl1Neuroblastoma suppressor of tumorigenicity 1; Possible candidate as a tumor suppressor gene of neuroblastoma. May play an important role in preventing cells from entering the final stage (G1/S) of the transformation process; Belongs to the DAN family. (178 aa)
LOC103690035Receptor protein serine/threonine kinase; Belongs to the protein kinase superfamily. (431 aa)
Gdf5Growth differentiation factor 5. (495 aa)
EngEndoglin. (699 aa)
Smad9-2Mothers against decapentaplegic homolog 9. (430 aa)
Bmp7Bone morphogenetic protein 7. (430 aa)
InhbbInhibin beta B chain; Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. (407 aa)
Ltbp2Latent-transforming growth factor beta-binding protein 2; May play an integral structural role in elastic-fiber architectural organization and/or assembly. Belongs to the LTBP family. (1831 aa)
Acvr1Activin receptor type-1; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved for left-right pattern formation during embryogenesis (By similarity). (528 aa)
BgnBiglycan; May be involved in collagen fiber assembly. (369 aa)
Gdf2Similar to Growth/differentiation factor 2 (GDF-2) (Bone morphogenetic protein 9) (BMP-9). (430 aa)
Acvrl1Serine/threonine-protein kinase receptor R3; Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (504 aa)
Zfyve16Zinc finger FYVE-type-containing 16. (1547 aa)
Smurf1E3 ubiquitin-protein ligase. (731 aa)
Smad4Mothers against decapentaplegic homolog 4; Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in r [...] (550 aa)
Bmpr1aBone morphogenetic protein receptor type-1A; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6. (532 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)
Your Current Organism:
Rattus norvegicus
NCBI taxonomy Id: 10116
Other names: Buffalo rat, Norway rat, R. norvegicus, Rattus PC12 clone IS, Rattus sp. strain Wistar, Sprague-Dawley rat, Wistar rats, brown rat, laboratory rat, rat, rats, zitter rats
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