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CHRD CHRD AMH AMH BMP4 BMP4 AMHR2 AMHR2 SMAD7 SMAD7 SMAD2 SMAD2 SMURF2 SMURF2 GDF7 GDF7 BMP6 BMP6 GDF6 GDF6 SMAD6 SMAD6 NBL1 NBL1 BMP10 BMP10 SMAD1 SMAD1 LEMD3 LEMD3 GREM2 GREM2 BMP8A BMP8A NOG NOG SMAD3 SMAD3 SMAD4 SMAD4 SMURF1 SMURF1 BMPR1A BMPR1A BMP8B BMP8B ENG ENG GDF5 GDF5 BMPR2 BMPR2 SKI SKI BMP2 BMP2 SMAD9 SMAD9 ACVRL1 ACVRL1 BMP7 BMP7 NEDD4L NEDD4L BMPR1B BMPR1B ACVR1 ACVR1 SKIL SKIL PAEP PAEP SMAD5 SMAD5 TGFBR1 TGFBR1 RNF111 RNF111 GDF2 GDF2 BMPER BMPER GREM1 GREM1
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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
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a 3D structure is known or predicted
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experimentally determined
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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. (955 aa)
AMHMuellerian-inhibiting factor; This glycoprotein, produced by the Sertoli cells of the testis, causes regression of the Muellerian duct. It is also able to inhibit the growth of tumors derived from tissues of Muellerian duct origin. (560 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)
AMHR2Anti-Muellerian hormone type-2 receptor; 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 anti-Muellerian hormone; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (573 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)
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)
SMURF2E3 ubiquitin-protein ligase SMURF2; E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as [...] (748 aa)
GDF7Growth/differentiation factor 7; May play an active role in the motor area of the primate neocortex. (450 aa)
BMP6Bone morphogenetic protein 6; Induces cartilage and bone formation. (513 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 [...] (455 aa)
SMAD6Mothers against decapentaplegic homolog 6; Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF- kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor- activated SMAD1-binding. Binds to regulatory elements in target promoter regions. (496 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. (216 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. (424 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). 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. Belongs to the dwarfin/SMAD family. (465 aa)
LEMD3Inner nuclear membrane protein Man1; Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. (911 aa)
GREM2Gremlin-2; Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells. (168 aa)
BMP8ABone morphogenetic protein 8A; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity). Signaling protein involved in regulation of thermogenesis and energy balance. Proposed to increase the peripheral response of brown adipose tissue (BAT) to adrenergic stimulation while acting centrally in the hypothalamus to increase sympathetic output to BAT. (402 aa)
NOGNoggin; Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite. Essential for cartilage morphogenesis and joint formation. Inhibits chondrocyte differentiation through its interaction with GDF5 and, probably, GDF6. (232 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)
SMAD4Mothers against decapentaplegic homolog 4; In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac- specific gene expression. Binds to SMAD binding elements (SBEs) (5'- GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By [...] (552 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)
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. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (532 aa)
BMP8BBone morphogenetic protein 8B; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity); Belongs to the TGF-beta family. (402 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)
GDF5Growth/differentiation factor 5; Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction. Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG. Required to prevent excessive muscle loss upo [...] (501 aa)
BMPR2Bone morphogenetic protein receptor type-2; 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. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. (1038 aa)
SKISki oncogene; May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Functions as a repressor of TGF-beta signaling. Belongs to the SKI family. (728 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)
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); Belongs to the dwarfin/SMAD family. (467 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. (503 aa)
BMP7Bone morphogenetic protein 7; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis. (431 aa)
NEDD4LE3 ubiquitin-protein ligase NEDD4-like; E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF- beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5. Promotes ubiquitination and [...] (975 aa)
BMPR1BBone morphogenetic protein receptor type-1B; 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 BMP7/OP-1 and GDF5. Positively regulates chondrocyte differentiation through GDF5 interaction. (532 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); Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (509 aa)
SKILSki-like protein; May have regulatory role in cell division or differentiation in response to extracellular signals; Belongs to the SKI family. (684 aa)
PAEPGlycodelin; Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tissues that differ in glycosylation and biological activity. Glycodelin-A has contraceptive and immunosuppressive activities. Glycodelin-C stimulates binding of spermatozoa to the zona pellucida. Glycodelin-F inhibits spermatozoa-zona pellucida binding and significantly suppresses progesterone-induced acrosome reaction of spermatozoa. Glycodelin-S in seminal plasma maintains the u [...] (180 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). (465 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 [...] (507 aa)
RNF111E3 ubiquitin-protein ligase Arkadia; E3 ubiquitin-protein ligase. Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP. In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and [...] (1003 aa)
GDF2Growth/differentiation factor 2; Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. (429 aa)
BMPERBMP-binding endothelial regulator protein; Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes. (685 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). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity). Belongs to the DAN family. (184 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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