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RNF165 RNF165 MAP3K7 MAP3K7 SMAD6 SMAD6 SMAD9 SMAD9 SMAD1 SMAD1 ING2 ING2 SMAD5 SMAD5 SKI SKI SMAD4 SMAD4 TGFBR1 TGFBR1 SMAD7 SMAD7 SMAD2 SMAD2 SMAD3 SMAD3 SKIL SKIL SMURF2 SMURF2 NCOR1 NCOR1 NEDD4 NEDD4 VPS28 VPS28 RNF111 RNF111 WWP1 WWP1 PML PML ESR1 ESR1 FZR1 FZR1 CDC27 CDC27 CDC16 CDC16 RB1 RB1
Nodes:
Network nodes represent proteins
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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colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
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empty nodes:
proteins of unknown 3D structure
filled nodes:
some 3D structure is known or predicted
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Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
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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)
RB1Retinoblastoma-associated protein; Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransfer [...] (928 aa)
PMLProtein PML; Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression- activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respe [...] (882 aa)
NCOR1Nuclear receptor corepressor 1; Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6 (2440 aa)
RNF165E3 ubiquitin-protein ligase RNF165; E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL; Belongs to the Arkadia family (346 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)
ING2Inhibitor of growth protein 2; Seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53. Component of a mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity seems to be modulated by binding to phosphoinositides (PtdInsPs); Belongs to the ING family (280 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 mi [...] (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 s [...] (552 aa)
CDC16Cell division cycle protein 16 homolog; Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins- it mainly mediates the formation of ’Lys-11’-linked polyubiquitin chains and, to a lower extent, the formation of ’Lys-48’- and ’Lys-63’-linked polyubiquitin chains; Belongs to the APC6/CDC16 family (620 aa)
MAP3K7Mitogen-activated protein kinase kinase kinase 7; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as a [...] (606 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 carcinogen [...] (503 aa)
VPS28Vacuolar protein sorting-associated protein 28 homolog; Component of the ESCRT-I complex, a regulator of vesicular trafficking process (233 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)
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)
FZR1Fizzy-related protein homolog; Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint- its dephosphorylation and [...] (496 aa)
ESR1Estrogen receptor; Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA- binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial a [...] (595 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)
NEDD4E3 ubiquitin-protein ligase NEDD4; 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. Specifically ubiquitinates ’Lys-63’ in target proteins. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. [...] (1319 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)
WWP1NEDD4-like E3 ubiquitin-protein ligase WWP1; 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. Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response to [...] (922 aa)
CDC27Cell division cycle protein 27 homolog; Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins- it mainly mediates the formation of ’Lys-11’-linked polyubiquitin chains and, to a lower extent, the formation of ’Lys-48’- and ’Lys-63’-linked polyubiquitin chains (830 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)
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 [...] (995 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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