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STRINGSTRING
MEN1 MEN1 E2F5 E2F5 SP1 SP1 CTBP1 CTBP1 RBBP4 RBBP4 CREBBP CREBBP HDAC1 HDAC1 PARP1 PARP1 SAP18 SAP18 SKIL SKIL TP53 TP53 SMAD4 SMAD4 TGIF1 TGIF1 SMAD3 SMAD3 UBC UBC SMAD2 SMAD2 EP300 EP300 TRIM33 TRIM33 SKI SKI FOXO1 FOXO1 FOXH1 FOXH1 UBB UBB ZFYVE9 ZFYVE9 TGFBR1 TGFBR1 ERBB2IP ERBB2IP GPC1 GPC1
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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small protein node
small nodes:
protein of unknown 3D structure
large protein node
large nodes:
some 3D structure is known or predicted
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colored protein node
colored nodes:
query proteins and first shell of interactors
non-colored protein node
white nodes:
second shell of interactors
Edges:
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
database edge
from curated databases
experiment edge
experimentally determined
Predicted Interactions
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gene neighborhood
fusion edge
gene fusions
cooccurrence edge
gene co-occurrence
Others
textmining edge
textmining
coexpression edge
co-expression
homology edge
protein homology
Your Input:
SKILSKI-like oncogene; May have regulatory role in cell division or differentiation in response to extracellular signals (684 aa)
SMAD2SMAD family member 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)
CREBBPCREB binding protein; Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (2442 aa)
EP300E1A binding protein p300; Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates ’Lys-131’ of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and [...] (2414 aa)
GPC1glypican 1; Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-med [...] (558 aa)
TP53tumor protein p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (By similarity) (393 aa)
ZFYVE9zinc finger, FYVE domain containing 9; Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization (1425 aa)
CTBP1C-terminal binding protein 1; Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation. Corepressor targeting diverse transcription regulators such as GLIS2. Has dehydrogenase activity (440 aa)
UBBubiquitin B (229 aa)
TGIF1TGFB-induced factor homeobox 1; Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII- RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha [...] (401 aa)
SP1Sp1 transcription factor; Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR- alpha G-box promoter. May have a role in modulating the cellular response to DNA d [...] (785 aa)
SMAD3SMAD family member 3 (425 aa)
MEN1multiple endocrine neoplasia I (615 aa)
SMAD4SMAD family member 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 syngernistic transcriptional activity in response to TGF-beta. [...] (552 aa)
UBCubiquitin C (685 aa)
TRIM33tripartite motif containing 33; Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed-16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as a [...] (1127 aa)
PARP1poly (ADP-ribose) polymerase 1; Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP- ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a [...] (1014 aa)
RBBP4retinoblastoma binding protein 4; Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome [...] (425 aa)
HDAC1histone deacetylase 1; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST- mediated transcription in resting neurons. Upon calcium s [...] (482 aa)
TGFBR1transforming growth factor, beta receptor 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, immunosuppres [...] (503 aa)
FOXH1forkhead box H1; Transcriptional activator. Recognizes and binds to the DNA sequence 5’-TGT[GT][GT]ATT-3’. Required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. Forms a transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site on the GSC promoter called TARE (TGF-beta/activin response element) (365 aa)
SKIv-ski sarcoma viral oncogene homolog (avian); 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 (728 aa)
FOXO1forkhead box O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5’-TT[G/A]TTTTG-3’ and the related Daf-16 family binding element (DBE) with consensus sequence 5’- TT[G/A]TTTAC-3’. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts syngernistically with ATF4 to suppress osteocalcin/BGL [...] (655 aa)
ERBB2IPerbb2 interacting protein (1371 aa)
SAP18Sin3A-associated protein, 18kDa; Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent [...] (172 aa)
E2F5E2F transcription factor 5, p130-binding; Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation. May mediate growth factor- initiated signal transduction. It is likely involved in the early responses of resting cells to growth factor stimulation (346 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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