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  • 11.0 [archived version]
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RPAP1 RPAP1 CBL CBL SMAD7 SMAD7 SMAD1 SMAD1 DST DST ITGB4 ITGB4 SMAD2 SMAD2 ERBB2 ERBB2 SMAD3 SMAD3 SMAD4 SMAD4 RAF1 RAF1 HRAS HRAS NOD2 NOD2 ERBB2IP ERBB2IP CHUK CHUK SHOC2 SHOC2 BTRC BTRC DLG4 DLG4 LPHN2 LPHN2 LPHN1 LPHN1 TRIM41 TRIM41 LPHN3 LPHN3 LRRC1 LRRC1 PKP4 PKP4 CTNND2 CTNND2 PDZD2 PDZD2
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
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
some 3D structure is known or predicted
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
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
ITGB4Integrin beta-4; Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6-ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGA6-ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (1822 aa)
RAF1RAF proto-oncogene serine/threonine-protein kinase; Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kina [...] (648 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)
CBLE3 ubiquitin-protein ligase CBL; Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family [...] (906 aa)
ERBB2Receptor tyrosine-protein kinase erbB-2; Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and [...] (1255 aa)
NOD2Nucleotide-binding oligomerization domain-containing protein 2; Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macroph [...] (1040 aa)
RPAP1RNA polymerase II-associated protein 1; Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3 (1393 aa)
CTNND2Catenin delta-2; Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses. Involved in the regulation of Wnt signaling. It probably acts on beta- catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules (1225 aa)
DSTDystonin; Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin- containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two- dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for [...] (5537 aa)
TRIM41E3 ubiquitin-protein ligase TRIM41; Functions as an E3 ligase that catalyzes the ubiquitin- mediated degradation of protein kinase C; Ring finger proteins (630 aa)
LPHN2Adhesion G protein-coupled receptor L2; Calcium-independent receptor of low affinity for alpha- latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis; Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily (1403 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)
LPHN1Adhesion G protein-coupled receptor L1; Calcium-independent receptor of high affinity for alpha- latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Receptor probably implicated in the regulation of exocytosis (By similarity) (1474 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)
SHOC2Leucine-rich repeat protein SHOC-2; Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the ’Ser-259’ inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes (582 aa)
BTRCF-box/WD repeat-containing protein 1A; Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling. SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. Ubiquitination of NFKBIA occurs at ’Lys- 21 [...] (605 aa)
CHUKInhibitor of nuclear factor kappa-B kinase subunit alpha; Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into [...] (745 aa)
LRRC1Leucine-rich repeat-containing protein 1; Leucine rich repeat containing 1 (524 aa)
PKP4Plakophilin-4; Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques; Armadillo repeat containing (1192 aa)
DLG4Disks large homolog 4; Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B (By similarity); Belongs to the MAGUK family (767 aa)
PDZD2PDZ domain containing 2 (2839 aa)
HRASGTPase HRas; Involved in the activation of Ras protein signal transduction. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity; Belongs to the small GTPase superfamily. Ras family (189 aa)
LPHN3Adhesion G protein-coupled receptor L3; Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells. Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex; Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily (1469 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)
ERBB2IPErbin; Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated ’Tyr-1248’ of receptor ERBB2, it may contribute to stabilize this unphosphorylated state. Inhibits NOD2-dependent NF-kappa-B signaling and proinflammatory cytokine secretion; Belongs to the LAP (LRR and PDZ) protein family (1419 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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