STRINGSTRING
CD4 CD4 LAG3 LAG3 NFKBIA NFKBIA NDC80 NDC80 COMMD9 COMMD9 PIK3CA PIK3CA COMMD4 COMMD4 COMMD10 COMMD10 EGFR EGFR COMMD7 COMMD7 SCLT1 SCLT1 REL REL COMMD1 COMMD1 HAVCR2 HAVCR2 CASP9 CASP9 PDCD1 PDCD1 E2F1 E2F1 COMMD6 COMMD6 MTOR MTOR TFDP1 TFDP1 CCDC22 CCDC22 CCDC93 CCDC93 COMMD3 COMMD3 PIK3CD PIK3CD COMMD8 COMMD8 CD274 CD274 SIGLEC15 SIGLEC15 CCK CCK GAPDH GAPDH PDCD1LG2 PDCD1LG2 CD8A CD8A COMMD5 COMMD5 TNF TNF TIGIT TIGIT PIK3CG PIK3CG COMMD2 COMMD2 HIF1A HIF1A AKT1 AKT1 MYC MYC COMMD7-2 COMMD7-2 CTLA4 CTLA4 PIK3CB PIK3CB
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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
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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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experimentally determined
Predicted Interactions
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CD4T-cell surface glycoprotein CD4; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kina [...] (458 aa)
LAG3Secreted lymphocyte activation gene 3 protein; Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells. Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/P [...] (525 aa)
NFKBIANF-kappa-B inhibitor alpha; Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. (317 aa)
NDC80Kinetochore protein NDC80 homolog; Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spind [...] (642 aa)
COMMD9COMM domain-containing protein 9; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride- sensitive sodium channel (ENaC) subunits. (198 aa)
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to v [...] (1068 aa)
COMMD4COMM domain-containing protein 4; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF- kappa-B. (199 aa)
COMMD10COMM domain-containing protein 10; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (202 aa)
EGFREpidermal growth factor receptor; Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin- binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at leas [...] (1210 aa)
COMMD7COMM domain-containing protein 7; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Associates with the NF-kappa-B complex and suppresses its transcriptional activity. (200 aa)
SCLT1Sodium channel and clathrin linker 1; Adapter protein that links SCN10A to clathrin. Regulates SCN10A channel activity, possibly by promoting channel internalization (By similarity). (688 aa)
RELProto-oncogene c-Rel; Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferen [...] (619 aa)
COMMD1COMM domain-containing protein 1; Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2. Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Involved in the regulation of membrane expression and ubiquitin [...] (190 aa)
HAVCR2Hepatitis A virus cellular receptor 2; Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand. Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss [...] (301 aa)
CASP9Caspase-9 subunit p10; Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP); Belongs to the peptidase C14A family. (416 aa)
PDCD1Programmed cell death protein 1; Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self. Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the pr [...] (288 aa)
E2F1Transcription factor E2F1; Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA bindi [...] (437 aa)
COMMD6COMM domain-containing protein 6; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF- kappa-B. Inhibits TNF-induced NFKB1 activation. (98 aa)
MTORSerine/threonine-protein kinase mTOR; Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF [...] (2549 aa)
TFDP1Transcription factor Dp-1; Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters ; Belongs to the E2F/DP family. (410 aa)
CCDC22Coiled-coil domain-containing protein 22; Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF-kappa-B activity via association with COMMD1 and involving a CUL2-dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10. Component of the CCC complex, which is inv [...] (627 aa)
CCDC93Coiled-coil domain-containing protein 93; Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and coop [...] (631 aa)
COMMD3COMM domain-containing protein 3; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride- sensitive sodium channel (ENaC) subunits. (195 aa)
PIK3CDPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell recepto [...] (1044 aa)
COMMD8COMM domain-containing protein 8; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (183 aa)
CD274Programmed cell death 1 ligand 1; Plays a critical role in induction and maintenance of immune tolerance to self. As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response. Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10). (290 aa)
SIGLEC15Sialic acid-binding Ig-like lectin 15; Binds sialylated glycoproteins. (328 aa)
CCKCholecystokinin-58 desnonopeptide; This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion. (115 aa)
GAPDHGlyceraldehyde-3-phosphate dehydrogenase; Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations throu [...] (335 aa)
PDCD1LG2Programmed cell death 1 ligand 2; Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle progression and cytokine production (By similarity). (273 aa)
CD8AT-cell surface glycoprotein CD8 alpha chain; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Sr [...] (235 aa)
COMMD5COMM domain-containing protein 5; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Negatively regulates cell proliferation. Negatively regulates cell cycle G2/M phase transition probably by transactivating p21/CDKN1A through the p53/TP53-independent signaling pathway. Involved in kidney proximal tubule morphogenesis (By similarity). Down-regulates activation of NF-kappa-B. (224 aa)
TNFTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 aa)
TIGITT-cell immunoreceptor with Ig and ITIM domains; Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. (244 aa)
PIK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates [...] (1102 aa)
COMMD2COMM domain-containing protein 2; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (199 aa)
HIF1AHypoxia-inducible factor 1-alpha; Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequenc [...] (850 aa)
AKT1RAC-alpha serine/threonine-protein kinase; AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the [...] (480 aa)
MYCMyc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). (454 aa)
COMMD7-2COMM domain-containing protein 7. (272 aa)
CTLA4Cytotoxic T-lymphocyte protein 4; Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28. (223 aa)
PIK3CBPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation [...] (1070 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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