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Sphk1 Sphk1 Git1 Git1 Igf1 Igf1 Smad2 Smad2 LOC103694380 LOC103694380 Egfr Egfr Hdac6 Hdac6 Tac1 Tac1 Ptger4 Ptger4 Rala Rala Cxcr2 Cxcr2 Gnaq Gnaq Igf1r Igf1r Agt Agt Grk1 Grk1 Cxcr4 Cxcr4 Grk2 Grk2 Arrb2 Arrb2 Egr1 Egr1 Sphk2 Sphk2 Csf2 Csf2 Adm Adm Akt1 Akt1 Prkaca Prkaca Arrb1 Arrb1 Ezr Ezr Insr Insr Cxcl12 Cxcl12 Pdgfrb Pdgfrb Prkacb Prkacb Hdac6-2 Hdac6-2 Mdm2 Mdm2 Mapk3 Mapk3 Ccr5 Ccr5
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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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from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
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Sphk1Sphingosine kinase 1; Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (Probable). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (By similarity). Involved in the regulation of inflammatory response [...] (458 aa)
Git1ARF GTPase-activating protein GIT1; GTPase-activating protein for the ADP ribosylation factor family. May serve as a scaffold to bring together molecules to form signaling modules controlling vesicle trafficking, adhesion and cytoskeletal organization. Increases the speed of cell migration, as well as the size and rate of formation of protrusions, possibly by targeting PAK1 to adhesions and the leading edge of lamellipodia. Sequesters inactive non-tyrosine-phosphorylated paxillin in cytoplasmic complexes. Involved in the regulation of cytokinesis; the function may involve ENTR1 and PTP [...] (752 aa)
Igf1Insulin-like growth factor I; The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]- 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exo [...] (159 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)
LOC103694380Tumor 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 (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (235 aa)
EgfrReceptor protein-tyrosine kinase. (1209 aa)
Hdac6Histone deacetylase 6. (1152 aa)
Tac1C-terminal-flanking peptide; Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles; Belongs to the tachykinin family. (130 aa)
Ptger4Prostaglandin E2 receptor EP4 subtype; Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function; Belongs to the G-protein coupled receptor 1 family. (488 aa)
RalaRas-related protein Ral-A; Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells (By similarity). Th [...] (206 aa)
Cxcr2C-X-C chemokine receptor type 2; Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2 (By similarity). (359 aa)
GnaqGuanine nucleotide-binding protein G(q) subunit alpha; Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. (359 aa)
Igf1rInsulin-like growth factor 1 receptor alpha chain; Receptor tyrosine kinase which mediates actions of insulin- like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates ( [...] (1367 aa)
AgtAngiotensin 1-4; Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis. [Angiotensin-3]: stimulates aldosterone release. Belongs to the serpin family. (477 aa)
Grk1Rhodopsin kinase GRK1; Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade (By similarity). This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). May play a role in the maintenance of the outer nuclear layer in the retina (By similarity). (564 aa)
Cxcr4C-X-C chemokine receptor type 4; Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By similarity). Plays a role in regulation of cell migration, e.g. during wound healing. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS- induced inflammatory response, including TNF secretion by monocytes (By similarity). Inv [...] (349 aa)
Grk2Beta-adrenergic receptor kinase 1; Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation- independent manner. Positively regulates ciliary smoothened (SMO)- dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity. Belongs to the protei [...] (652 aa)
Arrb2Beta-arrestin-2; Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta- arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin- associated sorting proteins) and re [...] (410 aa)
Egr1Early growth response protein 1; Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps pre [...] (536 aa)
Sphk2RCG53912, isoform CRA_a. (616 aa)
Csf2Granulocyte-macrophage colony-stimulating factor; Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. (144 aa)
AdmProadrenomedullin N-20 terminal peptide; AM and PAMP are potent hypotensive and vasodilatator agents. (185 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)
PrkacacAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 aa)
Arrb1Beta-arrestin-1; Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta- arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin- associated sorting proteins) and re [...] (418 aa)
EzrEzrin; Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis (By similarity). (586 aa)
InsrInsulin receptor subunit alpha; Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lea [...] (1384 aa)
Cxcl12Stromal cell-derived factor-1 gamma; Belongs to the intercrine alpha (chemokine CxC) family. (119 aa)
PdgfrbPlatelet-derived growth factor receptor beta; Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at v [...] (1097 aa)
PrkacbcAMP-dependent protein kinase catalytic subunit beta; Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subu [...] (351 aa)
Hdac6-2Histone deacetylase 6. (1155 aa)
Mdm2E3 ubiquitin-protein ligase Mdm2; Belongs to the MDM2/MDM4 family. (483 aa)
Mapk3Mitogen-activated protein kinase 3; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (380 aa)
Ccr5C-C chemokine receptor type 5; Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation (By similarity). (354 aa)
Your Current Organism:
Rattus norvegicus
NCBI taxonomy Id: 10116
Other names: Buffalo rat, Norway rat, R. norvegicus, Rattus PC12 clone IS, Rattus sp. strain Wistar, Sprague-Dawley rat, Wistar rats, brown rat, laboratory rat, rat, rats, zitter rats
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