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ASIP ASIP SERPINF1 SERPINF1 PLCB2 PLCB2 GNA15 GNA15 TYR TYR GNAQ GNAQ ADCY9 ADCY9 ITPR1 ITPR1 PRKACA PRKACA ADCY4 ADCY4 PLCB1 PLCB1 ADCY2 ADCY2 PRKACB PRKACB GNAS GNAS PRKACG PRKACG PLCB4 PLCB4 MLANA MLANA TYRP1 TYRP1 POMC POMC CREB1 CREB1 MITF MITF DCT DCT PMEL PMEL ARRB2 ARRB2 ARRB1 ARRB1 GPR143 GPR143 PLCB3 PLCB3 MC1R MC1R PRKCB PRKCB
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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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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
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gene fusions
gene co-occurrence
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textmining
co-expression
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ASIPAgouti-signaling protein; Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). In higher primates, agouti may affect the quality of hair pigmentation rather than its pattern of deposition. Could well play a role in neuroendocrine aspects of melanocortin action. May have some functional role in regulating the lipid metabolism with adipocytes. (132 aa)
SERPINF1Pigment epithelium-derived factor; Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. (418 aa)
PLCB21-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. (1185 aa)
GNA15Guanine nucleotide-binding protein subunit alpha-15; Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. (374 aa)
TYRTyrosinase; This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone. Belongs to the tyrosinase family. (529 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. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM- derived neutrophils and dendritic cells (in vitro) (By similarity). Belongs to the G-alpha family. G(q) subfamily. (359 aa)
ADCY9Adenylate cyclase type 9; Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors. Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors. (1353 aa)
ITPR1Inositol 1,4,5-trisphosphate receptor type 1; Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (By similarity). Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways (By similarity). (2743 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)
ADCY4Adenylate cyclase type 4; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1077 aa)
PLCB11-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. (1216 aa)
ADCY2Adenylate cyclase type 2; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity). Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. (1091 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 [...] (398 aa)
GNASGuanine nucleotide-binding protein G(s) subunit alpha isoforms XLas; Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein- coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as GNAS isoforms (By similarity). (1037 aa)
PRKACGcAMP-dependent protein kinase catalytic subunit gamma; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. (351 aa)
PLCB41-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. This form has a role in retina signal transduction. (1194 aa)
MLANAMelanoma antigen recognized by T-cells 1; Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes. (118 aa)
TYRP15,6-dihydroxyindole-2-carboxylic acid oxidase; Plays a role in melanin biosynthesis. Catalyzes the oxidation of 5,6-dihydroxyindole-2- carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu(2+) ions, but not in the presence of Zn(2+). May regulate or influence the type of melanin synthesized. Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (By similarity). (537 aa)
POMCCorticotropin-like intermediary peptide; [Corticotropin]: Stimulates the adrenal glands to release cortisol. [Melanocyte-stimulating hormone beta]: Increases the pigmentation of skin by increasing melanin production in melanocytes. [Met-enkephalin]: Endogenous opiate; Belongs to the POMC family. (267 aa)
CREB1Cyclic AMP-responsive element-binding protein 1; Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells; Belongs to the bZIP family. (341 aa)
MITFMicrophthalmia-associated transcription factor; Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocyt [...] (526 aa)
DCTL-dopachrome tautomerase; Catalyzes the conversion of L-dopachrome into 5,6- dihydroxyindole-2-carboxylic acid (DHICA). Involved in regulating eumelanin and phaeomelanin levels. Belongs to the tyrosinase family. (552 aa)
PMELMelanocyte protein PMEL; Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity. (668 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 [...] (430 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)
GPR143G-protein coupled receptor 143; Receptor for tyrosine, L-DOPA and dopamine. After binding to L-DOPA, stimulates Ca(2+) influx into the cytoplasm, increases secretion of the neurotrophic factor SERPINF1 and relocalizes beta arrestin at the plasma membrane; this ligand-dependent signaling occurs through a G(q)-mediated pathway in melanocytic cells. Its activity is mediated by G proteins which activate the phosphoinositide signaling pathway. Plays also a role as an intracellular G protein-coupled receptor involved in melanosome biogenesis, organization and transport. (404 aa)
PLCB31-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. (1234 aa)
MC1RMelanocyte-stimulating hormone receptor; Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase; Belongs to the G-protein coupled receptor 1 family. (317 aa)
PRKCBProtein kinase C beta type; Calcium-activated, phospholipid- and diacylglycerol (DAG)- dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR- induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser- [...] (673 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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