Entry Name Melanogenesis - Pongo abelii (Sumatran orangutan)
Description Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism.
Class Organismal Systems; Endocrine systemBRITE hierarchy
Pathway map Ortholog table Organism Pongo abelii (Sumatran orangutan) [GN:
pon ]
Gene 100442753 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X3 [KO:K04632 ]
100294619 CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870 ]
100432292 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
100436186 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
100438869 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
100127093 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
100441756 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
100172074 MITF; microphthalmia-associated transcription factor isoform X3 [KO:K09455 ]
100454626 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
100458686 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
100448038 DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353 ]
100454488 DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353 ]
100454011 DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353 ]
100460406 TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506 ] [EC:1.14.18.-]
100456074 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
100172679 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
100458137 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
100458716 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100460060 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100434502 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100461961 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100451658 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
100433531 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
100462386 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
100436747 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Slominski A, Tobin DJ, Shibahara S, Wortsman J.
Title Melanin pigmentation in mammalian skin and its hormonal regulation.
Journal Reference Authors Busca R, Ballotti R.
Title Cyclic AMP a key messenger in the regulation of skin pigmentation.
Journal Reference Authors Imokawa G.
Title Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
Journal Reference Authors Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A.
Title New aspects on the melanocortins and their receptors.
Journal Reference Authors Chin L.
Title The genetics of malignant melanoma: lessons from mouse and man.
Journal Reference Authors Miller AJ, Mihm MC Jr.
Title Melanoma.
Journal Reference Authors Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
Title Microphthalmia-associated transcription factor in the Wnt signaling pathway.
Journal Reference Authors Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y.
Title The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
Journal Reference Authors Park HY, Gilchrest BA.
Title Signaling pathways mediating melanogenesis.
Journal Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference Authors Park HY, Perez JM, Laursen R, Hara M, Gilchrest BA.
Title Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain.
Journal Reference Authors Sturm RA, Teasdale RD, Box NF.
Title Human pigmentation genes: identification, structure and consequences of polymorphic variation.
Journal Reference Authors Hearing VJ.
Title The melanosome: the perfect model for cellular responses to the environment.
Journal Reference Authors Molina DM, Grewal S, Bardwell L.
Title Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.
Journal Related KO pathway LinkDB All DBs
