Entry Name Melanogenesis - Loxodonta africana (African savanna elephant)
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 Organism Loxodonta africana (African savanna elephant) [GN:
lav ]
Gene 100653565 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
100653927 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
100656672 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634 ]
100657649 DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353 ]
100657749 DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353 ]
100658419 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534 ]
100663321 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
100663829 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100666211 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
100666344 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
100667957 GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
100668533 MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455 ]
100668575 PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
100670218 TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506 ] [EC:1.14.18.-]
100670234 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
100670574 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
100670617 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858 ] [EC:3.1.4.11 ]
100672435 PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
100673586 DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353 ]
100673694 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
100675162 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
100677344 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
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
