Entry Name Melanogenesis - Mus musculus (house mouse)
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 Mus musculus (house mouse) [GN:
mmu ]
Gene 12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
13542 Dvl1; dishevelled segment polarity protein 1 [KO:K02353 ]
13543 Dvl2; dishevelled segment polarity protein 2 [KO:K02353 ]
13544 Dvl3; dishevelled segment polarity protein 3 [KO:K02353 ]
14681 Gnao1; guanine nucleotide binding protein, alpha O [KO:K04534 ]
14682 Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
16842 Lef1; lymphoid enhancer binding factor 1 [KO:K04492 ]
17342 Mitf; melanogenesis associated transcription factor [KO:K09455 ]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048 ]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048 ]
20890 Wnt8a; wingless-type MMTV integration site family, member 8A [KO:K00714 ]
21414 Tcf7; transcription factor 7, T cell specific [KO:K02620 ]
21415 Tcf7l1; transcription factor 7 like 1 (T cell specific, HMG box) [KO:K04490 ]
21416 Tcf7l2; transcription factor 7 like 2, T cell specific, HMG box [KO:K04491 ]
216795 Wnt9a; wingless-type MMTV integration site family, member 9A [KO:K01064 ]
22178 Tyrp1; tyrosinase-related protein 1 [KO:K00506 ] [EC:1.14.18.-]
22408 Wnt1; wingless-type MMTV integration site family, member 1 [KO:K03209 ]
22409 Wnt10a; wingless-type MMTV integration site family, member 10A [KO:K01357 ]
22410 Wnt10b; wingless-type MMTV integration site family, member 10B [KO:K01357 ]
22411 Wnt11; wingless-type MMTV integration site family, member 11 [KO:K01384 ]
22412 Wnt9b; wingless-type MMTV integration site family, member 9B [KO:K01064 ]
22413 Wnt2; wingless-type MMTV integration site family, member 2 [KO:K00182 ]
22414 Wnt2b; wingless-type MMTV integration site family, member 2B [KO:K00182 ]
22415 Wnt3; wingless-type MMTV integration site family, member 3 [KO:K00312 ]
22416 Wnt3a; wingless-type MMTV integration site family, member 3A [KO:K00312 ]
22417 Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408 ]
22418 Wnt5a; wingless-type MMTV integration site family, member 5A [KO:K00444 ]
22419 Wnt5b; wingless-type MMTV integration site family, member 5B [KO:K00444 ]
22420 Wnt6; wingless-type MMTV integration site family, member 6 [KO:K00445 ]
22421 Wnt7a; wingless-type MMTV integration site family, member 7A [KO:K00572 ]
22422 Wnt7b; wingless-type MMTV integration site family, member 7B [KO:K00572 ]
22423 Wnt8b; wingless-type MMTV integration site family, member 8B [KO:K00714 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048 ]
93735 Wnt16; wingless-type MMTV integration site family, member 16 [KO:K01558 ]
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
