KEGG   PATHWAY: ray04916
ray04916                    Pathway                                

Melanogenesis - Rousettus aegyptiacus (Egyptian rousette)
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.
Organismal Systems; Endocrine system
Pathway map
ray04916  Melanogenesis

Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
107498502  POMC; pro-opiomelanocortin [KO:K05228]
107519502  ASIP; agouti-signaling protein [KO:K08725]
107500068  neuroendocrine secretory protein 55-like [KO:K04632]
107500067  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
107512406  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107502700  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:]
107498506  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:]
107498014  ADCY4; LOW QUALITY PROTEIN: adenylate cyclase type 4 [KO:K08044] [EC:]
107518038  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:]
107514224  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107512248  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
107497689  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107521680  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:]
107519437  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107511590  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107505169  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107509179  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107502779  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107511864  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107510647  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107499057  CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
107519708  LOW QUALITY PROTEIN: histone acetyltransferase p300-like [KO:K04498] [EC:]
107505594  LOW QUALITY PROTEIN: histone acetyltransferase p300-like [KO:K04498] [EC:]
107521673  CREBBP; CREB-binding protein [KO:K04498] [EC:]
107508087  LOW QUALITY PROTEIN: histone acetyltransferase p300-like [KO:K04498] [EC:]
107509178  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
107514294  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107505364  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
107499803  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
107509667  WNT3A; protein Wnt-3a [KO:K00312]
107508173  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107513057  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
107503411  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
107500582  WNT5B; protein Wnt-5b [KO:K00444]
107516780  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
107505517  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
107502411  WNT7A; protein Wnt-7a [KO:K00572]
107518710  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
107499773  WNT8B; protein Wnt-8b [KO:K00714]
107509675  WNT9A; protein Wnt-9a [KO:K01064]
107508172  WNT9B; protein Wnt-9b [KO:K01064]
107514289  WNT10B; protein Wnt-10b [KO:K01357]
107516694  WNT10A; protein Wnt-10a [KO:K01357]
107519202  WNT11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
107500238  WNT16; protein Wnt-16 [KO:K01558]
107519374  FZD7; frizzled-7 [KO:K02432]
107500880  FZD1; frizzled-1 [KO:K02432]
107508108  FZD2; frizzled-2 [KO:K02235]
107510778  FZD3; frizzled-3 isoform X1 [KO:K02329]
107518567  FZD4; frizzled-4 [KO:K02354]
107505121  FZD8; frizzled-8 [KO:K02375]
107505167  FZD5; frizzled-5 [KO:K02375]
107512212  FZD6; frizzled-6 [KO:K02376]
107511767  FZD9; frizzled-9 [KO:K02842]
107511534  FZD10; frizzled-10 [KO:K02842]
107499654  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
107517194  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107507013  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
107509513  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
107510646  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
107519993  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
107506797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107506285  TCF7L1; transcription factor 7-like 1 [KO:K04490]
107511705  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
107511497  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
107508690  KITLG; LOW QUALITY PROTEIN: kit ligand [KO:K05461]
107499790  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107514939  TYR; tyrosinase [KO:K00505] [EC:]
107519850  TYRP1; LOW QUALITY PROTEIN: 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
107513731  DCT; L-dopachrome tautomerase [KO:K01827] [EC:]
107515476  EDN1; endothelin-1 [KO:K16366]
107513070  EDNRB; endothelin B receptor isoform X1 [KO:K04198]
107516134  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107518173  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107513376  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107506114  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
107519930  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107497081  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:]
107514464  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:]
107509556  CALM2; calmodulin [KO:K02183]
107508927  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
107515457  CALM1; calmodulin [KO:K02183]
107516034  CALM3; calmodulin [KO:K02183]
107501627  calmodulin-like protein 5 [KO:K02183]
107510894  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:]
107512385  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:]
107497167  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:]
107498266  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
107510307  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:]
107516091  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:]
107503061  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:]
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05606  Melanin
Slominski A, Tobin DJ, Shibahara S, Wortsman J.
Melanin pigmentation in mammalian skin and its hormonal regulation.
Physiol Rev 84:1155-228 (2004)
Busca R, Ballotti R.
Cyclic AMP a key messenger in the regulation of skin pigmentation.
Pigment Cell Res 13:60-9 (2000)
Imokawa G.
Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
Pigment Cell Res 17:96-110 (2004)
Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A.
New aspects on the melanocortins and their receptors.
Pharmacol Res 42:393-420 (2000)
Chin L.
The genetics of malignant melanoma: lessons from mouse and man.
Nat Rev Cancer 3:559-70 (2003)
Miller AJ, Mihm MC Jr.
N Engl J Med 355:51-65 (2006)
Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
Pigment Cell Res 16:261-5 (2003)
Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y.
The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
Pigment Cell Res 10:218-28 (1997)
Park HY, Gilchrest BA.
Signaling pathways mediating melanogenesis.
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Park HY, Perez JM, Laursen R, Hara M, Gilchrest BA.
Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain.
J Biol Chem 274:16470-8 (1999)
Sturm RA, Teasdale RD, Box NF.
Human pigmentation genes: identification, structure and consequences of polymorphic variation.
Gene 277:49-62 (2001)
Hearing VJ.
The melanosome: the perfect model for cellular responses to the environment.
Pigment Cell Res 13 Suppl 8:23-34 (2000)
Molina DM, Grewal S, Bardwell L.
Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.
J Biol Chem 280:42051-60 (2005)
ray00350  Tyrosine metabolism
ray04010  MAPK signaling pathway
ray04310  Wnt signaling pathway
ray05218  Melanoma
KO pathway

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