KEGG   PATHWAY: aml04916
Entry
aml04916                    Pathway                                
Name
Melanogenesis - Ailuropoda melanoleuca (giant panda)
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 system
Pathway map
aml04916  Melanogenesis
aml04916

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100464171  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
100464196  NRAS; GTPase NRas [KO:K07828]
100464621  FZD6; frizzled-6 isoform X1 [KO:K02376]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465243  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
100465448  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100465526  EDNRB; endothelin receptor type B [KO:K04198]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100465982  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100466067  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100466130  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
100466256  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X5 [KO:K04515] [EC:2.7.11.17]
100466408  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100466672  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467156  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
100467643  [KO:K01357]
100467719  TCF7L2; transcription factor 7-like 2 isoform X6 [KO:K04491]
100467779  FZD8; frizzled-8 [KO:K02375]
100467896  WNT6; protein Wnt-6 [KO:K00445]
100468152  ASIP; agouti-signaling protein isoform X1 [KO:K08725]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468561  WNT11; protein Wnt-11 [KO:K01384]
100468584  WNT4; protein Wnt-4 [KO:K00408]
100468694  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100468831  FZD3; frizzled-3 isoform X1 [KO:K02329]
100469196  FZD1; frizzled-1 [KO:K02432]
100469231  [KO:K04632]
100469249  FZD2; frizzled-2 [KO:K02235]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469765  FZD9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
100469856  KITLG; kit ligand isoform X1 [KO:K05461]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100470200  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
100470379  FZD4; frizzled-4 [KO:K02354]
100470867  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100470909  CALM2; calmodulin-2 [KO:K02183]
100470926  EDN1; endothelin-1 [KO:K16366]
100471143  MITF; microphthalmia-associated transcription factor isoform X3 [KO:K09455]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471555  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100471767  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100471972  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
100472104  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100472122  CALM3; calmodulin-3 [KO:K02183]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100472460  WNT9B; protein Wnt-9b [KO:K01064]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473680  [KO:K04632]
100473835  WNT3A; protein Wnt-3a [KO:K00312]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100473854  WNT5B; protein Wnt-5b isoform X3 [KO:K00444]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474459  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X3 [KO:K04515] [EC:2.7.11.17]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100474982  WNT7B; protein Wnt-7b [KO:K00572]
100475007  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100475022  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
100475103  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
100475153  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
100475265  WNT10B; protein Wnt-10b isoform X1 [KO:K01357]
100475467  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515] [EC:2.7.11.17]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476528  TCF7; transcription factor 7 isoform X2 [KO:K02620]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100477711  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100477834  CTNNB1; catenin beta-1 [KO:K02105]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100478243  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
100478600  CALML6; calmodulin-like protein 6 [KO:K02183]
100478649  FZD5; frizzled-5 [KO:K02375]
100478732  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100479224  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100479765  FZD10; frizzled-10 [KO:K02842]
100480005  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100480008  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100480237  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480690  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100481177  CALM1; calmodulin-1 [KO:K02183]
100481656  POMC; LOW QUALITY PROTEIN: pro-opiomelanocortin [KO:K05228]
100481665  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
100481684  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100483482  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100484068  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100484519  [KO:K02183]
100484531  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100484770  [KO:K02183]
100484933  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109489608  FZD7; frizzled-7 [KO:K02432]
117795031  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
117799706  [KO:K02183]
Compound
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05606  Melanin
Reference
PMID:15383650
  Authors
Slominski A, Tobin DJ, Shibahara S, Wortsman J.
  Title
Melanin pigmentation in mammalian skin and its hormonal regulation.
  Journal
Physiol Rev 84:1155-228 (2004)
DOI:10.1152/physrev.00044.2003
Reference
PMID:10841026
  Authors
Busca R, Ballotti R.
  Title
Cyclic AMP a key messenger in the regulation of skin pigmentation.
  Journal
Pigment Cell Res 13:60-9 (2000)
DOI:10.1034/j.1600-0749.2000.130203.x
Reference
PMID:15016298
  Authors
Imokawa G.
  Title
Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
  Journal
Pigment Cell Res 17:96-110 (2004)
DOI:10.1111/j.1600-0749.2003.00126.x
Reference
PMID:11023702
  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
Pharmacol Res 42:393-420 (2000)
DOI:10.1006/phrs.2000.0725
Reference
PMID:12894244
  Authors
Chin L.
  Title
The genetics of malignant melanoma: lessons from mouse and man.
  Journal
Nat Rev Cancer 3:559-70 (2003)
DOI:10.1038/nrc1145
Reference
PMID:16822996
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
PMID:12753399
  Authors
Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
  Title
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
  Journal
Pigment Cell Res 16:261-5 (2003)
DOI:10.1034/j.1600-0749.2003.00039.x
Reference
PMID:9263329
  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
Pigment Cell Res 10:218-28 (1997)
DOI:10.1111/j.1600-0749.1997.tb00488.x
Reference
PMID:10643996
  Authors
Park HY, Gilchrest BA.
  Title
Signaling pathways mediating melanogenesis.
  Journal
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference
PMID:10347209
  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
J Biol Chem 274:16470-8 (1999)
DOI:10.1074/jbc.274.23.16470
Reference
PMID:11602344
  Authors
Sturm RA, Teasdale RD, Box NF.
  Title
Human pigmentation genes: identification, structure and consequences of polymorphic variation.
  Journal
Gene 277:49-62 (2001)
DOI:10.1016/S0378-1119(01)00694-1
Reference
PMID:11041354
  Authors
Hearing VJ.
  Title
The melanosome: the perfect model for cellular responses to the environment.
  Journal
Pigment Cell Res 13 Suppl 8:23-34 (2000)
DOI:10.1034/j.1600-0749.13.s8.7.x
Reference
PMID:16246839
  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
J Biol Chem 280:42051-60 (2005)
DOI:10.1074/jbc.M510590200
Related
pathway
aml00350  Tyrosine metabolism
aml04010  MAPK signaling pathway
aml04310  Wnt signaling pathway
aml05218  Melanoma
KO pathway
ko04916   

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