KEGG   PATHWAY: scam04916
Entry
scam04916                   Pathway                                
Name
Melanogenesis - Struthio camelus australis (South African ostrich)
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
scam04916  Melanogenesis
scam04916

Organism
Struthio camelus australis (South African ostrich) [GN:scam]
Gene
104137842  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
104137896  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104138027  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
104138832  FZD10; frizzled-10 [KO:K02842]
104138865  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104139004  FZD3; frizzled-3 isoform X1 [KO:K02329]
104139169  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
104139217  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
104139226  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
104139288  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
104139533  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
104140131  [KO:K04491]
104140969  MITF; microphthalmia-associated transcription factor [KO:K09455]
104141080  WNT8A; protein Wnt-8a [KO:K00714]
104141143  EDNRB; endothelin B receptor [KO:K04198]
104141271  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
104141500  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104141763  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
104141800  WNT8B; protein Wnt-8b [KO:K00714]
104141915  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
104142190  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
104142300  WNT2B; protein Wnt-2b [KO:K00182]
104142365  NRAS; GTPase NRas [KO:K07828]
104142534  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
104142540  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
104142892  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104143004  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104143465  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104143466  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104143715  HRAS; GTPase HRas [KO:K02833]
104143845  KITLG; kit ligand [KO:K05461]
104143885  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
104143916  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
104144009  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
104144024  FZD5; frizzled-5 [KO:K02375]
104144979  CALM2; calmodulin [KO:K02183]
104145759  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
104145778  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
104146139  EDN1; endothelin-1 [KO:K16366]
104146280  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
104146325  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
104146396  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
104146624  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
104146830  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
104147273  WNT5B; protein Wnt-5b [KO:K00444]
104147316  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
104147481  FZD9; frizzled-9 [KO:K02842]
104147642  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
104147765  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
104147952  ASIP; LOW QUALITY PROTEIN: agouti-signaling protein [KO:K08725]
104148880  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
104148956  FZD6; frizzled-6 [KO:K02376]
104150118  WNT9A; protein Wnt-9a [KO:K01064]
104150119  WNT3A; protein Wnt-3a [KO:K00312]
104150184  FZD7; frizzled-7 [KO:K02432]
104150331  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
104150371  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
104150707  [KO:K00408]
104150845  WNT3; proto-oncogene Wnt-3 [KO:K00312]
104150870  WNT9B; protein Wnt-9b [KO:K01064]
104150881  FZD2; frizzled-2 [KO:K02235]
104151125  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
104152131  WNT16; protein Wnt-16 [KO:K01558]
104152361  [KO:K01384]
104152470  CTNNB1; catenin beta-1 [KO:K02105]
104152703  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104152715  WNT7A; protein Wnt-7a [KO:K00572]
104152766  WNT5A; protein Wnt-5a [KO:K00444]
104152790  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
104153274  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
104153503  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
104153578  WNT2; protein Wnt-2 [KO:K00182]
104153641  WNT4; protein Wnt-4 [KO:K00408]
104153661  FZD4; frizzled-4 [KO:K02354]
104153693  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
104153703  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
104153735  WNT10A; protein Wnt-10a [KO:K01357]
104153787  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
104154049  [KO:K04198]
104154112  KRAS; GTPase KRas isoform X1 [KO:K07827]
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
scam00350  Tyrosine metabolism
scam04010  MAPK signaling pathway
scam04310  Wnt signaling pathway
KO pathway
ko04916   

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