KEGG   PATHWAY: ecb04916
Entry
ecb04916                    Pathway                                
Name
Melanogenesis - Equus caballus (horse)
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
ecb04916  Melanogenesis
ecb04916

Organism
Equus caballus (horse) [GN:ecb]
Gene
100071524  POMC; pro-opiomelanocortin [KO:K05228]
100054335  ASIP; agouti-signaling protein precursor [KO:K08725]
100136907  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
100056464  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100050675  neuroendocrine secretory protein 55 [KO:K04632]
100065563  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100071337  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100055961  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100054305  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100070498  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100051295  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100058891  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100057796  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100066046  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100052828  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100064302  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
100066388  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
100062307  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100064828  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100057002  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100067794  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100063153  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
100055626  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
100069613  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100033918  MITF; microphthalmia-associated transcription factor [KO:K09455]
100058859  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100063931  WNT2B; protein Wnt-2b [KO:K00182]
100056092  WNT2; protein Wnt-2 precursor [KO:K00182]
100049880  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100061145  WNT3A; protein Wnt-3a [KO:K00312]
100071678  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
100056017  WNT5B; protein Wnt-5b [KO:K00444]
100059157  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100058824  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
100053027  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100055450  WNT7A; protein Wnt-7a [KO:K00572]
111768287  protein Wnt-7a [KO:K00572]
100070360  WNT8B; protein Wnt-8b [KO:K00714]
100072609  WNT8A; protein Wnt-8a isoform X3 [KO:K00714]
100061110  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
100063730  WNT9B; protein Wnt-9b [KO:K01064]
100051649  WNT10B; protein Wnt-10b [KO:K01357]
111773843  WNT10A; protein Wnt-10a [KO:K01357]
100064184  WNT11; protein Wnt-11 [KO:K01384]
100071393  WNT16; protein Wnt-16 [KO:K01558]
102147960  FZD7; frizzled-7 [KO:K02432]
106783041  FZD1; frizzled-1 [KO:K02432]
100050809  FZD2; frizzled-2 [KO:K02235]
100054732  FZD3; frizzled-3 [KO:K02329]
100050465  FZD4; frizzled-4 [KO:K02354]
100146215  FZD5; frizzled-5 [KO:K02375]
111771171  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
100056351  FZD6; frizzled-6 [KO:K02376]
100062909  FZD10; frizzled-10 [KO:K02842]
100061635  FZD9; frizzled-9 [KO:K02842]
100051282  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
100063136  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100061612  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100147200  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100147654  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100061033  GSK3B; glycogen synthase kinase-3 beta isoform X6 [KO:K03083] [EC:2.7.11.26]
100055241  CTNNB1; catenin beta-1 [KO:K02105]
100072786  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100067427  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100059146  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100072938  LEF1; lymphoid enhancer-binding factor 1 isoform X6 [KO:K04492]
100034127  KITLG; kit ligand precursor [KO:K05461]
100009704  KIT; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:2.7.10.1]
100055481  HRAS; GTPase HRas isoform X1 [KO:K02833]
100064473  KRAS; GTPase KRas isoform X1 [KO:K07827]
100051785  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
100059469  NRAS; GTPase NRas [KO:K07828]
100051110  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100065996  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100063190  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100057701  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100066173  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100060227  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
100033886  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase precursor [KO:K00506] [EC:1.14.18.-]
100058776  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
100034060  EDN1; endothelin-1 precursor [KO:K16366]
100033875  EDNRB; endothelin receptor type B precursor [KO:K04198]
100055673  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100062085  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100058238  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100057315  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100051558  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100055407  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100051485  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100057133  CALML5; calmodulin-like protein 5 [KO:K02183]
100062752  CALM1; calmodulin-1 [KO:K02183]
100070422  calmodulin-like protein 3 [KO:K02183]
100071150  CALM3; calmodulin-3 [KO:K02183]
100629145  CALM2; calmodulin-2 [KO:K02183]
100064482  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
100052798  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
100064138  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X13 [KO:K04515] [EC:2.7.11.17]
100071654  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100072618  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X6 [KO:K04515] [EC:2.7.11.17]
100146368  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100063318  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100069215  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100062549  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
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
  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
  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
  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
  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
  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
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
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
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
  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
J Biol Chem 274:16470-8 (1999)
DOI:10.1074/jbc.274.23.16470
Reference
  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
  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
  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
ecb00350  Tyrosine metabolism
ecb04010  MAPK signaling pathway
ecb04310  Wnt signaling pathway
ecb05218  Melanoma
KO pathway
ko04916   
LinkDB

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