KEGG   PATHWAY: opi04916
Entry
opi04916                    Pathway                                
Name
Melanogenesis - Ochotona princeps (American pika)
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
opi04916  Melanogenesis
opi04916

Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101521946  POMC; pro-opiomelanocortin [KO:K05228]
101525188  agouti-signaling protein [KO:K08725]
105941761  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
101526074  neuroendocrine secretory protein 55-like [KO:K04632]
101533323  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101528674  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101529277  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101527552  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101526286  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101528764  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101519430  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101523667  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101517485  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101534210  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101525119  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
101516221  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101532574  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101532689  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101531761  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101533371  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101532921  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101523446  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101517073  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101518802  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101517467  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
101526533  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101519545  WNT2; protein Wnt-2 [KO:K00182]
101535993  WNT2B; protein Wnt-2b [KO:K00182]
101531097  WNT3A; protein Wnt-3a [KO:K00312]
101519718  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101532229  WNT4; protein Wnt-4 [KO:K00408]
101533147  WNT5B; protein Wnt-5b [KO:K00444]
101526139  WNT5A; protein Wnt-5a [KO:K00444]
101518428  WNT6; protein Wnt-6 [KO:K00445]
101525411  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
101527317  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
101535038  WNT8A; protein Wnt-8a [KO:K00714]
101530831  WNT8B; protein Wnt-8b [KO:K00714]
101535462  WNT9A; protein Wnt-9a [KO:K01064]
101519468  WNT9B; protein Wnt-9b [KO:K01064]
101526780  WNT10B; protein Wnt-10b [KO:K01357]
101518185  WNT10A; protein Wnt-10a [KO:K01357]
101530628  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
101521646  WNT16; protein Wnt-16 [KO:K01558]
101528861  FZD1; frizzled-1 [KO:K02432]
101519819  FZD7; frizzled-7 [KO:K02432]
101520542  FZD2; frizzled-2 [KO:K02235]
101528374  FZD3; frizzled-3 [KO:K02329]
101518239  FZD4; frizzled-4 [KO:K02354]
101532093  FZD5; frizzled-5 [KO:K02375]
101517741  FZD8; frizzled-8 [KO:K02375]
101524151  FZD6; frizzled-6 [KO:K02376]
101519524  FZD9; frizzled-9 [KO:K02842]
101520287  FZD10; frizzled-10 [KO:K02842]
101524943  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101517012  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101522688  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101528918  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101516456  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
101533693  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101528934  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
101526730  TCF7; transcription factor 7 isoform X2 [KO:K02620]
101522406  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101521047  TCF7L2; transcription factor 7-like 2 isoform X4 [KO:K04491]
101525298  LEF1; lymphoid enhancer-binding factor 1 isoform X3 [KO:K04492]
101533974  KITLG; kit ligand isoform X1 [KO:K05461]
101536689  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
101531636  HRAS; GTPase HRas [KO:K02833]
101534080  KRAS; GTPase KRas isoform X1 [KO:K07827]
101524465  NRAS; GTPase NRas [KO:K07828]
101534290  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101533612  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105942099  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
101529486  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101520677  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
101516167  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
101518434  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
101526700  EDN1; endothelin-1 [KO:K16366]
101534431  EDNRB; endothelin receptor type B [KO:K04198]
101525340  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101516368  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101531957  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101524349  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101524739  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101529337  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101520538  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101522293  CALM2; calmodulin-2 isoform X1 [KO:K02183]
101516106  CALM1; calmodulin-1 isoform X1 [KO:K02183]
101519171  CALML4; calmodulin-like protein 4 [KO:K02183]
101529054  CALML5; calmodulin-like protein 5 [KO:K02183]
101529298  CALML3; calmodulin-like protein 3 [KO:K02183]
101516467  CALM3; calmodulin-3 [KO:K02183]
101519593  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
101528216  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X11 [KO:K04515] [EC:2.7.11.17]
101524356  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
101535936  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101523549  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101523439  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101534827  PRKCG; protein kinase C gamma type isoform X1 [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
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
opi00350  Tyrosine metabolism
opi04010  MAPK signaling pathway
opi04310  Wnt signaling pathway
opi05218  Melanoma
KO pathway
ko04916   
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