KEGG   PATHWAY: padl04916
Entry
padl04916                   Pathway                                
Name
Melanogenesis - Pygoscelis adeliae (Adelie penguin)
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
padl04916  Melanogenesis
padl04916

Organism
Pygoscelis adeliae (Adelie penguin) [GN:padl]
Gene
103919293  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
103916246  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103915154  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103919638  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103913801  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103916382  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103917604  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103925217  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103923613  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
103926010  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103924510  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103921718  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103915110  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103917529  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
103921793  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
103917006  WNT2; protein Wnt-2 [KO:K00182]
103923556  WNT2B; protein Wnt-2b [KO:K00182]
103924707  WNT3A; protein Wnt-3a [KO:K00312]
103920628  WNT3; proto-oncogene Wnt-3 [KO:K00312]
103921994  protein Wnt-4-like [KO:K00408]
103922005  protein Wnt-4-like [KO:K00408]
103925406  WNT4; protein Wnt-4 [KO:K00408]
103924369  WNT5B; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
103925486  WNT5A; protein Wnt-5a [KO:K00444]
103917663  WNT6; protein Wnt-6 [KO:K00445]
103924109  WNT7A; protein Wnt-7a [KO:K00572]
103916628  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
103915555  WNT8B; LOW QUALITY PROTEIN: protein Wnt-8b [KO:K00714]
103915763  WNT8A; protein Wnt-8a [KO:K00714]
103924706  WNT9A; protein Wnt-9a [KO:K01064]
103920640  WNT9B; protein Wnt-9b [KO:K01064]
103917681  WNT10A; protein Wnt-10a [KO:K01357]
103915171  WNT11; protein Wnt-11 [KO:K01384]
103919182  protein Wnt-11b-like [KO:K01384]
103923858  WNT16; protein Wnt-16 [KO:K01558]
103924411  FZD7; frizzled-7 [KO:K02432]
103922446  FZD1; frizzled-1 [KO:K02432]
103921923  FZD2; frizzled-2 [KO:K02235]
103913242  FZD3; frizzled-3 [KO:K02329]
103916462  FZD4; frizzled-4 [KO:K02354]
103924432  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
103916142  FZD6; LOW QUALITY PROTEIN: frizzled-6 [KO:K02376]
103914342  FZD10; frizzled-10 [KO:K02842]
103916618  FZD9; frizzled-9 [KO:K02842]
103914207  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
103920383  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103922964  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
103917945  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
103922243  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
103914490  CTNNB1; catenin beta-1 [KO:K02105]
103915850  TCF7; transcription factor 7 [KO:K02620]
103918670  TCF7L2; transcription factor 7-like 2 [KO:K04491]
103919538  LEF1; LOW QUALITY PROTEIN: lymphoid enhancer-binding factor 1 [KO:K04492]
103914682  KITLG; kit ligand [KO:K05461]
103926350  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
103916453  HRAS; GTPase HRas [KO:K02833]
103924322  KRAS; GTPase KRas isoform X1 [KO:K07827]
103923578  NRAS; GTPase NRas [KO:K07828]
103915210  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103914812  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103916484  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103922585  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103926027  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
103920349  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
103918279  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
103919091  EDN1; endothelin-1 [KO:K16366]
103923691  EDNRB; endothelin B receptor [KO:K04198]
103925891  endothelin B receptor-like [KO:K04198]
103924080  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
103924081  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
103920595  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
103917177  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-2-like [KO:K04630]
103913124  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103913125  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
103924964  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
103912997  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
103914306  CALM2; calmodulin [KO:K02183]
103914806  CALML4; calmodulin-like protein 4 [KO:K02183]
103922825  calmodulin, striated muscle [KO:K02183]
103915611  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
103915821  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103926125  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
103916720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
103921911  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [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
padl00350  Tyrosine metabolism
padl04010  MAPK signaling pathway
padl04310  Wnt signaling pathway
KO pathway
ko04916   
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