KEGG   PATHWAY: xtr04916
Entry
xtr04916                    Pathway                                
Name
Melanogenesis - Xenopus tropicalis (tropical clawed frog)
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
xtr04916  Melanogenesis
xtr04916

Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
496777  pomc; pro-opiomelanocortin precursor [KO:K05228]
116408065  asip; agouti-signaling protein [KO:K08725]
100496792  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
407931  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100492373  adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100038110  dnajc27; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100497212  adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100490464  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100493933  adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100127741  adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
549366  uncharacterized protein LOC549366 [KO:K08048] [EC:4.6.1.1]
100126441  adcy9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
549157  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100038053  prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
116407821  putative protein kinase C delta type homolog [KO:K04345] [EC:2.7.11.11]
116407822  putative protein kinase C delta type homolog [KO:K04345] [EC:2.7.11.11]
116407825  protein kinase C delta type-like [KO:K04345] [EC:2.7.11.11]
108648814  protein kinase C delta type [KO:K04345] [EC:2.7.11.11]
100488597  protein kinase C delta type [KO:K04345] [EC:2.7.11.11]
105946713  protein kinase C delta type [KO:K04345] [EC:2.7.11.11]
101731553  serine/threonine-protein kinase N1 [KO:K04345] [EC:2.7.11.11]
116411737  protein kinase C delta type-like [KO:K04345] [EC:2.7.11.11]
407934  creb1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
100127204  creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
780164  creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100145418  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100496679  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101733496  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100101677  crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
734023  ep300; histone acetyltransferase p300 isoform X4 [KO:K04498] [EC:2.3.1.48]
100101790  mitf; microphthalmia-associated transcription factor [KO:K09455]
100491444  wnt1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
100491761  wnt2b; protein Wnt-2b [KO:K00182]
100038261  wnt2; protein Wnt-2 [KO:K00182]
100125198  wnt3; proto-oncogene Wnt-3 [KO:K00312]
100488632  wnt3a; protein Wnt-3a [KO:K00312]
100487954  proto-oncogene Wnt-3 [KO:K00312]
100491282  wnt4; protein Wnt-4 precursor [KO:K00408]
448452  wnt5b; protein Wnt-5b precursor [KO:K00444]
101734372  wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
101733784  wnt6; protein Wnt-6 [KO:K00445]
100145124  wnt7b; protein Wnt-7b [KO:K00572]
100490426  wnt7c; protein Wnt-7b [KO:K00572]
105947033  wnt7a; protein Wnt-7a [KO:K00572]
549962  wnt8a; protein Wnt-8a precursor [KO:K00714]
100496786  wnt8b; protein Wnt-8b isoform X1 [KO:K00714]
100125200  wnt9b; protein Wnt-9b precursor [KO:K01064]
101734951  wnt9a; protein Wnt-9a isoform X1 [KO:K01064]
780228  wnt10b; protein Wnt-10b precursor [KO:K01357]
100485724  wnt10a; protein Wnt-10a [KO:K01357]
493495  wnt11; protein Wnt-11b-1 precursor [KO:K01384]
549489  wnt11b; protein Wnt-11b-2 precursor [KO:K01384]
100158655  wnt11; protein Wnt-11 precursor [KO:K01384]
100125197  wnt16; protein Wnt-16 precursor [KO:K01558]
549495  fzd7; frizzled-7 precursor [KO:K02432]
100145232  fzd1; frizzled-1 precursor [KO:K02432]
493345  fzd2; frizzled-2 precursor [KO:K02235]
100038082  fzd3; frizzled-3 precursor [KO:K02329]
100497693  fzd4; frizzled-4 [KO:K02354]
100038274  fzd8; frizzled-8 precursor [KO:K02375]
100488110  fzd5; frizzled-5 [KO:K02375]
100490861  fzd6; frizzled-6 precursor [KO:K02376]
448162  fzd10; frizzled-10 precursor [KO:K02842]
100487936  fzd9; frizzled-9 [KO:K02842]
549749  gnao1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
733773  gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100144702  dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100144639  dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
780117  dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
100489648  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
549712  ctnnb1; catenin beta-1 [KO:K02105]
395061  tcf7; transcription factor 7 [KO:K02620]
448107  tcf7l1; transcription factor 7-like 1 [KO:K04490]
100101719  tcf7l2; transcription factor 7-like 2 [KO:K04491]
100493178  lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
733847  kitlg; kit ligand precursor [KO:K05461]
100216090  kit; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:2.7.10.1]
549757  hras; GTPase HRas [KO:K02833]
493396  kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
100485959  krasl; GTPase KRas isoform X2 [KO:K07827]
549517  nras; GTPase NRas [KO:K07828]
549871  raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
493420  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
549881  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100125152  tyr; tyrosinase precursor [KO:K00505] [EC:1.14.18.1]
100486242  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
100492641  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
549230  tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase precursor [KO:K00506] [EC:1.14.18.-]
549915  dct; L-dopachrome tautomerase precursor [KO:K01827] [EC:5.3.3.12]
100144700  edn1; endothelin-1 [KO:K16366]
779931  ednrb; endothelin B receptor precursor [KO:K04198]
780133  ednrb2; endothelin receptor B subtype 2 precursor [KO:K04198]
394861  gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
496962  gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100038283  gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
780394  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100125098  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100487267  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101734935  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
493522  calm1; calmodulin [KO:K02183]
100496298  calm2; calmodulin-2 [KO:K02183]
496530  calml4; calmodulin-like protein 4 [KO:K02183]
780379  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
100135023  camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
100101771  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100135711  camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
780209  prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100038043  prkcb; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100496779  prkcg; protein kinase C gamma type isoform X2 [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
xtr00350  Tyrosine metabolism
xtr04010  MAPK signaling pathway
xtr04310  Wnt signaling pathway
KO pathway
ko04916   
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