KEGG   PATHWAY: xla04916
Entry
xla04916                    Pathway                                
Name
Melanogenesis - Xenopus laevis (African 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
xla04916  Melanogenesis
xla04916

Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
380532  pomc.L; pro-opiomelanocortin A precursor [KO:K05228]
373802  pomc.S; pro-opiomelanocortin B precursor [KO:K05228]
108715087  mc1r.S; melanocyte-stimulating hormone receptor [KO:K04199]
399059  gnas.L; uncharacterized protein LOC399059 [KO:K04632]
394414  gnas.S; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
108718988  adcy1.L; adenylate cyclase type 1 isoform X2 [KO:K08041] [EC:4.6.1.1]
108705348  adcy1.S; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
108717252  adcy3.L; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
108718304  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
108707036  adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
108715027  adcy4.L; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
108702898  adcy5.S; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
108701255  adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
108708542  adcy6.L; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
414728  adcy6.S; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
399055  adcy7.L; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
414729  adcy8.S; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
108719413  adcy8.L; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
378610  adcy9.L; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
108703189  adcy9.S; LOW QUALITY PROTEIN: adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
380388  prkacb.S; protein kinase cAMP-activated catalytic subunit beta S homeolog [KO:K04345] [EC:2.7.11.11]
100101276  prkaca.S; protein kinase, cAMP-dependent, alpha catalytic subunit S homeolog [KO:K04345] [EC:2.7.11.11]
108714187  prkacb.L; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108711677  prkaca.L; protein kinase, cAMP-dependent, alpha catalytic subunit L homeolog [KO:K04345] [EC:2.7.11.11]
379764  creb1.S; cAMP responsive element binding protein 1 S homeolog [KO:K05870]
108701473  creb1.L; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100037168  creb3l2.L; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
735076  creb3.S; cAMP responsive element binding protein 3 S homeolog [KO:K09048]
108712546  creb3l2.S; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
108715242  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
108700416  creb3l4.S; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
108699636  creb3l4.L; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
108713769  creb3l1.L; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
495689  crebbp.L; CREB binding protein L homeolog [KO:K04498] [EC:2.3.1.48]
108714480  ep300.L; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108715729  ep300.S; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
373795  crebbp.S; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100337579  mitf.S; melanocyte inducing transcription factor S homeolog [KO:K09455]
373794  mitf.L; melanocyte inducing transcription factor L homeolog [KO:K09455]
373578  wnt1.L; protein Wnt-1 precursor [KO:K03209]
108709815  wnt1.S; protein Wnt-1-like [KO:K03209]
378566  wnt2b.L; protein Wnt-2b-A precursor [KO:K00182]
108713107  protein Wnt-2 [KO:K00182]
108711137  wnt2.L; protein Wnt-2 [KO:K00182]
378679  wnt3a.S; protein Wnt-3a precursor [KO:K00312]
108718689  wnt3a.L; protein Wnt-3 [KO:K00312]
108700866  wnt3.L; proto-oncogene Wnt-3 [KO:K00312]
397706  wnt4.L; protein Wnt-4 isoform 2 precursor [KO:K00408]
108697659  wnt4.S; protein Wnt-4 [KO:K00408]
378689  wnt5a.S; protein Wnt-5a precursor [KO:K00444]
379842  wnt5b.S; protein Wnt-5b precursor [KO:K00444]
108704022  protein Wnt-5a-like isoform X1 [KO:K00444]
108704582  wnt5b.L; protein Wnt-5b-like [KO:K00444]
378676  wnt6.S; protein Wnt-6 [KO:K00445]
108701298  wnt6.L; protein Wnt-6 [KO:K00445]
399364  wnt7b.L; protein Wnt-7b [KO:K00572]
108712529  protein Wnt-7b [KO:K00572]
108700516  wnt7c.S; protein Wnt-7b [KO:K00572]
108705399  protein Wnt-7b [KO:K00572]
108704404  protein Wnt-7a [KO:K00572]
108704038  protein Wnt-7a [KO:K00572]
397970  wnt8a.L; protein Wnt-8 precursor [KO:K00714]
399098  wnt8b.S; protein Wnt-8b precursor [KO:K00714]
108713288  wnt8a.S; protein Wnt-8-like [KO:K00714]
108696239  protein Wnt-8b-like isoform X2 [KO:K00714]
100462925  wnt9b.2.L; protein Wnt-9b isoform X2 [KO:K01064]
100462916  wnt9a.L; protein Wnt-9a isoform X1 [KO:K01064]
108719801  wnt9a.S; protein Wnt-9a isoform X2 [KO:K01064]
108702571  protein Wnt-9b [KO:K01064]
100049784  wnt10a.L; Wnt family member 10A L homeolog [KO:K01357]
108702936  wnt10a.S; protein Wnt-10a [KO:K01357]
108709816  protein Wnt-10b isoform X1 [KO:K01357]
108708545  wnt10b.L; protein Wnt-10b isoform X1 [KO:K01357]
446915  wnt11.S; protein Wnt-11 precursor [KO:K01384]
399441  wnt11b.L; protein Wnt-11b precursor [KO:K01384]
108708822  wnt11.L; protein Wnt-11-like [KO:K01384]
108713100  wnt16.S; protein Wnt-16 [KO:K01558]
108711143  wnt16.L; protein Wnt-16 [KO:K01558]
373817  fzd1.L; frizzled-1 precursor [KO:K02432]
378787  fzd7.L; frizzled class receptor 7 L homeolog [KO:K02432]
108719892  frizzled-1-like [KO:K02432]
108703060  fzd7.S; frizzled-7-B-like [KO:K02432]
399141  fzd2.S; frizzled-2 precursor [KO:K02235]
108700827  frizzled-2-like [KO:K02235]
399190  fzd3.L; frizzled-3 precursor [KO:K02329]
108718300  fzd3.S; frizzled-3-like isoform X2 [KO:K02329]
399192  fzd4.S; frizzled-4 precursor [KO:K02354]
108708760  frizzled-4-like [KO:K02354]
373834  fzd5.S; frizzled-5 precursor [KO:K02375]
373690  fzd8.L; frizzled-8 precursor [KO:K02375]
108701475  fzd5.L; frizzled-5-like [KO:K02375]
399367  fzd8.S; frizzled class receptor 8 S homeolog precursor [KO:K02375]
495007  fzd6.S; frizzled class receptor 6 S homeolog precursor [KO:K02376]
108719371  fzd6.L; frizzled-6 isoform X1 [KO:K02376]
387605  fzd10.S; frizzled class receptor 10 S homeolog precursor [KO:K02842]
387604  fzd10.L; frizzled-10-A precursor [KO:K02842]
108709318  fzd9.S; frizzled-9 [KO:K02842]
108707992  fzd9.L; frizzled-9 [KO:K02842]
397896  gnao1.S; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
108714022  guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
394425  gnaq.L; guanine nucleotide binding protein (G protein), q polypeptide L homeolog [KO:K04634]
399261  gnaq.S; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
444527  dvl3.L; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
399301  dvl2.L; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
108697641  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
108718034  segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100381153  dvl1.L; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
108703580  segment polarity protein dishevelled homolog DVL-2-like isoform X1 [KO:K02353]
399097  gsk3b.L; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
779056  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
399274  ctnnb1.L; catenin beta-1 [KO:K02105]
380441  ctnnb1.S; catenin beta 1 S homeolog [KO:K02105]
398658  tcf7.S; transcription factor 7 S homeolog [KO:K02620]
394281  tcf7l1.S; transcription factor 7-like 1-B [KO:K04490]
397863  tcf7l1.L; transcription factor 7-like 1-A [KO:K04490]
399164  tcf7l2.L; transcription factor 7-like 2 [KO:K04491]
108697306  transcription factor 7-like 2 isoform X1 [KO:K04491]
398238  lef1.L; lymphoid enhancer binding factor 1 L homeolog [KO:K04492]
779101  lef1.S; lymphoid enhancer binding factor 1 S homeolog [KO:K04492]
379817  kitlg.L; KIT ligand L homeolog precursor [KO:K05461]
373760  kitlg.S; KIT ligand S homeolog precursor [KO:K05461]
373772  kit.S; KIT proto-oncogene receptor tyrosine kinase S homeolog precursor [KO:K05091] [EC:2.7.10.1]
373579  kit.L; mast/stem cell growth factor receptor-related protein Kit precursor [KO:K05091] [EC:2.7.10.1]
373727  g67.L; mast/stem cell growth factor receptor-related protein Kit-like [KO:K05091] [EC:2.7.10.1]
399406  hras.L; Harvey rat sarcoma viral oncogene homolog L homeolog [KO:K02833]
397771  kras.L; kirsten rat sarcoma viral oncogene homolog L homeolog [KO:K07827]
100505423  uncharacterized protein LOC100505423 [KO:K07827]
108712520  krasl.S; GTPase KRas isoform X1 [KO:K07827]
108697792  kras.S; GTPase HRas [KO:K07827]
399446  nras.L; GTPase NRas [KO:K07828]
397857  raf1.S; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
108704012  raf1.L; RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
379991  map2k1.L; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108712802  map2k1.S; dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
398985  mapk1.S; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
397785  mapk1.L; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100158309  tyrosinase [KO:K00505] [EC:1.14.18.1]
108719638  tyrosinase [KO:K00505] [EC:1.14.18.1]
108719639  tyrosinase [KO:K00505] [EC:1.14.18.1]
108704650  tyrosinase [KO:K00505] [EC:1.14.18.1]
108708762  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
108710021  tyrosinase [KO:K00505] [EC:1.14.18.1]
121395206  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
380184  tyrp1.L; tyrosinase-related protein 1 L homeolog precursor [KO:K00506] [EC:1.14.18.-]
108706951  tyrp1.S; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
100381161  dct.L; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
100158354  edn1.L; endothelin 1 L homeolog precursor [KO:K16366]
100036806  edn1.S; endothelin 1 S homeolog precursor [KO:K16366]
379394  ednrb2.S; endothelin receptor B subtype 2 S homeolog precursor [KO:K04198]
108698468  ednrb2.L; endothelin-3 receptor-like [KO:K04198]
108708494  ednrb.L; endothelin receptor type B [KO:K04198]
108709766  ednrb.S; endothelin receptor type B [KO:K04198]
379236  gnai3.S; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
380034  gnai1.L; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
399463  gnai1.S; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
779438  gnai2.S; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 S homeolog [KO:K04630]
108714595  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
397692  plcb3.L; phospholipase C beta 3 L homeolog [KO:K05858] [EC:3.1.4.11]
108716399  plcb4.L; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
108716400  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
108699254  plcb2.L; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
445848  plcb4.S; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
733258  plcb1.S; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
380558  calm2.S; calmodulin-2 A [KO:K02183]
606721  calm1.S; calmodulin-1 [KO:K02183]
399259  calm2.L; calmodulin-2 B [KO:K02183]
108711508  calml4.L; calmodulin-like protein 4 isoform X1 [KO:K02183]
108698710  calmodulin-1 [KO:K02183]
108712798  calml4.S; calmodulin-like protein 4 [KO:K02183]
380508  camk2g.S; calcium/calmodulin dependent protein kinase (CaM kinase) II gamma S homeolog [KO:K04515] [EC:2.7.11.17]
397789  camk2b.L; calcium/calmodulin dependent protein kinase (CaM kinase) II beta L homeolog [KO:K04515] [EC:2.7.11.17]
399160  camk2d.S; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
399284  camk2a.S; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
108696257  camk2g.L; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108712641  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
398376  camk2d.L; calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X8 [KO:K04515] [EC:2.7.11.17]
447031  prkca.L; protein kinase C, alpha L homeolog [KO:K02677] [EC:2.7.11.13]
108702159  prkca.S; protein kinase C alpha type isoform X3 [KO:K02677] [EC:2.7.11.13]
108701647  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108703204  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108697820  protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
108696776  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
xla00350  Tyrosine metabolism
xla04010  MAPK signaling pathway
xla04310  Wnt signaling pathway
KO pathway
ko04916   
LinkDB

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