KEGG   PATHWAY: malb04916
Entry
malb04916                   Pathway                                
Name
Melanogenesis - Monopterus albus (swamp eel)
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
malb04916  Melanogenesis
malb04916

Organism
Monopterus albus (swamp eel) [GN:malb]
Gene
109954442  pro-opiomelanocortin-like [KO:K05228]
109955701  pro-opiomelanocortin-like [KO:K05228]
109974767  asip; agouti-signaling protein isoform X1 [KO:K08725]
109962834  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
109970238  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
109970020  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
109961254  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
109957656  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
109958353  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
109971723  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
109952263  LOW QUALITY PROTEIN: adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
109974016  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
109966043  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
109968886  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
109955816  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109971087  LOW QUALITY PROTEIN: adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
109970259  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109972278  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
109972902  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109952408  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109957708  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109958253  cAMP-dependent protein kinase catalytic subunit beta-like isoform X1 [KO:K04345] [EC:2.7.11.11]
109965931  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109972458  cyclic AMP-responsive element-binding protein 1 [KO:K05870]
109968772  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
109964980  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
109956522  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
109960567  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
109953821  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
109970108  creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
109965712  cyclic AMP-responsive element-binding protein 3-like protein 3-A [KO:K09048]
109952643  ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109952679  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
109972268  CREB-binding protein-like [KO:K04498] [EC:2.3.1.48]
109972897  crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
109956104  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
109966771  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
109969901  wnt1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
109964981  protein Wnt-2b-A-like [KO:K00182]
109956425  LOW QUALITY PROTEIN: protein Wnt-2-like [KO:K00182]
109969546  protein Wnt-2b-A [KO:K00182]
109952698  wnt3a; protein Wnt-3a [KO:K00312]
109962806  proto-oncogene Wnt-3 [KO:K00312]
109971989  wnt4; protein Wnt-4 isoform X1 [KO:K00408]
109966188  protein Wnt-4-like [KO:K00408]
109959850  LOW QUALITY PROTEIN: protein Wnt-5b-like [KO:K00444]
109972067  protein Wnt-5a-like [KO:K00444]
109964395  wnt6; protein Wnt-6 [KO:K00445]
109960896  protein Wnt-7b-like isoform X1 [KO:K00572]
109974924  protein Wnt-7b isoform X1 [KO:K00572]
109966055  protein Wnt-7a [KO:K00572]
109970607  protein Wnt-7a-like [KO:K00572]
109961870  wnt8b; protein Wnt-8b [KO:K00714]
109956633  protein Wnt-8-like [KO:K00714]
109956635  protein Wnt-8a-like [KO:K00714]
109952694  wnt9a; protein Wnt-9a [KO:K01064]
109964218  wnt9b; protein Wnt-9b [KO:K01064]
109964405  wnt10a; protein Wnt-10a [KO:K01357]
109969873  wnt10b; protein Wnt-10b isoform X1 [KO:K01357]
109972882  wnt11; protein Wnt-11 [KO:K01384]
109967699  wnt16; protein Wnt-16 [KO:K01558]
109955651  fzd7; frizzled-7 [KO:K02432]
109972978  frizzled-1-like [KO:K02432]
109964237  fzd2; frizzled-2 [KO:K02235]
109954512  LOW QUALITY PROTEIN: frizzled-3-like [KO:K02329]
109969804  fzd3; frizzled-3 [KO:K02329]
109971620  fzd4; frizzled-4 [KO:K02354]
109965176  fzd8; frizzled-8 [KO:K02375]
109967070  frizzled-8-like [KO:K02375]
109972459  frizzled-5-like [KO:K02375]
109966660  fzd6; frizzled-6 [KO:K02376]
109954986  fzd10; frizzled-10 isoform X1 [KO:K02842]
109970544  fzd9; frizzled-9 [KO:K02842]
109962541  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
109964708  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(o) subunit alpha-like [KO:K04534]
109961546  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
109972348  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109969269  segment polarity protein dishevelled homolog DVL-3-like [KO:K02353]
109966475  dvl2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
109966773  dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
109972722  segment polarity protein dishevelled homolog DVL-3-like isoform X1 [KO:K02353]
109965436  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109958342  ctnnb1; catenin beta-1 [KO:K02105]
109963965  catenin beta-1-like [KO:K02105]
109966812  tcf7; transcription factor 7 [KO:K02620]
109954978  transcription factor 7-like 1-A isoform X1 [KO:K04490]
109962891  tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
109955531  lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
109972141  lymphoid enhancer-binding factor 1-like [KO:K04492]
109956329  kitlg; kit ligand [KO:K05461]
109959875  uncharacterized protein LOC109959875 [KO:K05461]
109958402  mast/stem cell growth factor receptor kita-like [KO:K05091] [EC:2.7.10.1]
109962036  mast/stem cell growth factor receptor Kit-like isoform X1 [KO:K05091] [EC:2.7.10.1]
109970774  hras; GTPase HRas [KO:K02833]
109958833  GTPase HRas-like [KO:K07827]
109970760  kras; GTPase KRas isoform X1 [KO:K07827]
109966113  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109971216  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
109974179  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109967020  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
109958888  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
109951143  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109959313  LOW QUALITY PROTEIN: tyrosinase-like [KO:K00505] [EC:1.14.18.1]
109971605  tyr; tyrosinase [KO:K00505] [EC:1.14.18.1]
109958459  5,6-dihydroxyindole-2-carboxylic acid oxidase-like [KO:K00506] [EC:1.14.18.-]
109966528  tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
109958128  dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
109958566  edn1; endothelin-1 [KO:K16366]
109957472  endothelin B receptor-like [KO:K04198]
109974052  endothelin B receptor-like [KO:K04198]
109958995  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109964464  guanine nucleotide-binding protein G(i) subunit alpha-2-like isoform X1 [KO:K04630]
109967176  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
109969698  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109971728  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
109961174  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
109962200  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109962203  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109965817  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
109968365  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
109963360  calml4; calmodulin-like protein 4 [KO:K02183]
109959045  calml6; calmodulin-like protein 6 isoform X1 [KO:K02183]
109974113  calm2; calmodulin [KO:K02183]
109973529  calm3; calmodulin [KO:K02183]
109972810  calmodulin [KO:K02183]
109969805  calmodulin-alpha-like [KO:K02183]
109961060  calcium/calmodulin-dependent protein kinase type II delta chain-like [KO:K04515] [EC:2.7.11.17]
109962949  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109957186  calcium/calmodulin-dependent protein kinase type II delta 1 chain [KO:K04515] [EC:2.7.11.17]
109955133  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
109958384  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
109953086  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109952362  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
109971535  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109971994  protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
109958847  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109968203  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
109970170  protein kinase C alpha type-like 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
malb00350  Tyrosine metabolism
malb04010  MAPK signaling pathway
malb04310  Wnt signaling pathway
KO pathway
ko04916   
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