KEGG   PATHWAY: eee04916
Entry
eee04916                    Pathway                                
Name
Melanogenesis - Electrophorus electricus (electric 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
eee04916  Melanogenesis
eee04916

Organism
Electrophorus electricus (electric eel) [GN:eee]
Gene
113583668  pomc; pro-opiomelanocortin [KO:K05228]
113570090  pro-opiomelanocortin B-like [KO:K05228]
113570869  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
113577854  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
113578881  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
113588648  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
113582988  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
113578463  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
113590334  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
113583134  adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
113591496  adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
113567484  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
113591158  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
113583096  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
113581231  adenylate cyclase type 2-like [KO:K08047] [EC:4.6.1.1]
113584128  adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
113580690  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
113576829  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
113591278  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
113581910  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
113587857  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
113592026  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
113577247  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
113567647  creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
113574777  LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
113576219  cyclic AMP-responsive element-binding protein 3-like protein 3-A [KO:K09048]
113575806  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
113588456  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
113585618  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
113580680  LOW QUALITY PROTEIN: CREB-binding protein-like [KO:K04498] [EC:2.3.1.48]
113588922  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
113576788  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
113574829  ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
113570939  mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
113587086  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
113584444  wnt1; proto-oncogene Wnt-1 [KO:K03209]
113572035  wnt2b; protein Wnt-2b [KO:K00182]
113573613  wnt2; protein Wnt-2 [KO:K00182]
113583078  protein Wnt-2b-A-like [KO:K00182]
113584183  wnt3; proto-oncogene Wnt-3 [KO:K00312]
113587155  wnt3a; protein Wnt-3a [KO:K00312]
113574764  protein Wnt-4-like [KO:K00408]
113586658  wnt4; protein Wnt-4 [KO:K00408]
113578891  protein Wnt-5a-like [KO:K00444]
113584605  protein Wnt-5b isoform X1 [KO:K00444]
113591172  wnt6; protein Wnt-6 [KO:K00445]
113574053  protein Wnt-6-like [KO:K00445]
113583647  protein Wnt-7b [KO:K00572]
113572548  wnt7b; protein Wnt-7b [KO:K00572]
113586314  LOW QUALITY PROTEIN: protein Wnt-7a-like [KO:K00572]
113572305  wnt7a; protein Wnt-7a [KO:K00572]
113580952  protein Wnt-8b [KO:K00714]
113587179  protein Wnt-8c-like [KO:K00714]
113587180  protein Wnt-8a-like [KO:K00714]
113590801  wnt9a; protein Wnt-9a [KO:K01064]
113589912  protein Wnt-9b-like [KO:K01064]
113584450  wnt10b; protein Wnt-10b [KO:K01357]
113591173  wnt10a; protein Wnt-10a [KO:K01357]
113592140  protein Wnt-11-like [KO:K01384]
113590921  protein Wnt-11-like [KO:K01384]
113582698  wnt16; protein Wnt-16 [KO:K01558]
113571960  frizzled-1-like [KO:K02432]
113578539  frizzled-7-A-like [KO:K02432]
113584091  fzd7; frizzled-7 isoform X1 [KO:K02432]
113580237  fzd2; frizzled-2 [KO:K02235]
113578590  frizzled-3-like isoform X1 [KO:K02329]
113581029  frizzled-3-like isoform X1 [KO:K02329]
113588550  fzd4; frizzled-4 [KO:K02354]
113589849  fzd8; frizzled-8 [KO:K02375]
113576052  fzd6; frizzled-6 [KO:K02376]
113577450  fzd9; frizzled-9 [KO:K02842]
113584870  fzd10; frizzled-10 [KO:K02842]
113567826  frizzled-9-like [KO:K02842]
113573596  gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
113579128  guanine nucleotide-binding protein G(o) subunit alpha-like [KO:K04534]
113586947  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
113586948  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
113581283  segment polarity protein dishevelled homolog DVL-1-like [KO:K02353]
113567687  dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
113570143  LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3-like [KO:K02353]
113578914  segment polarity protein dishevelled homolog DVL-1-like [KO:K02353]
113576957  dvl3; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
113578561  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
113580088  LOW QUALITY PROTEIN: catenin beta-1-like [KO:K02105]
113585629  catenin beta-1 isoform X1 [KO:K02105]
113578029  tcf7; transcription factor 7 isoform X1 [KO:K02620]
113589257  transcription factor 7-like 1-A isoform X1 [KO:K04490]
113586207  transcription factor 7-like 1-B [KO:K04490]
113577640  transcription factor 7-like 2 [KO:K04491]
113568617  lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
113583341  kitlg; kit ligand isoform X1 [KO:K05461]
113584395  uncharacterized protein LOC113584395 [KO:K05461]
113591595  mast/stem cell growth factor receptor Kit-like [KO:K05091] [EC:2.7.10.1]
113586384  kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
113579694  GTPase HRas [KO:K02833]
113581312  hras; GTPase HRas [KO:K02833]
113588524  GTPase KRas isoform X1 [KO:K07827]
113589852  GTPase HRas-like [KO:K07827]
113577375  nras; GTPase NRas [KO:K07828]
113580611  RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
113572287  RAF proto-oncogene serine/threonine-protein kinase-like isoform X1 [KO:K04366] [EC:2.7.11.1]
113588584  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113588939  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113584672  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
113585589  mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
113592047  mitogen-activated protein kinase 1-like isoform X1 [KO:K04371] [EC:2.7.11.24]
113578741  tyr; tyrosinase [KO:K00505] [EC:1.14.18.1]
113581657  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
113582223  tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
113590857  dct; LOW QUALITY PROTEIN: L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
113580419  endothelin-1-like [KO:K16366]
113574169  endothelin receptor type B-like isoform X1 [KO:K04198]
113578525  endothelin receptor type B-like [KO:K04198]
113579726  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
113575513  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
113579153  guanine nucleotide-binding protein G(i) subunit alpha-2-like [KO:K04630]
113571585  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
113569349  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
113571340  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
113589181  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like isoform X1 [KO:K05858] [EC:3.1.4.11]
113571600  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
113572657  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like isoform X1 [KO:K05858] [EC:3.1.4.11]
113572658  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like [KO:K05858] [EC:3.1.4.11]
113589466  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
113586011  calmodulin [KO:K02183]
113571726  calmodulin [KO:K02183]
113571128  calmodulin-like isoform X1 [KO:K02183]
113572741  calmodulin [KO:K02183]
113576685  calml4; calmodulin-like protein 4 [KO:K02183]
113572806  calmodulin [KO:K02183]
113571589  calml6; calmodulin-like protein 6 isoform X1 [KO:K02183]
113578627  calmodulin [KO:K02183]
113577666  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
113571482  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
113587336  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
113587439  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
113572944  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
113579297  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
113583472  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
113575317  protein kinase C alpha type-like isoform X1 [KO:K02677] [EC:2.7.11.13]
113590761  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
113588773  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
113580901  protein kinase C beta type isoform X1 [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
eee00350  Tyrosine metabolism
eee04010  MAPK signaling pathway
eee04310  Wnt signaling pathway
KO pathway
ko04916   
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