KEGG   PATHWAY: gacu04916
Entry
gacu04916                   Pathway                                
Name
Melanogenesis - Gymnodraco acuticeps
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
gacu04916  Melanogenesis
gacu04916

Organism
Gymnodraco acuticeps [GN:gacu]
Gene
117533782  pro-opiomelanocortin-like [KO:K05228]
117559272  pomca; proopiomelanocortin a [KO:K05228]
117549124  agouti-signaling protein-like [KO:K08725]
117533318  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
117534189  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
117541950  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
117558416  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
117560499  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
117537493  adcy2a; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
117562961  adcy2b; adenylate cyclase type 2b isoform X1 [KO:K08042] [EC:4.6.1.1]
117538552  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
117554043  adcy3a; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
117539413  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
117549654  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
117541907  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
117542997  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
117549142  adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
117533794  si:dkey-206f10.1; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
117541104  adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
117548476  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
117561607  adcy9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
117548428  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
117555105  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
117558377  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
117561581  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117544461  creb1b; cyclic AMP-responsive element-binding protein 1b [KO:K05870]
117539309  cyclic AMP-responsive element-binding protein 1-like isoform X1 [KO:K05870]
117532700  cyclic AMP-responsive element-binding protein 3-like protein 3-B isoform X1 [KO:K09048]
117546107  creb3l3a; cyclic AMP-responsive element-binding protein 3-like protein 3-A [KO:K09048]
117552450  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
117546942  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
117558670  creb3l3l; cAMP responsive element binding protein 3-like 3 like [KO:K09048]
117560036  LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
117534559  ep300b; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117548406  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
117536236  ep300a; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117561595  crebbpa; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
117543797  mitfa; melanocyte inducing transcription factor a isoform X1 [KO:K09455]
117542989  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
117541847  wnt1; protein Wnt-1 [KO:K03209]
117537802  wnt2; protein Wnt-2 [KO:K00182]
117534176  protein Wnt-2b-A-like [KO:K00182]
117541885  protein Wnt-2b-A isoform X1 [KO:K00182]
117547058  wnt3; proto-oncogene Wnt-3 [KO:K00312]
117558461  wnt3a; protein Wnt-3a [KO:K00312]
117551813  wnt4b; wingless-type MMTV integration site family, member 4b [KO:K00408]
117559501  wnt4; protein Wnt-4a [KO:K00408]
117557912  protein Wnt-5a-like [KO:K00444]
117542864  wnt5b; protein Wnt-5b [KO:K00444]
117553349  wnt6b; protein Wnt-6 [KO:K00445]
117547875  wnt7bb; protein Wnt-7b isoform X1 [KO:K00572]
117543124  protein Wnt-7a [KO:K00572]
117558278  wnt7ba; protein Wnt-7b [KO:K00572]
117538184  wnt8b; protein Wnt-8b isoform X1 [KO:K00714]
117545203  protein Wnt-8a-like [KO:K00714]
117545223  protein Wnt-8a-like isoform X1 [KO:K00714]
117548440  wnt9b; protein Wnt-9b [KO:K01064]
117558341  wnt9a; protein Wnt-9a [KO:K01064]
117553358  wnt10a; protein Wnt-10a isoform X1 [KO:K01357]
117541846  wnt10b; protein Wnt-10b [KO:K01357]
117553025  wnt11; protein Wnt-11 [KO:K01384]
117537178  wnt16; protein Wnt-16 isoform X1 [KO:K01558]
117546857  fzd1; frizzled-1 [KO:K02432]
117560088  frizzled-7-like [KO:K02432]
117548478  fzd2; frizzled-2 [KO:K02235]
117551420  frizzled-3-like [KO:K02329]
117554245  fzd3a; LOW QUALITY PROTEIN: frizzled-3a [KO:K02329]
117552261  fzd4; frizzled-4 [KO:K02354]
117550223  fzd8a; frizzled-8a [KO:K02375]
117544463  fzd5; frizzled-5 [KO:K02375]
117541282  LOW QUALITY PROTEIN: frizzled-8-like [KO:K02375]
117555452  frizzled-6-like [KO:K02376]
117543990  fzd10; LOW QUALITY PROTEIN: frizzled-10 [KO:K02842]
117557400  fzd9b; frizzled-9b [KO:K02842]
117533252  gnao1b; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O, b [KO:K04534]
117542811  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
117543949  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
117537697  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
117532687  LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3-like [KO:K02353]
117552717  dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
117543067  dvl1a; putative segment polarity protein dishevelled homolog DVL1P1 isoform X1 [KO:K02353]
117535811  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117540803  ctnnb1; catenin beta-1 [KO:K02105]
117562919  catenin beta-1-like [KO:K02105]
117540208  tcf7; transcription factor 7 isoform X1 [KO:K02620]
117556347  transcription factor 7-like 1-A [KO:K04490]
117561075  tcf7l1b; transcription factor 7-like 1-B isoform X1 [KO:K04490]
117543165  tcf7l2; LOW QUALITY PROTEIN: transcription factor 7-like 2 [KO:K04491]
117546237  kitlga; kit ligand a [KO:K05461]
117535963  kitlgb; kit ligand b isoform X1 [KO:K05461]
117538061  kitb; KIT proto-oncogene, receptor tyrosine kinase b isoform X1 [KO:K05091] [EC:2.7.10.1]
117555074  kita; mast/stem cell growth factor receptor kita isoform X1 [KO:K05091] [EC:2.7.10.1]
117545900  GTPase HRas [KO:K02833]
117544128  zgc:55558; GTPase HRas [KO:K07827]
117545716  kras; GTPase KRas isoform X1 [KO:K07827]
117542983  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
117538865  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117532733  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
117546153  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
117544100  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117546425  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117534898  tyr; tyrosinase [KO:K00505] [EC:1.14.18.1]
117535274  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
117537979  tyrp1b; tyrosinase-related protein 1b isoform X1 [KO:K00506] [EC:1.14.18.-]
117560911  5,6-dihydroxyindole-2-carboxylic acid oxidase-like [KO:K00506] [EC:1.14.18.-]
117544417  dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
117559277  edn1; endothelin-1 [KO:K16366]
117550745  endothelin receptor type B-like [KO:K04198]
117544411  ednrbb; endothelin receptor type B [KO:K04198]
117556582  ednrba; endothelin receptor Ba isoform X1 [KO:K04198]
117551023  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
117545720  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
117552461  gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
117548100  guanine nucleotide-binding protein G(i) subunit alpha-2-like [KO:K04630]
117541891  gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
117550444  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
117545410  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like isoform X1 [KO:K05858] [EC:3.1.4.11]
117554181  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
117554205  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like isoform X1 [KO:K05858] [EC:3.1.4.11]
117549938  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
117551852  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
117552177  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
117539693  calm1a; calmodulin-1a [KO:K02183]
117554187  calmodulin-1 [KO:K02183]
117549326  calml4a; calmodulin-like protein 4a isoform X1 [KO:K02183]
117544304  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
117551247  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
117547272  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
117543393  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
117560739  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
117548684  si:ch73-374l24.1; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
117561994  prkcaa; protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
117551971  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
117556109  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117543213  prkcg; 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
gacu00350  Tyrosine metabolism
gacu04010  MAPK signaling pathway
gacu04310  Wnt signaling pathway
KO pathway
ko04916   
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