KEGG   PATHWAY: gvr04916
Entry
gvr04916                    Pathway                                
Name
Melanogenesis - Galeopterus variegatus (Sunda flying lemur)
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
gvr04916  Melanogenesis
gvr04916

Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103583204  [KO:K08047] [EC:4.6.1.1]
103583388  [KO:K19663] [EC:2.7.11.13]
103583890  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
103584009  [KO:K09048]
103585039  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103585135  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103585217  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103585560  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
103585949  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
103586074  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
103586228  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103586347  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103586698  FZD5; frizzled-5 [KO:K02375]
103586701  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103587098  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103587175  KITLG; kit ligand isoform X1 [KO:K05461]
103588331  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
103588449  CALM1; calmodulin [KO:K02183]
103588545  [KO:K05858] [EC:3.1.4.11]
103588664  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103588716  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103588804  WNT8B; protein Wnt-8b [KO:K00714]
103588815  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103588854  WNT1; proto-oncogene Wnt-1 [KO:K03209]
103588855  WNT10B; protein Wnt-10b [KO:K01357]
103588863  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103589124  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
103589329  NRAS; GTPase NRas [KO:K07828]
103589553  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
103589593  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103590144  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103590234  WNT5B; protein Wnt-5b [KO:K00444]
103590315  FZD4; frizzled-4 [KO:K02354]
103590322  EDNRB; LOW QUALITY PROTEIN: endothelin B receptor [KO:K04198]
103590450  WNT11; protein Wnt-11 [KO:K01384]
103590618  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103590674  WNT7A; protein Wnt-7a [KO:K00572]
103590972  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
103591300  [KO:K05858] [EC:3.1.4.11]
103591330  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
103591384  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103591440  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
103591872  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103591893  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103592192  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103592399  TCF7; transcription factor 7 isoform X1 [KO:K02620]
103592574  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103592962  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103592983  CALM3; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
103593713  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
103593743  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
103593776  WNT2B; protein Wnt-2b [KO:K00182]
103593898  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
103594556  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
103594788  FZD6; frizzled-6 [KO:K02376]
103594862  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
103594947  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103595017  FZD2; frizzled-2 [KO:K02235]
103595030  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
103595135  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
103595392  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103595701  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
103596055  FZD1; frizzled-1 [KO:K02432]
103596129  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103596484  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
103596654  FZD9; frizzled-9 [KO:K02842]
103596735  FZD10; frizzled-10 [KO:K02842]
103597215  WNT2; protein Wnt-2 [KO:K00182]
103597246  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
103597574  WNT3; proto-oncogene Wnt-3 [KO:K00312]
103597576  WNT9B; protein Wnt-9b [KO:K01064]
103597620  FZD7; LOW QUALITY PROTEIN: frizzled-7 [KO:K02432]
103597918  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103598980  [KO:K00408]
103599501  KRAS; GTPase KRas [KO:K07827]
103599611  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103599669  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103599723  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
103599847  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
103600166  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
103600170  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
103600172  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
103600246  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
103600247  WNT10A; protein Wnt-10a [KO:K01357]
103600324  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103600945  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103601309  [KO:K02183]
103601310  CALML5; calmodulin-like protein 5 [KO:K02183]
103601992  [KO:K02183]
103604077  FZD3; frizzled-3 [KO:K02329]
103605007  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
103605402  WNT8A; protein Wnt-8a [KO:K00714]
103605695  [KO:K00312]
103605697  WNT9A; protein Wnt-9a [KO:K01064]
103606143  ASIP; agouti-signaling protein [KO:K08725]
103606378  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103607489  [KO:K01064]
103608229  EDN1; endothelin-1 [KO:K16366]
103608810  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
103608866  [KO:K04632]
103609951  WNT7B; protein Wnt-7b [KO:K00572]
103610513  HRAS; GTPase HRas isoform X1 [KO:K02833]
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
gvr00350  Tyrosine metabolism
gvr04010  MAPK signaling pathway
gvr04310  Wnt signaling pathway
gvr05218  Melanoma
KO pathway
ko04916   

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