KEGG   PATHWAY: emc04916
Entry
emc04916                    Pathway                                
Name
Melanogenesis - Eublepharis macularius (Leopard gecko)
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
emc04916  Melanogenesis
emc04916

Organism
Eublepharis macularius (Leopard gecko) [GN:emc]
Gene
129331209  POMC; pro-opiomelanocortin [KO:K05228]
129330912  ASIP; agouti-signaling protein [KO:K08725]
129329987  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
129337825  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
129333200  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
129335670  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
129340558  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
129325033  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
129327435  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
129344146  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
129333839  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
129338722  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129329909  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129327293  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
129323822  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129334192  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
129335674  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
129330760  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129336626  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
129325133  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129340604  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
129335504  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
129328124  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
129328332  WNT1; proto-oncogene Wnt-1 [KO:K03209]
129330120  WNT2B; protein Wnt-2b [KO:K00182]
129337583  WNT3A; protein Wnt-3a [KO:K00312]
129338642  WNT3; proto-oncogene Wnt-3 [KO:K00312]
129344807  WNT4; protein Wnt-4 [KO:K00408]
129328177  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
129335858  WNT5B; protein Wnt-5b [KO:K00444]
129324530  WNT6; protein Wnt-6 [KO:K00445]
129328066  WNT7A; protein Wnt-7a [KO:K00572]
129344208  WNT7B; protein Wnt-7b [KO:K00572]
129328806  WNT8A; protein Wnt-8a [KO:K00714]
129332734  WNT8B; protein Wnt-8b [KO:K00714]
129337267  WNT9A; LOW QUALITY PROTEIN: protein Wnt-9a [KO:K01064]
129339092  WNT9B; protein Wnt-9b [KO:K01064]
129328813  WNT10B; protein Wnt-10b [KO:K01357]
129324165  WNT10A; protein Wnt-10a [KO:K01357]
129325946  WNT11; protein Wnt-11 [KO:K01384]
129336006  WNT16; protein Wnt-16 [KO:K01558]
129324412  FZD7; frizzled-7 [KO:K02432]
129337842  FZD1; frizzled-1 [KO:K02432]
129340460  FZD2; frizzled-2 [KO:K02235]
129330041  FZD3; frizzled-3 isoform X1 [KO:K02329]
129325778  FZD4; frizzled-4 [KO:K02354]
129323720  FZD5; frizzled-5 [KO:K02375]
129337994  FZD8; frizzled-8 [KO:K02375]
129333380  FZD6; frizzled-6 [KO:K02376]
129345109  FZD9; frizzled-9 [KO:K02842]
129341005  FZD10; frizzled-10 [KO:K02842]
129343925  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
129334311  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129340364  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
129331902  DVL3; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
129344478  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
129345278  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129337938  CTNNB1; catenin beta-1 [KO:K02105]
129328416  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129342060  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129331736  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129337067  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129335587  KITLG; kit ligand isoform X1 [KO:K05461]
129336533  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
129324311  HRAS; GTPase HRas [KO:K02833]
129336091  KRAS; GTPase KRas isoform X1 [KO:K07827]
129338629  GTPase HRas-like [KO:K07827]
129330049  NRAS; GTPase NRas [KO:K07828]
129328096  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129345582  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129330130  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129341079  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129338355  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129326090  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
129334721  TYRP1; LOW QUALITY PROTEIN: 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
129326060  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
129333548  EDN1; endothelin-1 [KO:K16366]
129340918  endothelin receptor type B-like [KO:K04198]
129325688  EDNRB; endothelin receptor type B [KO:K04198]
129329743  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
129335516  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129327409  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
129324816  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
129326725  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
129338761  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129327269  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
129345633  CALML4; calmodulin-like protein 4 [KO:K02183]
129334948  calmodulin-A-like [KO:K02183]
129335564  uncharacterized protein LOC129335564 [KO:K02183]
129335565  calmodulin, flagellar-like [KO:K02183]
129324040  CALM1; calmodulin-1 [KO:K02183]
129342822  CALM3; calmodulin-3 isoform X1 [KO:K02183]
129332838  CALM2; calmodulin-2 [KO:K02183]
129338701  calmodulin-1 [KO:K02183]
129344686  CALML6; calmodulin-like protein 6 [KO:K02183]
129341994  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129336885  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129332076  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129326894  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
129328100  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
129340241  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
129338720  PRKCG; protein kinase C gamma type [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
emc00350  Tyrosine metabolism
emc04010  MAPK signaling pathway
emc04310  Wnt signaling pathway
KO pathway
ko04916   
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