KEGG   PATHWAY: aamp04916
Entry
aamp04916                   Pathway                                
Name
Melanogenesis - Arvicola amphibius (Eurasian water vole)
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
aamp04916  Melanogenesis
aamp04916

Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119808080  Pomc; pro-opiomelanocortin [KO:K05228]
119813977  agouti-signaling protein [KO:K08725]
119814107  Gnas; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
119814944  neuroendocrine secretory protein 55 isoform X1 [KO:K04632]
119800365  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
119809754  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
119807554  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
119800380  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
119824190  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
119822579  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
119801694  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
119823121  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
119811771  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
119800975  Prkacb; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
119802004  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119820446  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119814789  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
119821362  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119801303  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
119826298  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
119806715  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
119822927  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119811558  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
119806804  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
119826419  microphthalmia-associated transcription factor-like [KO:K09455]
119824043  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
119801133  Wnt2b; protein Wnt-2b [KO:K00182]
119807630  Wnt2; protein Wnt-2 [KO:K00182]
119813159  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
119817378  Wnt4; protein Wnt-4 [KO:K00408]
119827774  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
119808280  Wnt5b; protein Wnt-5b [KO:K00444]
119821641  Wnt6; protein Wnt-6 [KO:K00445]
119808152  Wnt7a; protein Wnt-7a [KO:K00572]
119823832  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
119801469  Wnt8b; protein Wnt-8b [KO:K00714]
119815317  Wnt8a; protein Wnt-8a [KO:K00714]
119812884  Wnt9b; protein Wnt-9b [KO:K01064]
119813175  Wnt9a; protein Wnt-9a [KO:K01064]
119821609  Wnt10a; protein Wnt-10a [KO:K01357]
119823873  Wnt10b; protein Wnt-10b [KO:K01357]
119802903  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
119808392  Wnt16; protein Wnt-16 [KO:K01558]
119803883  Fzd7; frizzled-7 [KO:K02432]
119803894  Fzd1; frizzled-1 [KO:K02432]
119813185  Fzd2; frizzled-2 [KO:K02235]
119800348  Fzd3; frizzled-3 [KO:K02329]
119802675  Fzd4; frizzled-4 [KO:K02354]
119802282  Fzd8; frizzled-8 [KO:K02375]
119820296  Fzd5; frizzled-5 [KO:K02375]
119822803  Fzd6; frizzled-6 [KO:K02376]
119825464  Fzd9; frizzled-9 [KO:K02842]
119825673  Fzd10; frizzled-10 [KO:K02842]
119802270  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
119812597  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
119816593  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
119811174  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
119824840  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
119824224  Gsk3b; LOW QUALITY PROTEIN: glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
119808978  Ctnnb1; catenin beta-1 [KO:K02105]
119812304  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
119807723  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
119806595  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
119800683  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
119803565  Kitlg; kit ligand isoform X1 [KO:K05461]
119799770  Kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
119800249  Hras; GTPase HRas isoform X1 [KO:K02833]
119804230  GTPase KRas-like [KO:K07827]
119806318  Kras; GTPase KRas isoform X1 [KO:K07827]
119801497  Nras; GTPase NRas [KO:K07828]
119808272  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119805902  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
119809903  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119827491  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119824680  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119813356  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119803035  Tyr; tyrosinase isoform X1 [KO:K00505] [EC:1.14.18.1]
119817775  Tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
119800423  Dct; L-dopachrome tautomerase isoform X1 [KO:K01827] [EC:5.3.3.12]
119816881  Edn1; endothelin-1 [KO:K16366]
119800039  Ednrb; endothelin receptor type B [KO:K04198]
119800621  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
119809628  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119803872  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
119804038  guanine nucleotide-binding protein G(i) subunit alpha-2-like [KO:K04630]
119814344  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
119814366  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
119814933  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
119824882  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
119821021  Calm3; calmodulin-3 [KO:K02183]
119808332  Calm2; calmodulin-2 [KO:K02183]
119808754  Calml4; calmodulin-like protein 4 [KO:K02183]
119809106  calmodulin-1 [KO:K02183]
119815477  calmodulin-1 [KO:K02183]
119817551  Calml3; calmodulin-like protein 3 [KO:K02183]
119817552  calmodulin-4-like [KO:K02183]
119818370  Calm1; calmodulin-1 [KO:K02183]
119800462  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
119800784  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119808786  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119814221  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119812144  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119822917  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
119820784  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
  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
  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
  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
  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
  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
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
  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
  Authors
Park HY, Gilchrest BA.
  Title
Signaling pathways mediating melanogenesis.
  Journal
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference
  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
  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
  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
  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
aamp00350  Tyrosine metabolism
aamp04010  MAPK signaling pathway
aamp04310  Wnt signaling pathway
aamp05218  Melanoma
KO pathway
ko04916   
LinkDB

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