KEGG   PATHWAY: npo04916
Entry
npo04916                    Pathway                                
Name
Melanogenesis - Nyctereutes procyonoides (raccoon dog)
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
npo04916  Melanogenesis
npo04916

Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129511116  POMC; pro-opiomelanocortin [KO:K05228]
129496802  ASIP; agouti-signaling protein [KO:K08725]
129497916  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
129497792  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
129497848  neuroendocrine secretory protein 55 [KO:K04632]
129512833  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632]
129515724  LOW QUALITY PROTEIN: adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
129516202  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
129498939  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
129510932  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
129499511  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
129503910  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
129517234  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
129513386  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
129502672  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
129519450  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129519960  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129521768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
129522997  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129518269  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
129508719  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
129494799  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129503105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129515926  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129522278  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129511409  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
129520280  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
129521570  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
129517408  WNT1; proto-oncogene Wnt-1 [KO:K03209]
129501220  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
129502893  WNT2; protein Wnt-2 [KO:K00182]
129506798  WNT3; LOW QUALITY PROTEIN: proto-oncogene Wnt-3 [KO:K00312]
129515047  WNT3A; protein Wnt-3a [KO:K00312]
129513678  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
129503341  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
129521805  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
129523023  WNT6; protein Wnt-6 [KO:K00445]
129511925  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
129521980  WNT7A; protein Wnt-7a [KO:K00572]
129494611  WNT8A; protein Wnt-8a [KO:K00714]
129493561  WNT8B; protein Wnt-8b [KO:K00714]
129500703  WNT9B; protein Wnt-9b [KO:K01064]
129514999  WNT9A; protein Wnt-9a [KO:K01064]
129522994  WNT10A; protein Wnt-10a [KO:K01357]
129517200  WNT10B; protein Wnt-10b [KO:K01357]
129506696  WNT11; protein Wnt-11 [KO:K01384]
129502963  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
129498263  FZD1; frizzled-1 [KO:K02432]
129522877  FZD7; frizzled-7 isoform X1 [KO:K02432]
129510346  FZD2; frizzled-2 [KO:K02235]
129493707  FZD3; frizzled-3 [KO:K02329]
129506743  FZD4; frizzled-4 [KO:K02354]
129499073  FZD8; frizzled-8 [KO:K02375]
129522741  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
129495713  FZD6; frizzled-6 isoform X1 [KO:K02376]
129508175  FZD10; frizzled-10 [KO:K02842]
129519529  FZD9; frizzled-9 [KO:K02842]
129513852  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
129500644  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129496981  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
129497764  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
129498669  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
129503652  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129506984  CTNNB1; catenin beta-1 [KO:K02105]
129494859  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129510910  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129493862  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129521205  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129516966  KITLG; kit ligand isoform X1 [KO:K05461]
129505409  mast/stem cell growth factor receptor Kit-like isoform X1 [KO:K05091] [EC:2.7.10.1]
129517366  mast/stem cell growth factor receptor Kit-like [KO:K05091] [EC:2.7.10.1]
129520654  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
129494224  HRAS; GTPase HRas isoform X1 [KO:K02833]
129505561  KRAS; GTPase KRas isoform X1 [KO:K07827]
129501466  NRAS; GTPase NRas [KO:K07828]
129522592  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129506345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129522322  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129506715  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
129495245  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
129516505  DCT; L-dopachrome tautomerase isoform X1 [KO:K01827] [EC:5.3.3.12]
129508391  EDN1; endothelin-1 [KO:K16366]
129516513  EDNRB; endothelin receptor type B [KO:K04198]
129494269  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129519569  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
129522106  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
129496894  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
129504276  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
129497646  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129500550  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129495972  CALM1; calmodulin-1 [KO:K02183]
129497741  CALML6; calmodulin-like protein 6 [KO:K02183]
129506414  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
129500769  CALM3; calmodulin-3 [KO:K02183]
129511712  CALM2; calmodulin-2 isoform X1 [KO:K02183]
129513685  calmodulin-like protein 3 [KO:K02183]
129513765  CALML5; calmodulin-like protein 5 [KO:K02183]
129515997  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129509461  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129509507  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129521159  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129494612  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
129519978  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
129500385  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
npo00350  Tyrosine metabolism
npo04010  MAPK signaling pathway
npo04310  Wnt signaling pathway
npo05218  Melanoma
KO pathway
ko04916   
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