KEGG   PATHWAY: hai04916
Entry
hai04916                    Pathway                                
Name
Melanogenesis - Hipposideros armiger (great roundleaf bat)
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
hai04916  Melanogenesis
hai04916

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109392186  POMC; pro-opiomelanocortin [KO:K05228]
109389586  ASIP; agouti-signaling protein [KO:K08725]
109380071  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
109380072  neuroendocrine secretory protein 55 [KO:K04632]
109373011  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109375976  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109385186  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
109393593  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
109387200  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109393238  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
109383261  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109372359  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
109392133  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109385440  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109394225  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109388316  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
109373471  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
109393756  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
109388532  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
109390233  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
109388636  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
109392135  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109392262  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
109387441  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
109393219  WNT1; proto-oncogene Wnt-1 [KO:K03209]
109391554  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
109389334  WNT2; protein Wnt-2 [KO:K00182]
109380253  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
109377253  WNT3A; protein Wnt-3a [KO:K00312]
109396735  WNT4; protein Wnt-4 [KO:K00408]
109388973  WNT5B; protein Wnt-5b [KO:K00444]
109389090  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
109380535  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
109387605  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
109390460  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
109379609  WNT8B; protein Wnt-8b [KO:K00714]
109392505  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
109380276  WNT9B; protein Wnt-9b [KO:K01064]
109392784  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
109380555  WNT10A; protein Wnt-10a [KO:K01357]
109393213  WNT10B; protein Wnt-10b [KO:K01357]
109386296  WNT11; protein Wnt-11 [KO:K01384]
109371280  WNT16; protein Wnt-16 [KO:K01558]
109379180  FZD7; frizzled-7 [KO:K02432]
109395312  FZD1; frizzled-1 [KO:K02432]
109394953  FZD2; frizzled-2 [KO:K02235]
109379491  FZD3; frizzled-3 isoform X1 [KO:K02329]
109383276  FZD4; frizzled-4 [KO:K02354]
109388314  FZD5; frizzled-5 [KO:K02375]
109376300  FZD6; frizzled-6 [KO:K02376]
109384984  FZD9; frizzled-9 [KO:K02842]
109396791  FZD10; frizzled-10 [KO:K02842]
109385746  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109371312  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
109391189  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
109394615  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
109388396  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109377341  CTNNB1; catenin beta-1 [KO:K02105]
109382635  TCF7; transcription factor 7 isoform X1 [KO:K02620]
109371340  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
109384898  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
109379461  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
109376220  KITLG; kit ligand [KO:K05461]
109381816  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
109375639  HRAS; GTPase HRas isoform X1 [KO:K02833]
109385150  GTPase HRas-like [KO:K02833]
109389264  KRAS; GTPase KRas isoform X1 [KO:K07827]
109377015  NRAS; GTPase NRas [KO:K07828]
109384548  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109374039  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
109373396  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
109395407  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
109375416  EDN1; endothelin-1 [KO:K16366]
109389071  EDNRB; endothelin B receptor [KO:K04198]
109377665  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109375288  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
109392892  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109378976  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
109378977  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109384329  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109383976  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109382670  CALM1; calmodulin [KO:K02183]
109380340  calmodulin-like [KO:K02183]
109391149  CALML6; calmodulin-like protein 6 [KO:K02183]
109383794  calmodulin-like protein 3 [KO:K02183]
109383796  calmodulin-like [KO:K02183]
109372230  CALM3; calmodulin [KO:K02183]
109389917  CALM2; calmodulin [KO:K02183]
109372542  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109373019  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109375001  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
109390284  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109380289  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109372505  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
hai00350  Tyrosine metabolism
hai04010  MAPK signaling pathway
hai04310  Wnt signaling pathway
hai05218  Melanoma
KO pathway
ko04916   
LinkDB

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