KEGG   PATHWAY: cabi04916
Entry
cabi04916                   Pathway                                
Name
Melanogenesis - Chelonoidis abingdonii (Abingdon island giant tortoise)
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
cabi04916  Melanogenesis
cabi04916

Organism
Chelonoidis abingdonii (Abingdon island giant tortoise) [GN:cabi]
Gene
116815009  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
116815119  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
116815223  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
116815230  WNT6; LOW QUALITY PROTEIN: protein Wnt-6 [KO:K00445]
116815232  WNT10A; protein Wnt-10a [KO:K01357]
116815736  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
116816076  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
116816093  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
116816303  [KO:K01064]
116816304  [KO:K00312]
116816669  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
116816696  [KO:K04632]
116816893  CALM1; calmodulin-1 [KO:K02183]
116816930  NRAS; GTPase NRas [KO:K07828]
116817600  WNT4; protein Wnt-4 [KO:K00408]
116817901  [KO:K04345] [EC:2.7.11.11]
116818056  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
116818084  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
116818183  CALM2; calmodulin-2 [KO:K02183]
116818245  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116819019  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116819953  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
116820109  FZD6; frizzled-6 [KO:K02376]
116820235  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116820405  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
116820735  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
116820748  HRAS; GTPase HRas [KO:K02833]
116821226  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
116821242  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
116821709  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
116822411  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
116822806  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116823168  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
116823422  WNT8A; protein Wnt-8a [KO:K00714]
116823610  WNT8B; protein Wnt-8b [KO:K00714]
116823615  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116824611  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
116824639  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
116825142  ASIP; agouti-signaling protein [KO:K08725]
116825358  [KO:K04515] [EC:2.7.11.17]
116825420  [KO:K04345] [EC:2.7.11.11]
116825530  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116825535  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
116826053  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
116826454  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
116826639  TCF7; transcription factor 7 isoform X1 [KO:K02620]
116826976  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116827701  WNT1; proto-oncogene Wnt-1 [KO:K03209]
116827788  WNT10B; protein Wnt-10b [KO:K01357]
116827794  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
116827902  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
116827992  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
116828360  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
116828944  FZD9; frizzled-9 [KO:K02842]
116829048  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116829549  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
116829550  FZD4; frizzled-4 [KO:K02354]
116830341  KRAS; GTPase KRas isoform X1 [KO:K07827]
116830805  [KO:K04634]
116830867  POMC; pro-opiomelanocortin [KO:K05228]
116830876  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
116831111  FZD3; frizzled-3 isoform X1 [KO:K02329]
116831316  FZD10; frizzled-10 [KO:K02842]
116832380  [KO:K19663] [EC:2.7.11.13]
116832519  EDN1; endothelin-1 [KO:K16366]
116832677  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
116832743  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
116833087  WNT5A; protein Wnt-5a [KO:K00444]
116833219  [KO:K04198]
116834011  [KO:K05858] [EC:3.1.4.11]
116834128  FZD2; frizzled-2 [KO:K02235]
116834246  WNT16; protein Wnt-16 [KO:K01558]
116834547  WNT5B; protein Wnt-5b [KO:K00444]
116834610  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
116834703  [KO:K01384]
116834742  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
116835238  CALM3; calmodulin-3 [KO:K02183]
116835344  FZD1; frizzled-1 [KO:K02432]
116835748  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116836010  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
116836072  FZD7; frizzled-7 [KO:K02432]
116836173  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
116836359  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116836472  EDNRB; endothelin receptor type B [KO:K04198]
116836497  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116836951  [KO:K09048]
116837064  KITLG; kit ligand [KO:K05461]
116837447  [KO:K00408]
116837565  [KO:K04630]
116837678  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
116837780  WNT2B; protein Wnt-2b [KO:K00182]
116837811  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116838571  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
116838611  WNT2; protein Wnt-2 [KO:K00182]
116838816  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
116838844  [KO:K02183]
116839023  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
116839194  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
116840002  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
116840024  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
116840087  [KO:K07827]
116840147  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
116840158  WNT9B; protein Wnt-9b [KO:K01064]
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
cabi00350  Tyrosine metabolism
cabi04010  MAPK signaling pathway
cabi04310  Wnt signaling pathway
KO pathway
ko04916   

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