KEGG   PATHWAY: tod04916
Entry
tod04916                    Pathway                                
Name
Melanogenesis - Talpa occidentalis (Iberian mole)
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
tod04916  Melanogenesis
tod04916

Organism
Talpa occidentalis (Iberian mole) [GN:tod]
Gene
119258707  POMC; pro-opiomelanocortin [KO:K05228]
119235046  agouti-signaling protein-like isoform X1 [KO:K08725]
119233933  ASIP; agouti-signaling protein isoform X1 [KO:K08725]
119250283  MC1R; LOW QUALITY PROTEIN: melanocyte-stimulating hormone receptor [KO:K04199]
119236970  neuroendocrine secretory protein 55-like [KO:K04632]
119236959  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
119231485  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
119260631  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
119259500  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
119238960  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
119257456  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
119247875  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
119249160  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
119237825  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
119241983  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
119236720  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
119241031  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
119256146  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119232783  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
119235594  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
119246923  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119239846  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119247555  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
119255317  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
119247225  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119241984  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
119230980  MITF; microphthalmia-associated transcription factor isoform X3 [KO:K09455]
119248399  WNT1; proto-oncogene Wnt-1 [KO:K03209]
119236432  WNT2B; protein Wnt-2b [KO:K00182]
119245985  WNT2; protein Wnt-2 [KO:K00182]
119251000  protein Wnt-3a-like [KO:K00312]
119236287  WNT3A; protein Wnt-3a [KO:K00312]
119237039  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
119261460  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
119247849  WNT5B; protein Wnt-5b [KO:K00444]
119256219  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
119247151  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
129146504  WNT7A; protein Wnt-7a [KO:K00572]
119234293  WNT8B; protein Wnt-8b [KO:K00714]
119242726  WNT8A; protein Wnt-8a [KO:K00714]
119232202  WNT9B; protein Wnt-9b [KO:K01064]
119235616  WNT9A; protein Wnt-9a [KO:K01064]
119256220  WNT10A; protein Wnt-10a [KO:K01357]
119248398  WNT10B; protein Wnt-10b [KO:K01357]
119255642  WNT11; protein Wnt-11 [KO:K01384]
119246082  WNT16; protein Wnt-16 [KO:K01558]
119256112  FZD7; frizzled-7 [KO:K02432]
119241918  FZD1; LOW QUALITY PROTEIN: frizzled-1 [KO:K02432]
119231023  FZD2; LOW QUALITY PROTEIN: frizzled-2 [KO:K02235]
119258026  FZD3; frizzled-3 [KO:K02329]
119255697  FZD4; LOW QUALITY PROTEIN: frizzled-4 [KO:K02354]
119244610  FZD8; frizzled-8 [KO:K02375]
119256150  FZD5; frizzled-5 [KO:K02375]
119238879  FZD6; frizzled-6 [KO:K02376]
119245335  FZD10; frizzled-10 [KO:K02842]
119240145  FZD9; frizzled-9 [KO:K02842]
119249230  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
119232758  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
119232660  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
119236345  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
119257340  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
119257489  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119258501  CTNNB1; catenin beta-1 [KO:K02105]
119243471  TCF7; transcription factor 7 isoform X1 [KO:K02620]
119259123  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
119234547  TCF7L2; LOW QUALITY PROTEIN: transcription factor 7-like 2 [KO:K04491]
119242944  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
119247448  KITLG; kit ligand isoform X1 [KO:K05461]
119261155  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
119249824  HRAS; GTPase HRas isoform X1 [KO:K02833]
119247626  KRAS; GTPase KRas isoform X1 [KO:K07827]
119236713  NRAS; GTPase NRas [KO:K07828]
119255730  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119238768  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
119240577  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119234388  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119241775  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119254714  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
119231328  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
119259810  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
119251937  EDN1; endothelin-1 [KO:K16366]
119259900  EDNRB; endothelin receptor type B [KO:K04198]
119235137  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
119260497  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119244853  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
119232648  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
119232657  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X6 [KO:K05858] [EC:3.1.4.11]
119250024  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
119238483  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
119259328  CALM2; calmodulin-2 [KO:K02183]
119244652  calmodulin-like protein 3 [KO:K02183]
119245264  CALML5; calmodulin-like protein 5 [KO:K02183]
119238785  CALML4; calmodulin-like protein 4 [KO:K02183]
119239286  CALM1; calmodulin-1 [KO:K02183]
119256891  calmodulin-1-like [KO:K02183]
119249470  CALM3; calmodulin-3 isoform X1 [KO:K02183]
119234396  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X4 [KO:K04515] [EC:2.7.11.17]
119231251  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119243267  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119243611  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119231758  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119241818  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
119249714  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
tod00350  Tyrosine metabolism
tod04010  MAPK signaling pathway
tod04310  Wnt signaling pathway
tod05218  Melanoma
KO pathway
ko04916   
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