KEGG   PATHWAY: sara04916
Entry
sara04916                   Pathway                                
Name
Melanogenesis - Sorex araneus (European shrew)
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
sara04916  Melanogenesis
sara04916

Organism
Sorex araneus (European shrew) [GN:sara]
Gene
101546548  POMC; pro-opiomelanocortin [KO:K05228]
101550170  ASIP; agouti-signaling protein [KO:K08725]
101557389  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
101539470  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
101557843  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101539413  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101547055  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101539776  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101551819  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101549131  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101543858  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101550559  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101551730  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101539926  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101555578  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101546696  cAMP-dependent protein kinase catalytic subunit-like [KO:K04345] [EC:2.7.11.11]
101554719  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
101552417  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101554214  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101538215  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101543170  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101542980  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101553377  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
101542504  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101558222  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101550863  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
101557092  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101542782  WNT2B; protein Wnt-2b [KO:K00182]
101551266  WNT2; protein Wnt-2 [KO:K00182]
101557532  WNT3A; protein Wnt-3a [KO:K00312]
101538754  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101541062  WNT4; protein Wnt-4 [KO:K00408]
101545125  WNT5B; protein Wnt-5b [KO:K00444]
101544811  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
101552930  WNT6; protein Wnt-6 [KO:K00445]
101551490  WNT7B; protein Wnt-7b [KO:K00572]
101557455  WNT7A; protein Wnt-7a [KO:K00572]
101544351  WNT8A; protein Wnt-8a [KO:K00714]
101537855  WNT8B; protein Wnt-8b [KO:K00714]
101548323  WNT9A; protein Wnt-9a [KO:K01064]
101550368  WNT9B; protein Wnt-9b [KO:K01064]
101557372  WNT10B; protein Wnt-10b [KO:K01357]
101540942  WNT10A; protein Wnt-10a [KO:K01357]
101537834  WNT11; protein Wnt-11 [KO:K01384]
101549154  WNT16; protein Wnt-16 [KO:K01558]
101544647  FZD7; frizzled-7 [KO:K02432]
101547645  FZD1; frizzled-1 [KO:K02432]
101545544  FZD2; frizzled-2 [KO:K02235]
101556188  FZD3; frizzled-3 [KO:K02329]
101539988  FZD4; frizzled-4 [KO:K02354]
101546854  FZD5; frizzled-5 [KO:K02375]
101548121  FZD6; frizzled-6 [KO:K02376]
101544648  FZD9; frizzled-9 [KO:K02842]
101556629  FZD10; frizzled-10 [KO:K02842]
101555708  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
101546592  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X3 [KO:K04534]
101557809  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101549958  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
101544146  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
101541600  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
101536841  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101538379  CTNNB1; catenin beta-1 [KO:K02105]
101540913  TCF7; transcription factor 7 [KO:K02620]
101550691  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101546297  TCF7L2; transcription factor 7-like 2 isoform X2 [KO:K04491]
101547696  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
101540449  KITLG; kit ligand isoform X2 [KO:K05461]
101547411  KIT; mast/stem cell growth factor receptor Kit isoform X2 [KO:K05091] [EC:2.7.10.1]
101546777  HRAS; GTPase HRas [KO:K02833]
101557531  KRAS; GTPase KRas isoform X1 [KO:K07827]
101559343  NRAS; GTPase NRas [KO:K07828]
101545329  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101550720  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101555057  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101559341  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101541587  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
101545848  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101538402  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
101554696  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
101549963  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
101538407  EDN1; endothelin-1 [KO:K16366]
101538515  EDNRB; endothelin B receptor [KO:K04198]
101544375  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101538556  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101545200  guanine nucleotide-binding protein G(i) subunit alpha-like [KO:K04630]
101545636  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101551223  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101546811  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101547690  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101559179  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101554401  CALM1; calmodulin isoform X1 [KO:K02183]
101552535  CALML3; calmodulin-like protein 3 [KO:K02183]
101545302  CALML5; calmodulin-like protein 5 [KO:K02183]
101546941  CALML4; calmodulin-like protein 4 [KO:K02183]
101541555  CALM2; calmodulin [KO:K02183]
101543973  calmodulin-like [KO:K02183]
101559307  CALM3; calmodulin [KO:K02183]
101545625  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101542258  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101549665  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101549827  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
101551961  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101547658  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
101539279  PRKCG; protein kinase C gamma type isoform X1 [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
sara00350  Tyrosine metabolism
sara04010  MAPK signaling pathway
sara04310  Wnt signaling pathway
sara05218  Melanoma
KO pathway
ko04916   
LinkDB

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