KEGG   PATHWAY: mna04916
mna04916                    Pathway                                

Melanogenesis - Miniopterus natalensis
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.
Organismal Systems; Endocrine system
Pathway map
mna04916  Melanogenesis

Miniopterus natalensis [GN:mna]
107536540  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107524712  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107525737  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107543873  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107530327  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107544136  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
107544933  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107535781  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:]
107531280  EP300; histone acetyltransferase p300 [KO:K04498] [EC:]
107524046  MITF; microphthalmia-associated transcription factor [KO:K09455]
107528239  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107545293  WNT2B; protein Wnt-2b [KO:K00182]
107524863  WNT2; protein Wnt-2 [KO:K00182]
107529919  WNT3A; protein Wnt-3a [KO:K00312]
107530219  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107538446  WNT4; protein Wnt-4 [KO:K00408]
107546464  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
107530635  WNT5A; protein Wnt-5a [KO:K00444]
107524769  WNT6; protein Wnt-6 [KO:K00445]
107537987  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
107534839  WNT7B; protein Wnt-7b [KO:K00572]
107542524  WNT8B; protein Wnt-8b [KO:K00714]
107530103  WNT8A; protein Wnt-8a [KO:K00714]
107529865  WNT9A; protein Wnt-9a [KO:K01064]
107530990  WNT9B; protein Wnt-9b [KO:K01064]
107528238  WNT10B; protein Wnt-10b [KO:K01357]
107524821  WNT10A; protein Wnt-10a [KO:K01357]
107524451  WNT11; protein Wnt-11 [KO:K01384]
107537386  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
107541653  FZD1; frizzled-1 [KO:K02432]
107533927  FZD7; frizzled-7 [KO:K02432]
107528834  FZD2; frizzled-2 [KO:K02235]
107537768  FZD3; frizzled-3 isoform X1 [KO:K02329]
107532452  FZD4; frizzled-4 isoform X1 [KO:K02354]
107525076  FZD8; frizzled-8 [KO:K02375]
107524716  FZD5; frizzled-5 [KO:K02375]
107546030  FZD6; frizzled-6 isoform X1 [KO:K02376]
107526557  FZD9; frizzled-9 [KO:K02842]
107529641  FZD10; frizzled-10 [KO:K02842]
107543463  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107541116  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
107543696  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107544485  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
107527219  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
107524266  CTNNB1; catenin beta-1 [KO:K02105]
107525397  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107528616  TCF7L1; transcription factor 7-like 1 [KO:K04490]
107536455  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
107538292  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
107526843  KITLG; kit ligand isoform X1 [KO:K05461]
107532733  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:]
107542351  HRAS; GTPase HRas isoform X1 [KO:K02833]
107525258  KRAS; GTPase KRas [KO:K07827]
107545303  NRAS; GTPase NRas [KO:K07828]
107534729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
107533801  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
107525695  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107532399  TYR; tyrosinase [KO:K00505] [EC:]
107545566  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
107545906  DCT; L-dopachrome tautomerase [KO:K01827] [EC:]
107530403  EDN1; endothelin-1 [KO:K16366]
107539876  EDNRB; endothelin B receptor [KO:K04198]
107545320  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107540752  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107545079  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107542429  CALML3; calmodulin-like protein 3 [KO:K02183]
107542435  CALML5; calmodulin-like protein 5 [KO:K02183]
107536794  CALM3; calmodulin [KO:K02183]
107540147  CALML6; calmodulin-like protein 6 [KO:K02183]
107544318  CALM2; calmodulin isoform X1 [KO:K02183]
107531584  CALM1; calmodulin [KO:K02183]
107525969  CALML4; calmodulin-like protein 4 [KO:K02183]
107545830  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
107542053  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
107535228  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:]
107527851  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
107544745  PRKCB; protein kinase C beta type [KO:K19662] [EC:]
107540426  PRKCG; protein kinase C gamma type [KO:K19663] [EC:]
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05606  Melanin
Slominski A, Tobin DJ, Shibahara S, Wortsman J.
Melanin pigmentation in mammalian skin and its hormonal regulation.
Physiol Rev 84:1155-228 (2004)
Busca R, Ballotti R.
Cyclic AMP a key messenger in the regulation of skin pigmentation.
Pigment Cell Res 13:60-9 (2000)
Imokawa G.
Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
Pigment Cell Res 17:96-110 (2004)
Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A.
New aspects on the melanocortins and their receptors.
Pharmacol Res 42:393-420 (2000)
Chin L.
The genetics of malignant melanoma: lessons from mouse and man.
Nat Rev Cancer 3:559-70 (2003)
Miller AJ, Mihm MC Jr.
N Engl J Med 355:51-65 (2006)
Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
Pigment Cell Res 16:261-5 (2003)
Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y.
The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
Pigment Cell Res 10:218-28 (1997)
Park HY, Gilchrest BA.
Signaling pathways mediating melanogenesis.
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Park HY, Perez JM, Laursen R, Hara M, Gilchrest BA.
Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain.
J Biol Chem 274:16470-8 (1999)
Sturm RA, Teasdale RD, Box NF.
Human pigmentation genes: identification, structure and consequences of polymorphic variation.
Gene 277:49-62 (2001)
Hearing VJ.
The melanosome: the perfect model for cellular responses to the environment.
Pigment Cell Res 13 Suppl 8:23-34 (2000)
Molina DM, Grewal S, Bardwell L.
Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.
J Biol Chem 280:42051-60 (2005)
mna00350  Tyrosine metabolism
mna04010  MAPK signaling pathway
mna04310  Wnt signaling pathway
mna05218  Melanoma
KO pathway

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