KEGG   PATHWAY: mze04916
Entry
mze04916                    Pathway                                
Name
Melanogenesis - Maylandia zebra (zebra mbuna)
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
mze04916  Melanogenesis
mze04916

Organism
Maylandia zebra (zebra mbuna) [GN:mze]
Gene
101487793  pomc; pro-opiomelanocortin [KO:K05228]
101481156  pro-opiomelanocortin-like [KO:K05228]
101475601  pro-opiomelanocortin [KO:K05228]
101481141  agouti-signaling protein [KO:K08725]
101470947  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
101481065  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
101467861  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
101466326  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101470179  adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101464825  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101474342  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101472004  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101468640  adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101480556  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101473262  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101483853  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101480238  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101468839  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101465620  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101473876  adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
101477119  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101466373  adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
101482847  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101482575  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101470440  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101473852  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101465790  cyclic AMP-responsive element-binding protein 1 [KO:K05870]
101472017  creb1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
101466226  creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
101469085  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
101480575  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101487513  cyclic AMP-responsive element-binding protein 3-like protein 3-B [KO:K09048]
101486384  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101483965  cyclic AMP-responsive element-binding protein 3-like protein 3-B isoform X2 [KO:K09048]
101467023  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101478121  ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101468013  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101476833  crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101473186  mitfa; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
101473787  mitfb; microphthalmia-associated transcription factor [KO:K09455]
101475965  wnt1; proto-oncogene Wnt-1 [KO:K03209]
101464295  protein Wnt-2b-A [KO:K00182]
101476551  protein Wnt-2b-A [KO:K00182]
101464519  wnt2; protein Wnt-2 [KO:K00182]
101472392  wnt3a; protein Wnt-3a [KO:K00312]
101469754  proto-oncogene Wnt-3 isoform X1 [KO:K00312]
101479331  protein Wnt-4 [KO:K00408]
101473265  wnt4; protein Wnt-4 [KO:K00408]
101487154  protein Wnt-5b isoform X1 [KO:K00444]
101468418  protein Wnt-5a [KO:K00444]
101474169  wnt6; protein Wnt-6 [KO:K00445]
101469419  protein Wnt-7b isoform X1 [KO:K00572]
101466313  protein Wnt-7a [KO:K00572]
101484715  protein Wnt-7a [KO:K00572]
101464816  protein Wnt-7b [KO:K00572]
101464751  protein Wnt-8-like [KO:K00714]
101486602  protein Wnt-8b [KO:K00714]
101466389  protein Wnt-8a-like [KO:K00714]
101472696  wnt9a; protein Wnt-9a [KO:K01064]
101471472  wnt9b; protein Wnt-9b [KO:K01064]
101473879  wnt10a; protein Wnt-10a [KO:K01357]
101464338  wnt10b; protein Wnt-10b [KO:K01357]
101484274  wnt11; protein Wnt-11 [KO:K01384]
101465510  protein Wnt-16 [KO:K01558]
112436275  protein Wnt-16-like [KO:K01558]
101467880  frizzled-7-A [KO:K02432]
101466223  frizzled-1 [KO:K02432]
101473718  frizzled-7-A [KO:K02432]
101477561  fzd2; frizzled-2 [KO:K02235]
101474904  fzd3; frizzled-3 isoform X1 [KO:K02329]
101479845  frizzled-3 isoform X1 [KO:K02329]
101475019  fzd4; frizzled-4 [KO:K02354]
101487122  frizzled-8 [KO:K02375]
101471247  fzd5; frizzled-5 [KO:K02375]
101473776  fzd8; frizzled-8 [KO:K02375]
101472589  fzd6; frizzled-6 isoform X1 [KO:K02376]
101477024  fzd9; frizzled-9 [KO:K02842]
101474735  fzd10; frizzled-10 [KO:K02842]
101483158  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101483250  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
101482854  guanine nucleotide-binding protein subunit alpha-11 isoform X1 [KO:K04634]
101475922  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101473803  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101472481  dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
101468147  dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
101466230  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
101484949  dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
101487930  gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101486082  ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
101475823  catenin beta-1 [KO:K02105]
101469770  tcf7; transcription factor 7 isoform X1 [KO:K02620]
101481605  tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
101466461  transcription factor 7-like 1-B isoform X1 [KO:K04490]
101473558  tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
101472434  transcription factor 7-like 2 [KO:K04491]
101464688  lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
101479983  uncharacterized protein LOC101479983 isoform X1 [KO:K05461]
101465508  kitlg; kit ligand [KO:K05461]
101480857  uncharacterized protein LOC101480857 [KO:K05461]
101477603  mast/stem cell growth factor receptor kita isoform X1 [KO:K05091] [EC:2.7.10.1]
101472356  kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
101474892  hras; GTPase HRas [KO:K02833]
101465888  kras; GTPase KRas isoform X1 [KO:K07827]
101485266  GTPase HRas [KO:K07827]
101470685  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101465184  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101484555  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101478402  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101486997  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101474234  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101480088  tyrosinase [KO:K00505] [EC:1.14.18.1]
101476383  tyrosinase [KO:K00505] [EC:1.14.18.1]
101483045  5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
101463840  tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
101480314  dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
101467161  edn1; endothelin-1 [KO:K16366]
101481778  endothelin receptor type B [KO:K04198]
101475204  ednrb; endothelin receptor type B [KO:K04198]
101478236  endothelin receptor type B-like [KO:K04198]
101487808  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101470797  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101486294  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101481843  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101468881  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101475994  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101474135  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101464832  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101465812  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101478971  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
101468777  calmodulin-like protein 4 isoform X1 [KO:K02183]
101464455  calmodulin [KO:K02183]
101468630  calm3; calmodulin-3 [KO:K02183]
101482160  calmodulin [KO:K02183]
101475860  calm2; calmodulin-2 [KO:K02183]
101468175  LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
101470729  calml4; calmodulin-like protein 4 [KO:K02183]
101466566  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
101480272  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101475499  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515] [EC:2.7.11.17]
101479352  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
101474026  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101473593  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101472930  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
112429915  calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X1 [KO:K04515] [EC:2.7.11.17]
101487097  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101464257  prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101465488  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101478005  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101481445  protein kinase C alpha type-like [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
mze00350  Tyrosine metabolism
mze04010  MAPK signaling pathway
mze04310  Wnt signaling pathway
KO pathway
ko04916   
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