KEGG   PATHWAY: dre04916
Entry
dre04916                    Pathway                                
Name
Melanogenesis - Danio rerio (zebrafish)
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
dre04916  Melanogenesis
dre04916

Organism
Danio rerio (zebrafish) [GN:dre]
Gene
353221  pomca; proopiomelanocortin a precursor [KO:K05228]
100034412  pomcb; proopiomelanocortin b precursor [KO:K05228]
798574  asip1; agouti signaling protein 1 precursor [KO:K08725]
353151  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
557353  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
569499  adcy1b; adenylate cyclase type 1b [KO:K08041] [EC:4.6.1.1]
557026  adcy1a; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
563724  adcy2a; adenylate cyclase type 2 isoform X3 [KO:K08042] [EC:4.6.1.1]
557902  adcy2b; adenylate cyclase type 2b [KO:K08042] [EC:4.6.1.1]
571825  adcy3a; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
562619  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
570652  adcy6a; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
560807  adcy6b; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
568726  adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
100148976  adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
560719  si:dkey-206f10.1; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
560410  si:ch211-132f19.7; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100333702  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101884360  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
393998  prkacba; protein kinase, cAMP-dependent, catalytic, beta a [KO:K04345] [EC:2.7.11.11]
445076  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
563147  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
564064  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a [KO:K04345] [EC:2.7.11.11]
573207  creb1a; cyclic AMP-responsive element-binding protein 1a [KO:K05870]
406853  creb3l3l; cAMP responsive element binding protein 3-like 3 like [KO:K09048]
553700  creb3l3a; cyclic AMP-responsive element-binding protein 3-like protein 3-A [KO:K09048]
791169  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
338317  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100333318  creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100538072  creb3l3b; cyclic AMP-responsive element-binding protein 3-like protein 3-A isoform X1 [KO:K09048]
559273  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
565612  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
566841  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
567111  crebbpb; CREB binding protein b [KO:K04498] [EC:2.3.1.48]
30080  mitfa; melanocyte inducing transcription factor a isoform 2 [KO:K09455]
114833  mitfb; melanocyte inducing transcription factor b [KO:K09455]
30128  wnt1; protein Wnt-1 precursor [KO:K03209]
359837  wnt2ba; wingless-type MMTV integration site family, member 2Ba [KO:K00182]
556087  wnt2bb; wingless-type MMTV integration site family, member 2Bb [KO:K00182]
30127  wnt2; protein Wnt-2 precursor [KO:K00182]
569420  wnt3; proto-oncogene Wnt-3 [KO:K00312]
60632  wnt3a; protein Wnt-3a precursor [KO:K00312]
30123  wnt4; protein Wnt-4a precursor [KO:K00408]
791993  wnt4b; wingless-type MMTV integration site family, member 4b precursor [KO:K00408]
30105  wnt5b; protein Wnt-5b precursor [KO:K00444]
568191  wnt5a; protein Wnt-5a [KO:K00444]
100332722  wnt6a; protein Wnt-6-like [KO:K00445]
561831  wnt6b; protein Wnt-6 [KO:K00445]
565714  wnt7aa; wingless-type MMTV integration site family, member 7Aa [KO:K00572]
100148840  wnt7bb; protein Wnt-7b isoform X1 [KO:K00572]
563427  wnt7ba; protein Wnt-7b [KO:K00572]
568110  protein Wnt-7a-like [KO:K00572]
30122  wnt8a; protein Wnt-8a ORF1 precursor [KO:K00714]
30144  wnt8b; protein Wnt-8b precursor [KO:K00714]
553976  wnt8-2; protein Wnt-8a ORF2 precursor [KO:K00714]
751644  wnt9a; protein Wnt-9a precursor [KO:K01064]
565677  wnt9b; protein Wnt-9b precursor [KO:K01064]
30308  wnt10b; protein Wnt-10b precursor [KO:K01357]
30171  wnt10a; protein Wnt-10a [KO:K01357]
30283  wnt11; protein Wnt-11 precursor [KO:K01384]
791595  wnt11f2; protein Wnt-11 precursor [KO:K01384]
791563  wnt16; protein Wnt-16 precursor [KO:K01558]
30412  fzd7b; frizzled-7b precursor [KO:K02432]
30369  fzd7a; frizzled-7a precursor [KO:K02432]
557384  fzd1; frizzled-1 precursor [KO:K02432]
30370  fzd2; frizzled-2 precursor [KO:K02235]
565921  fzd3a; frizzled-3a precursor [KO:K02329]
567746  fzd3b; frizzled-3b precursor [KO:K02329]
30363  fzd4; frizzled-4 precursor [KO:K02354]
30364  fzd5; frizzled-5 precursor [KO:K02375]
58073  fzd8a; frizzled-8a precursor [KO:K02375]
58072  fzd8b; frizzled-8b precursor [KO:K02375]
393533  fzd6; frizzled-6 precursor [KO:K02376]
30366  fzd10; frizzled-10 precursor [KO:K02842]
58023  fzd9b; frizzled-9b precursor [KO:K02842]
557447  fzd9a; frizzled-9 [KO:K02842]
393760  gnao1a; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O, a [KO:K04534]
393801  gnao1b; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O, b [KO:K04534]
570108  gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
563953  gna11a; guanine nucleotide-binding protein subunit alpha-11a [KO:K04634]
323630  dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
560032  dvl1b; segment polarity protein dishevelled homolog DVL-1b [KO:K02353]
569863  dvl1a; segment polarity protein dishevelled homolog DVL-1 isoform X4 [KO:K02353]
80972  dvl3a; segment polarity protein dishevelled homolog DVL-3a [KO:K02353]
100149082  dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
30654  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
557882  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b [KO:K03083] [EC:2.7.11.26]
30265  ctnnb1; catenin beta-1 [KO:K02105]
324004  ctnnb2; catenin, beta 2 [KO:K02105]
497649  tcf7; transcription factor 7 [KO:K02620]
30523  tcf7l1a; transcription factor 7-like 1-A [KO:K04490]
30556  tcf7l1b; transcription factor 7-like 1-B [KO:K04490]
30510  tcf7l2; transcription factor 7-like 2 [KO:K04491]
30701  lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
553181  kitlgb; kit ligand b precursor [KO:K05461]
553179  kitlga; kit ligand a precursor [KO:K05461]
30256  kita; mast/stem cell growth factor receptor kita precursor [KO:K05091] [EC:2.7.10.1]
497629  kitb; KIT proto-oncogene, receptor tyrosine kinase b precursor [KO:K05091] [EC:2.7.10.1]
553656  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
550286  hrasa; HRas proto-oncogene, GTPase a [KO:K02833]
445289  kras; GTPase KRas isoform 2 [KO:K07827]
393228  zgc:55558; GTPase KRas [KO:K07827]
30380  nras; GTPase NRas [KO:K07828]
30716  raf1a; Raf-1 proto-oncogene, serine/threonine kinase a [KO:K04366] [EC:2.7.11.1]
557109  raf1b; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
406728  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
563181  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
100002225  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
360144  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
399480  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
30207  tyr; tyrosinase precursor [KO:K00505] [EC:1.14.18.1]
437022  tyrp1b; tyrosinase-related protein 1b precursor [KO:K00506] [EC:1.14.18.-]
100333145  tyrp1a; 5,6-dihydroxyindole-2-carboxylic acid oxidase isoform X1 [KO:K00506] [EC:1.14.18.-]
58074  dct; L-dopachrome tautomerase precursor [KO:K01827] [EC:5.3.3.12]
58032  edn1; endothelin-1 precursor [KO:K16366]
30442  ednrba; endothelin receptor Ba precursor [KO:K04198]
560081  ednrbb; endothelin B receptor [KO:K04198]
393946  gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
327650  gnai2b; guanine nucleotide-binding protein G(i) subunit alpha-2b [KO:K04630]
323509  gnaia; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide a [KO:K04630]
336421  gnai2a; guanine nucleotide-binding protein G(i) subunit alpha-2a [KO:K04630]
100006888  gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100001532  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100537538  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
569376  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100149080  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
407700  plcb4; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
321808  calm3b; calmodulin 3b (phosphorylase kinase, delta) [KO:K02183]
192322  calm2b; calmodulin 2b, (phosphorylase kinase, delta) [KO:K02183]
368217  calm1b; calmodulin-1b [KO:K02183]
406660  calm1a; calmodulin-1a [KO:K02183]
336121  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
327379  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
560151  calml4a; calmodulin-like protein 4a [KO:K02183]
100321746  calml4b; calmodulin-like protein 4 [KO:K02183]
436815  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain [KO:K04515] [EC:2.7.11.17]
445208  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform 1 [KO:K04515] [EC:2.7.11.17]
550436  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2 [KO:K04515] [EC:2.7.11.17]
562064  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 [KO:K04515] [EC:2.7.11.17]
793359  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X26 [KO:K04515] [EC:2.7.11.17]
798222  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X4 [KO:K04515] [EC:2.7.11.17]
791855  camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 [KO:K04515] [EC:2.7.11.17]
497384  prkcaa; protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
100333967  si:ch73-374l24.1; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100006675  prkcba; protein kinase C, beta a [KO:K19662] [EC:2.7.11.13]
393953  prkcbb; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100003514  prkcg; 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
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
dre00350  Tyrosine metabolism
dre04010  MAPK signaling pathway
dre04310  Wnt signaling pathway
KO pathway
ko04916   
LinkDB

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