KEGG   PATHWAY: lav04916
lav04916                    Pathway                                

Melanogenesis - Loxodonta africana (African savanna elephant)
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
lav04916  Melanogenesis

Loxodonta africana (African savanna elephant) [GN:lav]
100669102  POMC; LOW QUALITY PROTEIN: pro-opiomelanocortin [KO:K05228]
100664659  ASIP; agouti-signaling protein [KO:K08725]
100655206  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100669226  neuroendocrine secretory protein 55-like [KO:K04632]
100671072  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:]
100674724  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
100675525  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
100670244  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:]
100653532  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
100653771  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
100661616  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:]
100663448  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
100675162  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100653565  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100673694  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100666211  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100670574  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
100677344  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
100661096  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:]
100663731  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:]
100668533  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
100653551  WNT2B; protein Wnt-2b [KO:K00182]
100657046  WNT2; protein Wnt-2 [KO:K00182]
100663058  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100662337  WNT3A; protein Wnt-3a [KO:K00312]
100664388  WNT4; LOW QUALITY PROTEIN: protein Wnt-4 [KO:K00408]
100664544  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
100658849  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100675069  WNT6; protein Wnt-6 [KO:K00445]
100675463  WNT7A; protein Wnt-7a [KO:K00572]
100660629  WNT7B; protein Wnt-7b [KO:K00572]
100665788  WNT8B; protein Wnt-8b [KO:K00714]
100668409  WNT8A; protein Wnt-8a [KO:K00714]
100658979  WNT9B; protein Wnt-9b [KO:K01064]
100662057  WNT9A; protein Wnt-9a [KO:K01064]
100674782  WNT10A; protein Wnt-10a [KO:K01357]
100655805  WNT10B; protein Wnt-10b [KO:K01357]
100656630  WNT11; protein Wnt-11 [KO:K01384]
100659037  WNT16; protein Wnt-16 [KO:K01558]
100657335  FZD1; frizzled-1 [KO:K02432]
100658936  FZD7; frizzled-7 [KO:K02432]
100654997  FZD2; frizzled-2 [KO:K02235]
100666465  FZD3; frizzled-3 [KO:K02329]
100675317  FZD4; frizzled-4 [KO:K02354]
100674586  FZD5; frizzled-5 [KO:K02375]
100666499  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
100677440  FZD6; frizzled-6 [KO:K02376]
100660631  FZD10; frizzled-10 [KO:K02842]
100658419  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100656672  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100673586  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100657749  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100657649  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100675105  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:]
100670988  CTNNB1; LOW QUALITY PROTEIN: catenin beta-1 [KO:K02105]
100663559  TCF7; transcription factor 7 isoform X3 [KO:K02620]
100656106  TCF7L2; transcription factor 7-like 2 isoform X22 [KO:K04491]
100658960  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100654759  KITLG; kit ligand isoform X1 [KO:K05461]
100655943  KIT; mast/stem cell growth factor receptor Kit isoform X2 [KO:K05091] [EC:]
100661512  KRAS; GTPase KRas isoform X2 [KO:K07827]
100659051  NRAS; GTPase NRas [KO:K07828]
100655727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
100667623  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100657587  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
100676924  TYR; tyrosinase [KO:K00505] [EC:]
100670218  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
100656003  DCT; L-dopachrome tautomerase [KO:K01827] [EC:]
100672459  EDN1; endothelin-1 isoform X1 [KO:K16366]
100654118  EDNRB; endothelin receptor type B isoform X1 [KO:K04198]
100666344  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100670234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100667957  GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100670617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:]
100672435  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
100668575  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
100663829  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:]
100663507  CALM1; calmodulin-1 [KO:K02183]
100664679  CALM2; calmodulin-2 [KO:K02183]
100657612  calmodulin [KO:K02183]
100669885  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100658962  CALML3; calmodulin-like protein 3 [KO:K02183]
100658208  calmodulin [KO:K02183]
104846071  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:]
100653927  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
100663321  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:]
100658516  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
100665537  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:]
100672078  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:]
100671733  PRKCG; LOW QUALITY PROTEIN: 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)
lav00350  Tyrosine metabolism
lav04010  MAPK signaling pathway
lav04310  Wnt signaling pathway
lav05218  Melanoma
KO pathway

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