KEGG   PATHWAY: hsa04916Help
Entry
hsa04916                    Pathway                                

Name
Melanogenesis - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Melanogenesis
hsa04916

All organismsOrtholog table
Disease
H00168  
Oculocutaneous albinism (OCA)
H00169  
Ocular albinism
H00170  
Piebaldism
H00646  
Odontoonychodermal dysplasia
H00759  
Waardenburg syndrome (WS)
H00759  
Waardenburg syndrome (WS)
H00823  
ABCD syndrome
H00884  
Familial progressive hyperpigmentation
H00947  
Pilomatricoma
H01187  
Tietz syndrome
Drug
D00073  
Hydroquinone (USP)
D00146  
Corticotropin (USP/INN)
D00284  
Cosyntropin (USAN)
D01227  
Bosentan hydrate (JAN)
D02105  
Tetracosactide acetate (JAN)
D03593  
Corticotropin zinc hydroxide (USP)
D06544  
Corticotropin, repository (USP)
D07538  
Bosentan (INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
5443  
POMC; proopiomelanocortin [KO:K05228]
434  
ASIP; agouti signaling protein [KO:K08725]
4157  
MC1R; melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) [KO:K04199]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
1385  
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
10488  
CREB3; cAMP responsive element binding protein 3 [KO:K09048]
90993  
CREB3L1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
64764  
CREB3L2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
84699  
CREB3L3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
148327  
CREB3L4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
4286  
MITF; microphthalmia-associated transcription factor [KO:K09455]
7471  
WNT1; wingless-type MMTV integration site family, member 1 [KO:K03209]
7472  
WNT2; wingless-type MMTV integration site family member 2 [KO:K00182]
7482  
WNT2B; wingless-type MMTV integration site family, member 2B [KO:K00182]
7473  
WNT3; wingless-type MMTV integration site family, member 3 [KO:K00312]
89780  
WNT3A; wingless-type MMTV integration site family, member 3A [KO:K00312]
54361  
WNT4; wingless-type MMTV integration site family, member 4 [KO:K00408]
7474  
WNT5A; wingless-type MMTV integration site family, member 5A [KO:K00444]
81029  
WNT5B; wingless-type MMTV integration site family, member 5B [KO:K00444]
7475  
WNT6; wingless-type MMTV integration site family, member 6 [KO:K00445]
7476  
WNT7A; wingless-type MMTV integration site family, member 7A [KO:K00572]
7477  
WNT7B; wingless-type MMTV integration site family, member 7B [KO:K00572]
7478  
WNT8A; wingless-type MMTV integration site family, member 8A [KO:K00714]
7479  
WNT8B; wingless-type MMTV integration site family, member 8B [KO:K00714]
7483  
WNT9A; wingless-type MMTV integration site family, member 9A [KO:K01064]
7484  
WNT9B; wingless-type MMTV integration site family, member 9B [KO:K01064]
7480  
WNT10B; wingless-type MMTV integration site family, member 10B [KO:K01357]
80326  
WNT10A; wingless-type MMTV integration site family, member 10A [KO:K01357]
7481  
WNT11; wingless-type MMTV integration site family, member 11 [KO:K01384]
51384  
WNT16; wingless-type MMTV integration site family, member 16 [KO:K01558]
8321  
FZD1; frizzled class receptor 1 [KO:K02432]
8324  
FZD7; frizzled class receptor 7 [KO:K02432]
2535  
FZD2; frizzled class receptor 2 [KO:K02235]
7976  
FZD3; frizzled class receptor 3 [KO:K02329]
8322  
FZD4; frizzled class receptor 4 [KO:K02354]
7855  
FZD5; frizzled class receptor 5 [KO:K02375]
8325  
FZD8; frizzled class receptor 8 [KO:K02375]
8323  
FZD6; frizzled class receptor 6 [KO:K02376]
11211  
FZD10; frizzled class receptor 10 [KO:K02842]
8326  
FZD9; frizzled class receptor 9 [KO:K02842]
2775  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
1857  
DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  
DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  
DVL1; dishevelled segment polarity protein 1 [KO:K02353]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
1499  
CTNNB1; catenin (cadherin-associated protein), beta 1, 88kDa [KO:K02105]
6932  
TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934  
TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [KO:K04491]
51176  
LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
4254  
KITLG; KIT ligand [KO:K05461]
3815  
KIT; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [KO:K05091] [EC:2.7.10.1]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
7299  
TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
7306  
TYRP1; tyrosinase-related protein 1 [KO:K00506] [EC:1.14.18.-]
1638  
DCT; dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
1906  
EDN1; endothelin 1 [KO:K16366]
1910  
EDNRB; endothelin receptor type B [KO:K04198]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
810  
CALML3; calmodulin-like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [KO:K02183]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [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)
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)
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)
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)
Reference
  Authors
Chin L.
  Title
The genetics of malignant melanoma: lessons from mouse and man.
  Journal
Nat Rev Cancer 3:559-70 (2003)
Reference
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
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)
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)
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)
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)
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)
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)
KO pathway
 

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