NPP
Melanotropin gamma
     (Gamma-MSH)
Potential peptide
Corticotropin
     (Adrenocorticotropic hormone)
     (ACTH)
Melanotropin alpha
     (Alpha-MSH)
Corticotropin-like intermediary peptide
     (CLIP)
Lipotropin beta
     (Beta-LPH)
Lipotropin gamma
     (Gamma-LPH)
Melanotropin beta
     (Beta-MSH)
Beta-endorphin
Met-enkephalin

Gene name

Name:

POMC

From

Homo sapiens (Human)

[TaxID: 9606]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1016/0014-5793(81)80952-0; PubMed=6274691 [NCBI, ExPASy, EBI, Israel, Japan] Takahashi H., Teranishi Y., Nakanishi S., Numa S.; "Isolation and structural organization of the human corticotropin-beta-lipotropin precursor gene."; FEBS Lett. 135:97-102(1981).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=6299668 [NCBI, ExPASy, EBI, Israel, Japan] Whitfeld P.L., Seeburg P.H., Shine J.; "The human pro-opiomelanocortin gene: organization, sequence, and interspersion with repetitive DNA."; DNA 1:133-143(1982).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1093/nar/11.19.6847; PubMed=6314261 [NCBI, ExPASy, EBI, Israel, Japan] Takahashi H., Hakamata Y., Watanabe Y., Kikuno R., Miyata T., Numa S.; "Complete nucleotide sequence of the human corticotropin-beta-lipotropin precursor gene."; Nucleic Acids Res. 11:6847-6858(1983).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Pituitary; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	NUCLEOTIDE SEQUENCE [MRNA] OF 6-267. PubMed=3606677 [NCBI, ExPASy, EBI, Israel, Japan] Golovin S.Y., Karginov V.A., Bondar A.A., Beklemishev A.B., Chekhranova M.K., Mertvetsov N.P., Pankov Y.A.; "Synthesis, cloning and primary structure of DNA complementary to mRNA for human pituitary pro-opiomelanocortin."; Bioorg. Khim. 13:562-564(1987).
[6]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 46-267. DOI=10.1073/pnas.77.8.4890; PubMed=6254047 [NCBI, ExPASy, EBI, Israel, Japan] Chang A.C.Y., Cochet M., Cohen S.N.; "Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide."; Proc. Natl. Acad. Sci. U.S.A. 77:4890-4894(1980).
[7]	PROTEIN SEQUENCE OF 27-102. DOI=10.1073/pnas.78.7.4236; PubMed=6945581 [NCBI, ExPASy, EBI, Israel, Japan] Seidah N.G., Chretien M.; "Complete amino acid sequence of a human pituitary glycopeptide: an important maturation product of pro-opiomelanocortin."; Proc. Natl. Acad. Sci. U.S.A. 78:4236-4240(1981).
[8]	PROTEIN SEQUENCE OF 27-102. PubMed=6267033 [NCBI, ExPASy, EBI, Israel, Japan] Seidah N.G., Rochemont J., Hamelin J., Lis M., Chretien M.; "Primary structure of the major human pituitary pro-opiomelanocortin NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating activity."; J. Biol. Chem. 256:7977-7984(1981).
[9]	PROTEIN SEQUENCE OF 105-134. DOI=10.1016/S0006-291X(81)80190-8; PubMed=6272808 [NCBI, ExPASy, EBI, Israel, Japan] Seidah N.G., Rochemont J., Hamelin J., Benjannet S., Chretien M.; "The missing fragment of the pro-sequence of human pro-opiomelanocortin: sequence and evidence for C-terminal amidation."; Biochem. Biophys. Res. Commun. 102:710-716(1981).
[10]	PROTEIN SEQUENCE OF 138-176. PubMed=4352834 [NCBI, ExPASy, EBI, Israel, Japan] Bennett H.P.J., Lowry P.J., McMartin C.; "Confirmation of the 1-20 amino acid sequence of human adrenocorticotrophin."; Biochem. J. 133:11-13(1973).
[11]	PROTEIN SEQUENCE OF 138-176. PubMed=14463577 [NCBI, ExPASy, EBI, Israel, Japan] Lee T.H., Lerner A.B., Buettner-Janusch V.; "On the structure of human corticotropin (adrenocorticotropic hormone)."; J. Biol. Chem. 236:2970-2974(1961).
[12]	PROTEIN SEQUENCE OF 27-41. DOI=10.1110/ps.04682504; PubMed=15340161 [NCBI, ExPASy, EBI, Israel, Japan] Zhang Z., Henzel W.J.; "Signal peptide prediction based on analysis of experimentally verified cleavage sites."; Protein Sci. 13:2819-2824(2004).
[13]	SEQUENCE REVISION (CORTICOTROPIN). PubMed=4334191 [NCBI, ExPASy, EBI, Israel, Japan] Riniker B., Sieber P., Rittel W., Zuber H.; "Revised amino-acid sequences for porcine and human adrenocorticotrophic hormone."; Nature New Biol. 235:114-115(1972).
[14]	SYNTHESIS OF CORTICOTROPIN. DOI=10.1002/hlca.19720550420; PubMed=4338630 [NCBI, ExPASy, EBI, Israel, Japan] Sieber P., Rittel W., Riniker B.; "Synthesis of the human adrenal cortex hormone (alpha-h-ACTH) with a revised amino-acid sequence."; Helv. Chim. Acta 55:1243-1248(1972).
[15]	SYNTHESIS OF CORTICOTROPIN. DOI=10.1021/ja00785a049; PubMed=4347148 [NCBI, ExPASy, EBI, Israel, Japan] Yamashiro D., Li C.H.; "Adrenocorticotropins. 44. Total synthesis of the human hormone by the solid-phase method."; J. Am. Chem. Soc. 95:1310-1315(1973).
[16]	PROTEIN SEQUENCE OF 179-267. DOI=10.1038/260622a0; PubMed=1264228 [NCBI, ExPASy, EBI, Israel, Japan] Li C.H., Chung D.; "Primary structure of human beta-lipotropin."; Nature 260:622-624(1976).
[17]	PROTEIN SEQUENCE OF 217-234. Harris J.I.; "Structure of a melanocyte-stimulating hormone from the human pituitary gland."; Nature 184:167-169(1959).
[18]	PROTEIN SEQUENCE OF 237-267. PubMed=195688 [NCBI, ExPASy, EBI, Israel, Japan] Dragon N., Seidah N.G., Lis M., Routhier R., Chretien M.; "Primary structure and morphine-like activity of human beta-endorphin."; Can. J. Biochem. 55:666-670(1977).
[19]	NUCLEOTIDE SEQUENCE [MRNA] OF 235-256. DOI=10.1016/0006-8993(86)90896-6; PubMed=2424570 [NCBI, ExPASy, EBI, Israel, Japan] Bovenberg R.A.L., Burbach J.P.H., Wiegant V.M., Veeneman G.H., van Boom J.H., Baas P.D., Jansz H.S., de Wied D.; "Gamma-endorphin and schizophrenia: amino acid composition of gamma-endorphin and nucleotide sequence of gamma-endorphin cDNA from pituitary glands of schizophrenic patients."; Brain Res. 376:29-37(1986).
[20]	PROTEOLYTIC PROCESSING. PubMed=2839146 [NCBI, ExPASy, EBI, Israel, Japan] Fenger M., Johnsen A.H.; "Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary."; Biochem. J. 250:781-788(1988).
[21]	NUCLEOTIDE SEQUENCE OF 75-104, AND VARIANT 97-SER--GLY-99 DEL. TISSUE=Pituitary; DOI=10.1210/en.136.1.195; PubMed=7828531 [NCBI, ExPASy, EBI, Israel, Japan] Morris J.C., Savva D., Lowry P.J.; "Reduced expression of a naturally deleted form of human proopiomelanocortin complementary deoxyribonucleic acid after transfection into Chinese hamster ovary cells."; Endocrinology 136:195-201(1995).
[22]	INVOLVEMENT IN PRO-OPIOMELANOCORTININ DEFICIENCY. DOI=10.1038/509; PubMed=9620771 [NCBI, ExPASy, EBI, Israel, Japan] Krude H., Biebermann H., Luck W., Horn R., Brabant G., Grueters A.; "Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans."; Nat. Genet. 19:155-157(1998).
[23]	INVOLVEMENT IN ABDOMINAL BODY FAT DISTRIBUTION. DOI=10.2337/diabetes.54.8.2492; PubMed=16046320 [NCBI, ExPASy, EBI, Israel, Japan] Baker M., Gaukrodger N., Mayosi B.M., Imrie H., Farrall M., Watkins H., Connell J.M.C., Avery P.J., Keavney B.; "Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study."; Diabetes 54:2492-2496(2005).
[24]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND MASS SPECTROMETRY. TISSUE=Pituitary; DOI=10.1007/s11102-006-8916-x; PubMed=16807684 [NCBI, ExPASy, EBI, Israel, Japan] Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.; "Phosphoproteomic analysis of the human pituitary."; Pituitary 9:109-120(2006).
[25]	VARIANTS ASN-106; GLY-214 AND 97-SER--GLY-99 DEL. DOI=10.1210/jc.83.10.3737; PubMed=9768693 [NCBI, ExPASy, EBI, Israel, Japan] Hinney A., Becker I., Heibult O., Nottebom K., Schmidt A., Ziegler A., Mayer H., Siegfried W., Blum W.F., Remschmidt H., Hebebrand J.; "Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes."; J. Clin. Endocrinol. Metab. 83:3737-3741(1998).
[26]	VARIANT GLN-236. DOI=10.1038/sj.ijo.0800814; PubMed=10193875 [NCBI, ExPASy, EBI, Israel, Japan] Echwald S.M., Sorensen T.I., Andersen T., Tybjaerg-Hansen A., Clausen J.O., Pedersen O.; "Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity."; Int. J. Obes. Relat. Metab. Disord. 23:293-298(1999).
[27]	VARIANTS THR-7; LEU-9; GLY-236 AND 97-SER--GLY-99 DEL. DOI=10.1038/sj.ijo.0801485; PubMed=11244459 [NCBI, ExPASy, EBI, Israel, Japan] del Giudice E.M., Cirillo G., Santoro N., D'Urso L., Carbone M.T., Toro R.D., Perrone L.; "Molecular screening of the proopiomelanocortin (POMC) gene in Italian obese children: report of three new mutations."; Int. J. Obes. Relat. Metab. Disord. 25:61-67(2001).
[28]	VARIANT GLY-236, CHARACTERIZATION OF VARIANT GLY-236, AND POSSIBLE INVOLVEMENT IN OBESITY. DOI=10.1093/hmg/11.17.1997; PubMed=12165561 [NCBI, ExPASy, EBI, Israel, Japan] Challis B.G., Pritchard L.E., Creemers J.W.M., Delplanque J., Keogh J.M., Luan J., Wareham N.J., Yeo G.S.H., Bhattacharyya S., Froguel P., White A., Farooqi I.S., O'Rahilly S.; "A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism."; Hum. Mol. Genet. 11:1997-2004(2002).

Comments

FUNCTION: ACTH stimulates the adrenal glands to release cortisol.
FUNCTION: MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes.
FUNCTION: Beta-endorphin and Met-enkephalin are endogenous opiates.
TISSUE SPECIFICITY: ACTH and MSH are produced by the pituitary gland.
PTM: Specific enzymatic cleavages at paired basic residues yield the different active peptides.
PTM: O-glycosylated; reducing sugar is probably N-acetylgalactosamine.
DISEASE: Defects in POMC may be associated with susceptibility to obesity [MIM:601665].
DISEASE: Defects in POMC are the cause of pro-opiomelanocortinin deficiency [MIM:609734]. Affected individuals present early-onset obesity, adrenal insufficiency and red hair.
SIMILARITY: Belongs to the POMC family.
WEB RESOURCE: Name=Wikipedia; Note=Melanocyte-stimulating hormone entry; URL="http://en.wikipedia.org/wiki/Melanocyte-stimulating_hormone";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M38297; AAA60140.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J00292; AAB59621.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J00291; AAB59621.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
V01510; CAA24754.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC065832; AAH65832.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M25896; AAA35799.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00000160; -.

PIR

A17229; CTHUP.

RefSeq

NP_000930.1; -.
NP_001030333.1; -.

UniGene

Hs.1897

3D structure databases

ModBase

P01189.

PTM databases

PhosphoSite

P01189; -.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_3_pathway; Syndecan-3-mediated signaling events.

Reactome

REACT_14797; Signaling by GPCR.

Organism-specific databases

GC02M025295; -.

HIX0029971; -.

HGNC:9201; POMC.

CAB002765; -.

176830; gene. [NCBI / EBI]
601665; phenotype. [NCBI / EBI]
609734; phenotype. [NCBI / EBI]

Orphanet

71526; Obesity due to pro-opiomelanocortin deficiency.

PharmGKB

PA33526; -.

Gene expression databases

P01189; -.

P01189; -.

HS_POMC; -.

ENSG00000115138; Homo sapiens.

Ontologies

GO:0005576;	Cellular component: extracellular region (inferred from electronic annotation from InterPro).
GO:0005625;	Cellular component: soluble fraction (traceable author statement from ProtInc).
GO:0005179;	Molecular function: hormone activity (traceable author statement from ProtInc).
GO:0007267;	Biological process: cell-cell signaling (traceable author statement from ProtInc).
GO:0006091;	Biological process: generation of precursor metabolites and energy (traceable author statement from ProtInc).
GO:0007218;	Biological process: neuropeptide signaling pathway (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001941; Mcortin_ACTH.
IPR013533; Mcortin_ACTH_C.
IPR013531; Mcrtin_ACTH_cent.
IPR013593; Melanocortin_N.
IPR013532; Opioid_neuropept.
Graphical view of domain structure.

PANTHER

PTHR11416; Mcortin_ACTH; 1.

Pfam

PF00976; ACTH_domain; 1.
PF08384; NPP; 1.
PF08035; Op_neuropeptide; 1.
Pfam graphical view of domain structure.

PRINTS

PR00383; MELANOCORTIN.

ProDom

PD003250; Mcortin_ACTH; 1.
[Domain structure / List of seq. sharing at least 1 domain]

Proteomic databases

PRIDE

P01189; -.

Genome annotation databases

Ensembl

ENSG00000115138; Homo sapiens. [Contig view]

GeneID

5443; -.

KEGG

hsa:5443; -.

Phylogenomic databases

HOGENOM

P01189; -.

HOVERGEN

P01189; -.

OMA

P01189; GKKRRPV.

Other

DrugBank

DB00741; Hydrocortisone.
DB00836; Loperamide.
DB01108; Trilostane.

21063; -.

P01189; -.

POMC; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Amidation; Cleavage on pair of basic residues; Direct protein sequencing; Disulfide bond; Endorphin; Glycoprotein; Hormone; Obesity; Phosphoprotein; Polymorphism; Signal.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 26`	`26`
`PEPTIDE`	`27 102`	`76`	`NPP.`	`PRO_0000024966`
`PEPTIDE`	`77 87`	`11`	`Melanotropin gamma.`	`PRO_0000024967`
`PEPTIDE`	`105 134`	`30`	`Potential peptide.`	`PRO_0000024968`
`PEPTIDE`	`138 176`	`39`	`Corticotropin.`	`PRO_0000024969`
`PEPTIDE`	`138 150`	`13`	`Melanotropin alpha.`	`PRO_0000024970`
`PEPTIDE`	`156 176`	`21`	`Corticotropin-like intermediary peptide.`	`PRO_0000024971`
`PEPTIDE`	`179 267`	`89`	`Lipotropin beta.`	`PRO_0000024972`
`PEPTIDE`	`179 234`	`56`	`Lipotropin gamma.`	`PRO_0000024973`
`PEPTIDE`	`217 234`	`18`	`Melanotropin beta.`	`PRO_0000024974`
`PEPTIDE`	`237 267`	`31`	`Beta-endorphin.`	`PRO_0000024975`
`PEPTIDE`	`237 241`	`5`	`Met-enkephalin.`	`PRO_0000024976`
`MOD_RES`	`87 87`		`Phenylalanine amide.`
`MOD_RES`	`134 134`		`Glutamic acid 1-amide.`
`MOD_RES`	`150 150`		`Valine amide.`
`MOD_RES`	`168 168`		`Phosphoserine.`
`CARBOHYD`	`71 71`		`O-linked (HexNAc...).`
`CARBOHYD`	`91 91`		`N-linked (GlcNAc...).`
`DISULFID`	`28 50`		`By similarity.`
`VARIANT`	`7 7`	`1`	`S -> T.`	`VAR_010699`
`VARIANT`	`9 9`	`1`	`S -> L.`	`VAR_010700`
`VARIANT`	`62 62`	`1`	`P -> L (in dbSNP:rs28932471 [NCBI]).`	`VAR_029762`
`VARIANT`	`97 99`	`3`	`Missing.`	`VAR_010714`
`VARIANT`	`106 106`	`1`	`D -> N.`	`VAR_010715`
`VARIANT`	`132 132`	`1`	`P -> A (in dbSNP:rs8192606 [NCBI]).`	`VAR_029314`
`VARIANT`	`214 214`	`1`	`E -> G.`	`VAR_010716`
`VARIANT`	`236 236`	`1`	`R -> G (may confer susceptibility to obesity; reduces the ability to activate melanocortin receptor 4; dbSNP:rs28932472 [NCBI]).`	`VAR_010701`
`VARIANT`	`236 236`	`1`	`R -> Q.`	`VAR_012201`
`CONFLICT`	`48 48`		`R -> G (in Ref. 6).`
`CONFLICT`	`115 115`		`P -> T (in Ref. 2).`

Sequence information

Length: 267 AA [This is the length of the unprocessed precursor]

Molecular weight: 29424 Da [This is the MW of the unprocessed precursor]

CRC64: B927323474A67536 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MPRSCCSRSG ALLLALLLQA SMEVRGWCLE SSQCQDLTTE SNLLECIRAC KPDLSAETPM 

        70         80         90        100        110        120 
FPGNGDEQPL TENPRKYVMG HFRWDRFGRR NSSSSGSSGA GQKREDVSAG EDCGPLPEGG 

       130        140        150        160        170        180 
PEPRSDGAKP GPREGKRSYS MEHFRWGKPV GKKRRPVKVY PNGAEDESAE AFPLEFKREL 

       190        200        210        220        230        240 
TGQRLREGDG PDGPADDGAG AQADLEHSLL VAAEKKDEGP YRMEHFRWGS PPKDKRYGGF 

       250        260 
MTSEKSQTPL VTLFKNAIIK NAYKKGE

P01189 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools