ID   COLI_HUMAN              Reviewed;         267 AA.
AC   P01189; P78442; Q53T23; Q9UD39; Q9UD40;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 2.
DT   13-FEB-2019, entry version 201.
DE   RecName: Full=Pro-opiomelanocortin;
DE            Short=POMC;
DE   AltName: Full=Corticotropin-lipotropin;
DE   Contains:
DE     RecName: Full=NPP;
DE   Contains:
DE     RecName: Full=Melanotropin gamma;
DE     AltName: Full=Gamma-MSH;
DE   Contains:
DE     RecName: Full=Potential peptide;
DE   Contains:
DE     RecName: Full=Corticotropin;
DE     AltName: Full=Adrenocorticotropic hormone;
DE              Short=ACTH;
DE   Contains:
DE     RecName: Full=Melanocyte-stimulating hormone alpha;
DE              Short=Alpha-MSH;
DE     AltName: Full=Melanotropin alpha;
DE   Contains:
DE     RecName: Full=Corticotropin-like intermediary peptide;
DE              Short=CLIP;
DE   Contains:
DE     RecName: Full=Lipotropin beta;
DE     AltName: Full=Beta-LPH;
DE   Contains:
DE     RecName: Full=Lipotropin gamma;
DE     AltName: Full=Gamma-LPH;
DE   Contains:
DE     RecName: Full=Melanocyte-stimulating hormone beta;
DE              Short=Beta-MSH;
DE     AltName: Full=Melanotropin beta;
DE   Contains:
DE     RecName: Full=Beta-endorphin;
DE   Contains:
DE     RecName: Full=Met-enkephalin;
DE   Flags: Precursor;
GN   Name=POMC;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6274691; DOI=10.1016/0014-5793(81)80952-0;
RA   Takahashi H., Teranishi Y., Nakanishi S., Numa S.;
RT   "Isolation and structural organization of the human corticotropin-
RT   beta-lipotropin precursor gene.";
RL   FEBS Lett. 135:97-102(1981).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6299668; DOI=10.1089/dna.1.1982.1.133;
RA   Whitfeld P.L., Seeburg P.H., Shine J.;
RT   "The human pro-opiomelanocortin gene: organization, sequence, and
RT   interspersion with repetitive DNA.";
RL   DNA 1:133-143(1982).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6314261; DOI=10.1093/nar/11.19.6847;
RA   Takahashi H., Hakamata Y., Watanabe Y., Kikuno R., Miyata T., Numa S.;
RT   "Complete nucleotide sequence of the human corticotropin-beta-
RT   lipotropin precursor gene.";
RL   Nucleic Acids Res. 11:6847-6858(1983).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pituitary;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-267.
RX   PubMed=3606677;
RA   Golovin S.Y., Karginov V.A., Bondar A.A., Beklemishev A.B.,
RA   Chekhranova M.K., Mertvetsov N.P., Pankov Y.A.;
RT   "Synthesis, cloning and primary structure of DNA complementary to mRNA
RT   for human pituitary pro-opiomelanocortin.";
RL   Bioorg. Khim. 13:562-564(1987).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 46-267.
RX   PubMed=6254047; DOI=10.1073/pnas.77.8.4890;
RA   Chang A.C.Y., Cochet M., Cohen S.N.;
RT   "Structural organization of human genomic DNA encoding the pro-
RT   opiomelanocortin peptide.";
RL   Proc. Natl. Acad. Sci. U.S.A. 77:4890-4894(1980).
RN   [9]
RP   PROTEIN SEQUENCE OF 27-102.
RX   PubMed=6945581; DOI=10.1073/pnas.78.7.4236;
RA   Seidah N.G., Chretien M.;
RT   "Complete amino acid sequence of a human pituitary glycopeptide: an
RT   important maturation product of pro-opiomelanocortin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:4236-4240(1981).
RN   [10]
RP   PROTEIN SEQUENCE OF 27-102.
RX   PubMed=6267033;
RA   Seidah N.G., Rochemont J., Hamelin J., Lis M., Chretien M.;
RT   "Primary structure of the major human pituitary pro-opiomelanocortin
RT   NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating
RT   activity.";
RL   J. Biol. Chem. 256:7977-7984(1981).
RN   [11]
RP   PROTEIN SEQUENCE OF 105-134, AND AMIDATION AT GLU-134.
RX   PubMed=6272808; DOI=10.1016/S0006-291X(81)80190-8;
RA   Seidah N.G., Rochemont J., Hamelin J., Benjannet S., Chretien M.;
RT   "The missing fragment of the pro-sequence of human pro-
RT   opiomelanocortin: sequence and evidence for C-terminal amidation.";
RL   Biochem. Biophys. Res. Commun. 102:710-716(1981).
RN   [12]
RP   PROTEIN SEQUENCE OF 138-176.
RX   PubMed=4352834; DOI=10.1042/bj1330011;
RA   Bennett H.P.J., Lowry P.J., McMartin C.;
RT   "Confirmation of the 1-20 amino acid sequence of human
RT   adrenocorticotrophin.";
RL   Biochem. J. 133:11-13(1973).
RN   [13]
RP   PROTEIN SEQUENCE OF 138-176.
RX   PubMed=14463577;
RA   Lee T.H., Lerner A.B., Buettner-Janusch V.;
RT   "On the structure of human corticotropin (adrenocorticotropic
RT   hormone).";
RL   J. Biol. Chem. 236:2970-2974(1961).
RN   [14]
RP   PROTEIN SEQUENCE OF 27-41.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [15]
RP   SEQUENCE REVISION (CORTICOTROPIN).
RX   PubMed=4334191;
RA   Riniker B., Sieber P., Rittel W., Zuber H.;
RT   "Revised amino-acid sequences for porcine and human
RT   adrenocorticotrophic hormone.";
RL   Nature New Biol. 235:114-115(1972).
RN   [16]
RP   SYNTHESIS OF CORTICOTROPIN.
RX   PubMed=4338630; DOI=10.1002/hlca.19720550420;
RA   Sieber P., Rittel W., Riniker B.;
RT   "Synthesis of the human adrenal cortex hormone (alpha-h-ACTH) with a
RT   revised amino-acid sequence.";
RL   Helv. Chim. Acta 55:1243-1266(1972).
RN   [17]
RP   SYNTHESIS OF CORTICOTROPIN.
RX   PubMed=4347148; DOI=10.1021/ja00785a049;
RA   Yamashiro D., Li C.H.;
RT   "Adrenocorticotropins. 44. Total synthesis of the human hormone by the
RT   solid-phase method.";
RL   J. Am. Chem. Soc. 95:1310-1315(1973).
RN   [18]
RP   PROTEIN SEQUENCE OF 179-267.
RX   PubMed=1264228; DOI=10.1038/260622a0;
RA   Li C.H., Chung D.;
RT   "Primary structure of human beta-lipotropin.";
RL   Nature 260:622-624(1976).
RN   [19]
RP   PROTEIN SEQUENCE OF 217-234.
RA   Harris J.I.;
RT   "Structure of a melanocyte-stimulating hormone from the human
RT   pituitary gland.";
RL   Nature 184:167-169(1959).
RN   [20]
RP   PROTEIN SEQUENCE OF 237-267.
RX   PubMed=195688;
RA   Dragon N., Seidah N.G., Lis M., Routhier R., Chretien M.;
RT   "Primary structure and morphine-like activity of human beta-
RT   endorphin.";
RL   Can. J. Biochem. 55:666-670(1977).
RN   [21]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 235-256.
RX   PubMed=2424570; DOI=10.1016/0006-8993(86)90896-6;
RA   Bovenberg R.A.L., Burbach J.P.H., Wiegant V.M., Veeneman G.H.,
RA   van Boom J.H., Baas P.D., Jansz H.S., de Wied D.;
RT   "Gamma-endorphin and schizophrenia: amino acid composition of gamma-
RT   endorphin and nucleotide sequence of gamma-endorphin cDNA from
RT   pituitary glands of schizophrenic patients.";
RL   Brain Res. 376:29-37(1986).
RN   [22]
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=2839146; DOI=10.1042/bj2500781;
RA   Fenger M., Johnsen A.H.;
RT   "Alpha-amidated peptides derived from pro-opiomelanocortin in normal
RT   human pituitary.";
RL   Biochem. J. 250:781-788(1988).
RN   [23]
RP   NUCLEOTIDE SEQUENCE OF 75-104, AND VARIANT 97-SER--GLY-99 DEL.
RC   TISSUE=Pituitary;
RX   PubMed=7828531; DOI=10.1210/endo.136.1.7828531;
RA   Morris J.C., Savva D., Lowry P.J.;
RT   "Reduced expression of a naturally deleted form of human
RT   proopiomelanocortin complementary deoxyribonucleic acid after
RT   transfection into Chinese hamster ovary cells.";
RL   Endocrinology 136:195-201(1995).
RN   [24]
RP   INVOLVEMENT IN OBAIRH.
RX   PubMed=9620771; DOI=10.1038/509;
RA   Krude H., Biebermann H., Luck W., Horn R., Brabant G., Grueters A.;
RT   "Severe early-onset obesity, adrenal insufficiency and red hair
RT   pigmentation caused by POMC mutations in humans.";
RL   Nat. Genet. 19:155-157(1998).
RN   [25]
RP   INVOLVEMENT IN ABDOMINAL BODY FAT DISTRIBUTION.
RX   PubMed=16046320; DOI=10.2337/diabetes.54.8.2492;
RA   Baker M., Gaukrodger N., Mayosi B.M., Imrie H., Farrall M.,
RA   Watkins H., Connell J.M.C., Avery P.J., Keavney B.;
RT   "Association between common polymorphisms of the proopiomelanocortin
RT   gene and body fat distribution: a family study.";
RL   Diabetes 54:2492-2496(2005).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pituitary;
RX   PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA   Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT   "Phosphoproteomic analysis of the human pituitary.";
RL   Pituitary 9:109-120(2006).
RN   [27]
RP   VARIANTS ASN-106; GLY-214 AND 97-SER--GLY-99 DEL.
RX   PubMed=9768693; DOI=10.1210/jcem.83.10.5298;
RA   Hinney A., Becker I., Heibult O., Nottebom K., Schmidt A., Ziegler A.,
RA   Mayer H., Siegfried W., Blum W.F., Remschmidt H., Hebebrand J.;
RT   "Systematic mutation screening of the pro-opiomelanocortin gene:
RT   identification of several genetic variants including three different
RT   insertions, one nonsense and two missense point mutations in probands
RT   of different weight extremes.";
RL   J. Clin. Endocrinol. Metab. 83:3737-3741(1998).
RN   [28]
RP   VARIANT GLN-236.
RX   PubMed=10193875; DOI=10.1038/sj.ijo.0800814;
RA   Echwald S.M., Sorensen T.I., Andersen T., Tybjaerg-Hansen A.,
RA   Clausen J.O., Pedersen O.;
RT   "Mutational analysis of the proopiomelanocortin gene in Caucasians
RT   with early onset obesity.";
RL   Int. J. Obes. Relat. Metab. Disord. 23:293-298(1999).
RN   [29]
RP   VARIANTS THR-7; LEU-9; GLY-236 AND 97-SER--GLY-99 DEL.
RX   PubMed=11244459; DOI=10.1038/sj.ijo.0801485;
RA   del Giudice E.M., Cirillo G., Santoro N., D'Urso L., Carbone M.T.,
RA   Toro R.D., Perrone L.;
RT   "Molecular screening of the proopiomelanocortin (POMC) gene in Italian
RT   obese children: report of three new mutations.";
RL   Int. J. Obes. Relat. Metab. Disord. 25:61-67(2001).
RN   [30]
RP   VARIANT GLY-236, CHARACTERIZATION OF VARIANT GLY-236, AND POSSIBLE
RP   INVOLVEMENT IN OBESITY.
RX   PubMed=12165561; DOI=10.1093/hmg/11.17.1997;
RA   Challis B.G., Pritchard L.E., Creemers J.W.M., Delplanque J.,
RA   Keogh J.M., Luan J., Wareham N.J., Yeo G.S.H., Bhattacharyya S.,
RA   Froguel P., White A., Farooqi I.S., O'Rahilly S.;
RT   "A missense mutation disrupting a dibasic prohormone processing site
RT   in pro-opiomelanocortin (POMC) increases susceptibility to early-onset
RT   obesity through a novel molecular mechanism.";
RL   Hum. Mol. Genet. 11:1997-2004(2002).
CC   -!- FUNCTION: Corticotropin: Stimulates the adrenal glands to release
CC       cortisol.
CC   -!- FUNCTION: Melanocyte-stimulating hormone alpha: Anorexigenic
CC       peptide. Increases the pigmentation of skin by increasing melanin
CC       production in melanocytes.
CC   -!- FUNCTION: Melanocyte-stimulating hormone beta: Increases the
CC       pigmentation of skin by increasing melanin production in
CC       melanocytes.
CC   -!- FUNCTION: Beta-endorphin: Endogenous orexigenic opiate.
CC   -!- FUNCTION: Met-enkephalin: Endogenous opiate.
CC   -!- INTERACTION:
CC       O75031:HSF2BP; NbExp=4; IntAct=EBI-12219503, EBI-7116203;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01193}.
CC       Note=Melanocyte-stimulating hormone alpha and beta-endorphin are
CC       stored in separate granules in hypothalamic POMC neurons,
CC       suggesting that secretion may be under the control of different
CC       regulatory mechanisms. {ECO:0000250|UniProtKB:P01193}.
CC   -!- TISSUE SPECIFICITY: ACTH and MSH are produced by the pituitary
CC       gland.
CC   -!- PTM: Specific enzymatic cleavages at paired basic residues yield
CC       the different active peptides. {ECO:0000269|PubMed:2839146}.
CC   -!- PTM: O-glycosylated; reducing sugar is probably N-
CC       acetylgalactosamine.
CC   -!- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized
CC       by an increase of body weight beyond the limitation of skeletal
CC       and physical requirements, as the result of excessive accumulation
CC       of body fat. {ECO:0000269|PubMed:12165561}. Note=Disease
CC       susceptibility may be associated with variations affecting the
CC       gene represented in this entry.
CC   -!- DISEASE: Obesity, early-onset, with adrenal insufficiency and red
CC       hair (OBAIRH) [MIM:609734]: An autosomal recessive disorder
CC       characterized by early-onset obesity due to severe hyperphagia,
CC       pigmentary abnormalities, mainly pale skin and red hair, and
CC       secondary hypocortisolism. {ECO:0000269|PubMed:9620771}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- SIMILARITY: Belongs to the POMC family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Melanocyte-stimulating hormone
CC       entry;
CC       URL="https://en.wikipedia.org/wiki/Melanocyte-stimulating_hormone";
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DR   EMBL; M38297; AAA60140.1; -; mRNA.
DR   EMBL; J00292; AAB59621.1; -; Genomic_DNA.
DR   EMBL; J00291; AAB59621.1; JOINED; Genomic_DNA.
DR   EMBL; V01510; CAA24754.1; -; Genomic_DNA.
DR   EMBL; AC012457; AAY24354.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00729.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00730.1; -; Genomic_DNA.
DR   EMBL; BC065832; AAH65832.1; -; mRNA.
DR   EMBL; M25896; AAA35799.1; -; mRNA.
DR   CCDS; CCDS1717.1; -.
DR   PIR; A17229; CTHUP.
DR   RefSeq; NP_000930.1; NM_000939.3.
DR   RefSeq; NP_001030333.1; NM_001035256.2.
DR   RefSeq; NP_001306133.1; NM_001319204.1.
DR   RefSeq; NP_001306134.1; NM_001319205.1.
DR   UniGene; Hs.1897; -.
DR   PDB; 4XNH; X-ray; 2.10 A; F=138-145.
DR   PDB; 4XPD; X-ray; 2.81 A; F=138-145.
DR   PDB; 4Y49; X-ray; 3.95 A; E/K/Q=138-145.
DR   PDBsum; 4XNH; -.
DR   PDBsum; 4XPD; -.
DR   PDBsum; 4Y49; -.
DR   ProteinModelPortal; P01189; -.
DR   SMR; P01189; -.
DR   BioGrid; 111439; 14.
DR   IntAct; P01189; 16.
DR   STRING; 9606.ENSP00000264708; -.
DR   DrugBank; DB01565; Dihydromorphine.
DR   DrugBank; DB01497; Etorphine.
DR   DrugBank; DB00836; Loperamide.
DR   iPTMnet; P01189; -.
DR   PhosphoSitePlus; P01189; -.
DR   BioMuta; POMC; -.
DR   DMDM; 116880; -.
DR   PaxDb; P01189; -.
DR   PeptideAtlas; P01189; -.
DR   PRIDE; P01189; -.
DR   ProteomicsDB; 51343; -.
DR   DNASU; 5443; -.
DR   Ensembl; ENST00000264708; ENSP00000264708; ENSG00000115138.
DR   Ensembl; ENST00000380794; ENSP00000370171; ENSG00000115138.
DR   Ensembl; ENST00000395826; ENSP00000379170; ENSG00000115138.
DR   Ensembl; ENST00000405623; ENSP00000384092; ENSG00000115138.
DR   GeneID; 5443; -.
DR   KEGG; hsa:5443; -.
DR   UCSC; uc002rfy.1; human.
DR   CTD; 5443; -.
DR   DisGeNET; 5443; -.
DR   EuPathDB; HostDB:ENSG00000115138.10; -.
DR   GeneCards; POMC; -.
DR   GeneReviews; POMC; -.
DR   HGNC; HGNC:9201; POMC.
DR   HPA; CAB002762; -.
DR   HPA; HPA046135; -.
DR   HPA; HPA063644; -.
DR   MalaCards; POMC; -.
DR   MIM; 176830; gene.
DR   MIM; 601665; phenotype.
DR   MIM; 609734; phenotype.
DR   neXtProt; NX_P01189; -.
DR   OpenTargets; ENSG00000115138; -.
DR   Orphanet; 71526; Obesity due to pro-opiomelanocortin deficiency.
DR   PharmGKB; PA33526; -.
DR   eggNOG; ENOG410IKR5; Eukaryota.
DR   eggNOG; ENOG410Z5R4; LUCA.
DR   GeneTree; ENSGT00390000016811; -.
DR   HOVERGEN; HBG004341; -.
DR   InParanoid; P01189; -.
DR   KO; K05228; -.
DR   OMA; VMSHFRW; -.
DR   OrthoDB; 1168862at2759; -.
DR   PhylomeDB; P01189; -.
DR   TreeFam; TF333215; -.
DR   Reactome; R-HSA-111885; Opioid Signalling.
DR   Reactome; R-HSA-193048; Androgen biosynthesis.
DR   Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR   Reactome; R-HSA-202040; G-protein activation.
DR   Reactome; R-HSA-209952; Peptide hormone biosynthesis.
DR   Reactome; R-HSA-211976; Endogenous sterols.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-5579031; Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD).
DR   Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR   SIGNOR; P01189; -.
DR   ChiTaRS; POMC; human.
DR   GeneWiki; Proopiomelanocortin; -.
DR   GenomeRNAi; 5443; -.
DR   PMAP-CutDB; P01189; -.
DR   PRO; PR:P01189; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000115138; Expressed in 93 organ(s), highest expression level in pituitary gland.
DR   ExpressionAtlas; P01189; baseline and differential.
DR   Genevisible; P01189; HS.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR   GO; GO:0030141; C:secretory granule; ISS:UniProtKB.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IDA:BHF-UCL.
DR   GO; GO:0005179; F:hormone activity; IMP:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IMP:UniProtKB.
DR   GO; GO:0070996; F:type 1 melanocortin receptor binding; IDA:BHF-UCL.
DR   GO; GO:0031781; F:type 3 melanocortin receptor binding; IPI:BHF-UCL.
DR   GO; GO:0031782; F:type 4 melanocortin receptor binding; IPI:BHF-UCL.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; IMP:UniProtKB.
DR   GO; GO:0033059; P:cellular pigmentation; IMP:UniProtKB.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; IMP:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0031640; P:killing of cells of other organism; IDA:UniProtKB.
DR   GO; GO:0035821; P:modification of morphology or physiology of other organism; IMP:UniProtKB.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0070965; P:positive regulation of neutrophil mediated killing of fungus; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0032098; P:regulation of appetite; IMP:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR   GO; GO:2000852; P:regulation of corticosterone secretion; IBA:GO_Central.
DR   GO; GO:0070873; P:regulation of glycogen metabolic process; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR   InterPro; IPR013531; Mcrtin_ACTH_cent.
DR   InterPro; IPR013593; Melanocortin_N.
DR   InterPro; IPR013532; Opioid_neuropept.
DR   InterPro; IPR001941; PMOC.
DR   Pfam; PF00976; ACTH_domain; 3.
DR   Pfam; PF08384; NPP; 1.
DR   Pfam; PF08035; Op_neuropeptide; 1.
DR   PRINTS; PR00383; MELANOCORTIN.
DR   SMART; SM01363; ACTH_domain; 2.
DR   SMART; SM01364; NPP; 1.
DR   SMART; SM01365; Op_neuropeptide; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Amidation;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Endorphin; Glycoprotein;
KW   Hormone; Obesity; Phosphoprotein; Polymorphism; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL        1     26       {ECO:0000269|PubMed:15340161,
FT                                ECO:0000269|PubMed:6267033,
FT                                ECO:0000269|PubMed:6945581}.
FT   PEPTIDE      27    102       NPP.
FT                                /FTId=PRO_0000024966.
FT   PEPTIDE      77     87       Melanotropin gamma.
FT                                {ECO:0000269|PubMed:2839146}.
FT                                /FTId=PRO_0000024967.
FT   PEPTIDE     105    134       Potential peptide.
FT                                /FTId=PRO_0000024968.
FT   PEPTIDE     138    176       Corticotropin.
FT                                /FTId=PRO_0000024969.
FT   PEPTIDE     138    150       Melanocyte-stimulating hormone alpha.
FT                                /FTId=PRO_0000024970.
FT   PEPTIDE     156    176       Corticotropin-like intermediary peptide.
FT                                /FTId=PRO_0000024971.
FT   PEPTIDE     179    267       Lipotropin beta.
FT                                /FTId=PRO_0000024972.
FT   PEPTIDE     179    234       Lipotropin gamma.
FT                                /FTId=PRO_0000024973.
FT   PEPTIDE     217    234       Melanocyte-stimulating hormone beta.
FT                                /FTId=PRO_0000024974.
FT   PEPTIDE     237    267       Beta-endorphin.
FT                                /FTId=PRO_0000024975.
FT   PEPTIDE     237    241       Met-enkephalin.
FT                                /FTId=PRO_0000024976.
FT   MOD_RES      87     87       Phenylalanine amide. {ECO:0000250}.
FT   MOD_RES     134    134       Glutamic acid 1-amide.
FT                                {ECO:0000269|PubMed:6272808}.
FT   MOD_RES     138    138       N-acetylserine; in Corticotropin.
FT                                {ECO:0000250|UniProtKB:P01191}.
FT   MOD_RES     150    150       Valine amide. {ECO:0000250}.
FT   MOD_RES     168    168       Phosphoserine.
FT                                {ECO:0000244|PubMed:16807684}.
FT   CARBOHYD     71     71       O-linked (HexNAc...) threonine.
FT                                {ECO:0000269|PubMed:6267033}.
FT   CARBOHYD     91     91       N-linked (GlcNAc...) asparagine.
FT   DISULFID     28     50       {ECO:0000250}.
FT   VARIANT       7      7       S -> T. {ECO:0000269|PubMed:11244459}.
FT                                /FTId=VAR_010699.
FT   VARIANT       9      9       S -> L (in dbSNP:rs139750421).
FT                                {ECO:0000269|PubMed:11244459}.
FT                                /FTId=VAR_010700.
FT   VARIANT      62     62       P -> L (in dbSNP:rs28932471).
FT                                /FTId=VAR_029762.
FT   VARIANT      97     99       Missing. {ECO:0000269|PubMed:11244459,
FT                                ECO:0000269|PubMed:7828531,
FT                                ECO:0000269|PubMed:9768693}.
FT                                /FTId=VAR_010714.
FT   VARIANT     106    106       D -> N (in dbSNP:rs750136455).
FT                                {ECO:0000269|PubMed:9768693}.
FT                                /FTId=VAR_010715.
FT   VARIANT     132    132       P -> A (in dbSNP:rs8192606).
FT                                /FTId=VAR_029314.
FT   VARIANT     214    214       E -> G (in dbSNP:rs80326661).
FT                                {ECO:0000269|PubMed:9768693}.
FT                                /FTId=VAR_010716.
FT   VARIANT     236    236       R -> G (may confer susceptibility to
FT                                obesity; reduces the ability to activate
FT                                melanocortin receptor 4;
FT                                dbSNP:rs28932472).
FT                                {ECO:0000269|PubMed:11244459,
FT                                ECO:0000269|PubMed:12165561}.
FT                                /FTId=VAR_010701.
FT   VARIANT     236    236       R -> Q. {ECO:0000269|PubMed:10193875}.
FT                                /FTId=VAR_012201.
FT   CONFLICT     48     48       R -> G (in Ref. 8). {ECO:0000305}.
FT   CONFLICT    115    115       P -> T (in Ref. 2). {ECO:0000305}.
SQ   SEQUENCE   267 AA;  29424 MW;  B927323474A67536 CRC64;
     MPRSCCSRSG ALLLALLLQA SMEVRGWCLE SSQCQDLTTE SNLLECIRAC KPDLSAETPM
     FPGNGDEQPL TENPRKYVMG HFRWDRFGRR NSSSSGSSGA GQKREDVSAG EDCGPLPEGG
     PEPRSDGAKP GPREGKRSYS MEHFRWGKPV GKKRRPVKVY PNGAEDESAE AFPLEFKREL
     TGQRLREGDG PDGPADDGAG AQADLEHSLL VAAEKKDEGP YRMEHFRWGS PPKDKRYGGF
     MTSEKSQTPL VTLFKNAIIK NAYKKGE
//