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   27-MAR-2024, entry version 229.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   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-beta-
RT   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-lipotropin
RT   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., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., 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., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., 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., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   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., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., 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 project:
RT   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 for
RT   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; DOI=10.1016/s0021-9258(18)43375-3;
RA   Seidah N.G., Rochemont J., Hamelin J., Lis M., Chretien M.;
RT   "Primary structure of the major human pituitary pro-opiomelanocortin NH2-
RT   terminal glycopeptide. Evidence for an aldosterone-stimulating 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-opiomelanocortin:
RT   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 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 verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [15]
RP   SEQUENCE REVISION (CORTICOTROPIN).
RX   PubMed=4334191; DOI=10.1038/newbio235114b0;
RA   Riniker B., Sieber P., Rittel W., Zuber H.;
RT   "Revised amino-acid sequences for porcine and human adrenocorticotrophic
RT   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 pituitary
RT   gland.";
RL   Nature 184:167-169(1959).
RN   [20]
RP   PROTEIN SEQUENCE OF 237-267.
RX   PubMed=195688; DOI=10.1139/o77-096;
RA   Dragon N., Seidah N.G., Lis M., Routhier R., Chretien M.;
RT   "Primary structure and morphine-like activity of human beta-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 pituitary
RT   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 human
RT   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 transfection
RT   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., Watkins H.,
RA   Connell J.M.C., Avery P.J., Keavney B.;
RT   "Association between common polymorphisms of the proopiomelanocortin gene
RT   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 BY
RP   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 of
RT   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., Clausen J.O.,
RA   Pedersen O.;
RT   "Mutational analysis of the proopiomelanocortin gene in Caucasians with
RT   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., Keogh J.M.,
RA   Luan J., Wareham N.J., Yeo G.S.H., Bhattacharyya S., Froguel P., White A.,
RA   Farooqi I.S., O'Rahilly S.;
RT   "A missense mutation disrupting a dibasic prohormone processing site in
RT   pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity
RT   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 peptide.
CC       Increases the pigmentation of skin by increasing melanin production in
CC       melanocytes.
CC   -!- FUNCTION: [Melanocyte-stimulating hormone beta]: Increases the
CC       pigmentation of skin by increasing melanin production in melanocytes.
CC   -!- FUNCTION: [Beta-endorphin]: Endogenous orexigenic opiate.
CC   -!- FUNCTION: [Met-enkephalin]: Endogenous opiate.
CC   -!- INTERACTION:
CC       P01189; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-12219503, EBI-11096309;
CC       P01189; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-12219503, EBI-8643161;
CC       P01189; Q8N8Y2: ATP6V0D2; NbExp=3; IntAct=EBI-12219503, EBI-3923949;
CC       P01189; Q7RTU4: BHLHA9; NbExp=3; IntAct=EBI-12219503, EBI-17508719;
CC       P01189; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-12219503, EBI-10171570;
CC       P01189; P62508-3: ESRRG; NbExp=3; IntAct=EBI-12219503, EBI-12001340;
CC       P01189; Q8IVS8: GLYCTK; NbExp=3; IntAct=EBI-12219503, EBI-748515;
CC       P01189; Q7Z4H3: HDDC2; NbExp=3; IntAct=EBI-12219503, EBI-6163836;
CC       P01189; O75031: HSF2BP; NbExp=6; IntAct=EBI-12219503, EBI-7116203;
CC       P01189; Q9P2K6: KLHL42; NbExp=3; IntAct=EBI-12219503, EBI-739890;
CC       P01189; Q13064: MKRN3; NbExp=3; IntAct=EBI-12219503, EBI-2340269;
CC       P01189; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-12219503, EBI-10271199;
CC       P01189; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-12219503, EBI-741158;
CC       P01189; Q9UMX2-2: OAZ3; NbExp=3; IntAct=EBI-12219503, EBI-12049527;
CC       P01189; P51687: SUOX; NbExp=3; IntAct=EBI-12219503, EBI-3921347;
CC       P01189; Q99757: TXN2; NbExp=3; IntAct=EBI-12219503, EBI-2932492;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01193}.
CC       Note=Melanocyte-stimulating hormone alpha and beta-endorphin are stored
CC       in separate granules in hypothalamic POMC neurons, suggesting that
CC       secretion may be under the control of different regulatory mechanisms.
CC       {ECO:0000250|UniProtKB:P01193}.
CC   -!- TISSUE SPECIFICITY: ACTH and MSH are produced by the pituitary gland.
CC   -!- PTM: Specific enzymatic cleavages at paired basic residues yield the
CC       different active peptides. {ECO:0000269|PubMed:2839146}.
CC   -!- PTM: O-glycosylated; reducing sugar is probably N-acetylgalactosamine.
CC   -!- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by
CC       an increase of body weight beyond the limitation of skeletal and
CC       physical requirements, as the result of excessive accumulation of body
CC       fat. {ECO:0000269|PubMed:12165561}. Note=Disease susceptibility may be
CC       associated with variants affecting the gene represented in this entry.
CC   -!- DISEASE: Obesity, early-onset, with adrenal insufficiency and red hair
CC       (OBAIRH) [MIM:609734]: An autosomal recessive disorder characterized by
CC       early-onset obesity due to severe hyperphagia, pigmentary
CC       abnormalities, mainly pale skin and red hair, and secondary
CC       hypocortisolism. {ECO:0000269|PubMed:9620771}. Note=The disease is
CC       caused by variants affecting the gene represented in 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   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   PDB; 6TUB; NMR; -; A/B/C/D/E/F=237-267.
DR   PDB; 7F53; EM; 3.00 A; L=138-150.
DR   PDB; 7F54; EM; 3.00 A; L=138-150.
DR   PDB; 7PIV; EM; 2.86 A; P=138-150.
DR   PDB; 8F7Q; EM; 3.22 A; P/Q=237-267.
DR   PDBsum; 4XNH; -.
DR   PDBsum; 4XPD; -.
DR   PDBsum; 4Y49; -.
DR   PDBsum; 6TUB; -.
DR   PDBsum; 7F53; -.
DR   PDBsum; 7F54; -.
DR   PDBsum; 7PIV; -.
DR   PDBsum; 8F7Q; -.
DR   AlphaFoldDB; P01189; -.
DR   BMRB; P01189; -.
DR   EMDB; EMD-31456; -.
DR   SMR; P01189; -.
DR   BioGRID; 111439; 50.
DR   IntAct; P01189; 22.
DR   STRING; 9606.ENSP00000384092; -.
DR   DrugBank; DB01565; Dihydromorphine.
DR   DrugBank; DB01497; Etorphine.
DR   DrugBank; DB00836; Loperamide.
DR   GlyCosmos; P01189; 2 sites, No reported glycans.
DR   GlyGen; P01189; 2 sites.
DR   iPTMnet; P01189; -.
DR   PhosphoSitePlus; P01189; -.
DR   BioMuta; POMC; -.
DR   DMDM; 116880; -.
DR   jPOST; P01189; -.
DR   MassIVE; P01189; -.
DR   PaxDb; 9606-ENSP00000384092; -.
DR   PeptideAtlas; P01189; -.
DR   ProteomicsDB; 51343; -.
DR   Antibodypedia; 3452; 2588 antibodies from 43 providers.
DR   DNASU; 5443; -.
DR   Ensembl; ENST00000264708.7; ENSP00000264708.3; ENSG00000115138.11.
DR   Ensembl; ENST00000380794.5; ENSP00000370171.1; ENSG00000115138.11.
DR   Ensembl; ENST00000395826.7; ENSP00000379170.2; ENSG00000115138.11.
DR   Ensembl; ENST00000405623.5; ENSP00000384092.1; ENSG00000115138.11.
DR   GeneID; 5443; -.
DR   KEGG; hsa:5443; -.
DR   MANE-Select; ENST00000395826.7; ENSP00000379170.2; NM_000939.4; NP_000930.1.
DR   UCSC; uc002rfy.1; human.
DR   AGR; HGNC:9201; -.
DR   CTD; 5443; -.
DR   DisGeNET; 5443; -.
DR   GeneCards; POMC; -.
DR   HGNC; HGNC:9201; POMC.
DR   HPA; ENSG00000115138; Tissue enriched (pituitary).
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   VEuPathDB; HostDB:ENSG00000115138; -.
DR   eggNOG; ENOG502RZNY; Eukaryota.
DR   GeneTree; ENSGT00390000016811; -.
DR   HOGENOM; CLU_094632_0_0_1; -.
DR   InParanoid; P01189; -.
DR   OMA; NIRKYVM; -.
DR   OrthoDB; 3873463at2759; -.
DR   PhylomeDB; P01189; -.
DR   TreeFam; TF333215; -.
DR   PathwayCommons; P01189; -.
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 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   SignaLink; P01189; -.
DR   SIGNOR; P01189; -.
DR   BioGRID-ORCS; 5443; 14 hits in 1155 CRISPR screens.
DR   ChiTaRS; POMC; human.
DR   GeneWiki; Proopiomelanocortin; -.
DR   GenomeRNAi; 5443; -.
DR   Pharos; P01189; Tbio.
DR   PRO; PR:P01189; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P01189; Protein.
DR   Bgee; ENSG00000115138; Expressed in adenohypophysis and 93 other cell types or tissues.
DR   ExpressionAtlas; P01189; baseline and differential.
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: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:0019722; P:calcium-mediated signaling; ISS:ARUK-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; IMP:UniProtKB.
DR   GO; GO:0033059; P:cellular pigmentation; IMP:UniProtKB.
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: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:0043950; P:positive regulation of cAMP-mediated signaling; ISS:ARUK-UCL.
DR   GO; GO:0140668; P:positive regulation of oxytocin production; IEA:Ensembl.
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:1990680; P:response to melanocyte-stimulating hormone; ISS:ARUK-UCL.
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   PANTHER; PTHR11416; PRO-OPIOMELANOCORTIN; 1.
DR   PANTHER; PTHR11416:SF7; PRO-OPIOMELANOCORTIN; 1.
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.
DR   Genevisible; P01189; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Endorphin; Glycoprotein;
KW   Hormone; Obesity; Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000269|PubMed:15340161,
FT                   ECO:0000269|PubMed:6267033, ECO:0000269|PubMed:6945581"
FT   PEPTIDE         27..102
FT                   /note="NPP"
FT                   /id="PRO_0000024966"
FT   PEPTIDE         77..87
FT                   /note="Melanotropin gamma"
FT                   /evidence="ECO:0000269|PubMed:2839146"
FT                   /id="PRO_0000024967"
FT   PEPTIDE         105..134
FT                   /note="Potential peptide"
FT                   /id="PRO_0000024968"
FT   PEPTIDE         138..176
FT                   /note="Corticotropin"
FT                   /id="PRO_0000024969"
FT   PEPTIDE         138..150
FT                   /note="Melanocyte-stimulating hormone alpha"
FT                   /id="PRO_0000024970"
FT   PEPTIDE         156..176
FT                   /note="Corticotropin-like intermediary peptide"
FT                   /id="PRO_0000024971"
FT   PEPTIDE         179..267
FT                   /note="Lipotropin beta"
FT                   /id="PRO_0000024972"
FT   PEPTIDE         179..234
FT                   /note="Lipotropin gamma"
FT                   /id="PRO_0000024973"
FT   PEPTIDE         217..234
FT                   /note="Melanocyte-stimulating hormone beta"
FT                   /id="PRO_0000024974"
FT   PEPTIDE         237..267
FT                   /note="Beta-endorphin"
FT                   /id="PRO_0000024975"
FT   PEPTIDE         237..241
FT                   /note="Met-enkephalin"
FT                   /id="PRO_0000024976"
FT   REGION          88..175
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          181..200
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          222..241
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        127..147
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         87
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         134
FT                   /note="Glutamic acid 1-amide"
FT                   /evidence="ECO:0000269|PubMed:6272808"
FT   MOD_RES         138
FT                   /note="N-acetylserine; in Corticotropin"
FT                   /evidence="ECO:0000250|UniProtKB:P01191"
FT   MOD_RES         150
FT                   /note="Valine amide"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         168
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:16807684"
FT   CARBOHYD        71
FT                   /note="O-linked (HexNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:6267033"
FT   CARBOHYD        91
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   DISULFID        28..50
FT                   /evidence="ECO:0000250"
FT   VARIANT         7
FT                   /note="S -> T"
FT                   /evidence="ECO:0000269|PubMed:11244459"
FT                   /id="VAR_010699"
FT   VARIANT         9
FT                   /note="S -> L (in dbSNP:rs139750421)"
FT                   /evidence="ECO:0000269|PubMed:11244459"
FT                   /id="VAR_010700"
FT   VARIANT         62
FT                   /note="P -> L (in dbSNP:rs28932471)"
FT                   /id="VAR_029762"
FT   VARIANT         97..99
FT                   /note="Missing"
FT                   /evidence="ECO:0000269|PubMed:11244459,
FT                   ECO:0000269|PubMed:7828531, ECO:0000269|PubMed:9768693"
FT                   /id="VAR_010714"
FT   VARIANT         106
FT                   /note="D -> N (in dbSNP:rs750136455)"
FT                   /evidence="ECO:0000269|PubMed:9768693"
FT                   /id="VAR_010715"
FT   VARIANT         132
FT                   /note="P -> A (in dbSNP:rs8192606)"
FT                   /id="VAR_029314"
FT   VARIANT         214
FT                   /note="E -> G (in dbSNP:rs80326661)"
FT                   /evidence="ECO:0000269|PubMed:9768693"
FT                   /id="VAR_010716"
FT   VARIANT         236
FT                   /note="R -> G (may confer susceptibility to obesity;
FT                   reduces the ability to activate melanocortin receptor 4;
FT                   dbSNP:rs28932472)"
FT                   /evidence="ECO:0000269|PubMed:11244459,
FT                   ECO:0000269|PubMed:12165561"
FT                   /id="VAR_010701"
FT   VARIANT         236
FT                   /note="R -> Q"
FT                   /evidence="ECO:0000269|PubMed:10193875"
FT                   /id="VAR_012201"
FT   CONFLICT        48
FT                   /note="R -> G (in Ref. 8)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        115
FT                   /note="P -> T (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   STRAND          143..146
FT                   /evidence="ECO:0007829|PDB:7PIV"
FT   STRAND          239..245
FT                   /evidence="ECO:0007829|PDB:6TUB"
FT   HELIX           249..256
FT                   /evidence="ECO:0007829|PDB:8F7Q"
FT   STRAND          258..263
FT                   /evidence="ECO:0007829|PDB:6TUB"
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
//