COLI_HUMAN
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 03-AUG-2022, entry version 220.
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; Q8N8Y2: ATP6V0D2; NbExp=3; IntAct=EBI-12219503, EBI-3923949;
CC P01189; Q7RTU4: BHLHA9; NbExp=3; IntAct=EBI-12219503, EBI-17508719;
CC P01189; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-12219503, EBI-8643161;
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 PDBsum; 4XNH; -.
DR PDBsum; 4XPD; -.
DR PDBsum; 4Y49; -.
DR PDBsum; 6TUB; -.
DR AlphaFoldDB; P01189; -.
DR BMRB; P01189; -.
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 GlyGen; P01189; 2 sites.
DR iPTMnet; P01189; -.
DR PhosphoSitePlus; P01189; -.
DR BioMuta; POMC; -.
DR DMDM; 116880; -.
DR jPOST; P01189; -.
DR MassIVE; P01189; -.
DR PaxDb; P01189; -.
DR PeptideAtlas; P01189; -.
DR PRIDE; P01189; -.
DR ProteomicsDB; 51343; -.
DR Antibodypedia; 3452; 2389 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 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; KMHHFRW; -.
DR OrthoDB; 1168862at2759; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P01189; -.
DR SIGNOR; P01189; -.
DR BioGRID-ORCS; 5443; 14 hits in 1073 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 91 other tissues.
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: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:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another 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:0043950; P:positive regulation of cAMP-mediated signaling; ISS:ARUK-UCL.
DR GO; GO:0070965; P:positive regulation of neutrophil mediated killing of fungus; IDA:UniProtKB.
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 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; 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 239..245
FT /evidence="ECO:0007829|PDB:6TUB"
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
