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 10-JUN-2026, entry version 238. 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 {ECO:0000303|PubMed:8396929}; DE Contains: DE RecName: Full=Potential peptide; DE Contains: DE RecName: Full=Corticotropin; DE AltName: Full=Adrenocorticotropic hormone {ECO:0000303|PubMed:8396929}; DE Short=ACTH {ECO:0000303|PubMed:8396929}; DE Contains: DE RecName: Full=Melanocyte-stimulating hormone alpha {ECO:0000303|PubMed:8396929}; DE Short=Alpha-MSH {ECO:0000303|PubMed:8396929}; 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 {ECO:0000303|PubMed:8396929}; 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 {ECO:0000312|HGNC:HGNC:9201}; 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; DOI=10.1016/s0021-9258(19)76412-6; 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 FUNCTION (ACTH; ALPHA-MSH; BETA-MSH AND GAMMA-MSH). RC TISSUE=Placenta; RX PubMed=8396929; DOI=10.1006/bbrc.1993.2125; RA Chhajlani V., Muceniece R., Wikberg J.E.S.; RT "Molecular cloning of a novel human melanocortin receptor."; RL Biochem. Biophys. Res. Commun. 195:866-873(1993). RN [25] RP FUNCTION (ACTH; ALPHA-MSH; BETA-MSH AND GAMMA-MSH). RX PubMed=8463333; DOI=10.1016/s0021-9258(18)53088-x; RA Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G., RA Watson S.J., Delvalle J., Yamada T.; RT "Molecular cloning of a novel melanocortin receptor."; RL J. Biol. Chem. 268:8246-8250(1993). RN [26] RP FUNCTION (ACTH; ALPHA-MSH; BETA-MSH AND GAMMA-MSH). RX PubMed=8392067; DOI=10.1016/s0021-9258(18)82452-8; RA Gantz I., Miwa H., Konda Y., Shimoto Y., Tashiro T., Waston S.J., RA Delvalle J.; RT "Molecular cloning, expression, and gene localization of a fourth RT melanocortin receptor."; RL J. Biol. Chem. 268:15174-15179(1993). RN [27] RP FUNCTION (ACTH). RX PubMed=8636348; DOI=10.1210/jcem.81.4.8636348; RA Naville D., Barjhoux L., Jaillard C., Faury D., Despert F., Esteva B., RA Durand P., Saez J.M., Begeot M.; RT "Demonstration by transfection studies that mutations in the RT adrenocorticotropin receptor gene are one cause of the hereditary syndrome RT of glucocorticoid deficiency."; RL J. Clin. Endocrinol. Metab. 81:1442-1448(1996). RN [28] RP INVOLVEMENT IN OBAIRH, AND FUNCTION (ACTH AND ALPHA-MSH). 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 [29] RP FUNCTION (ALPHA-MSH). RX PubMed=10403794; DOI=10.1006/bbrc.1999.0935; RA Schioeth H.B., Phillips S.R., Rudzish R., Birch-Machin M.A., RA Wikberg J.E.S., Rees J.L.; RT "Loss of function mutations of the human melanocortin 1 receptor are common RT and are associated with red hair."; RL Biochem. Biophys. Res. Commun. 260:488-491(1999). RN [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] 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: Precursor protein of pituitary hormones that are involved in CC diverse physiological processes, including the regulation of energy CC balance, stress response, immune function and skin pigmentation. CC {ECO:0000269|PubMed:10403794, ECO:0000269|PubMed:8392067, CC ECO:0000269|PubMed:8396929, ECO:0000269|PubMed:8463333, CC ECO:0000269|PubMed:8636348, ECO:0000269|PubMed:9620771}. CC -!- FUNCTION: [Corticotropin]: Functions as a ligand for the melanocortin CC receptors MC1R, MC2R, MC3R and MC5R (PubMed:8396929, PubMed:8463333, CC PubMed:8636348). Activation of MC1R increases melanogenesis in CC melanocytes found in the skin and hair (PubMed:9620771). Binding to CC MC2R stimulates the adrenal glands to secrete cortisol CC (PubMed:8636348). Contributes to the regulation of energy homeostasis CC through activation of MC3R (Probable). Involved in the regulation CC exocrine gland function through MC5R activation (By similarity). CC {ECO:0000250|UniProtKB:P01193, ECO:0000269|PubMed:8396929, CC ECO:0000269|PubMed:8463333, ECO:0000269|PubMed:8636348, CC ECO:0000269|PubMed:9620771, ECO:0000305|PubMed:8463333}. CC -!- FUNCTION: [Melanocyte-stimulating hormone alpha]: Serves as a ligand CC for the melanocortin receptors MC1R, MC3R, MC4R and MC5R CC (PubMed:8392067, PubMed:8396929, PubMed:8463333). Activation of MC1R CC promotes melanogenesis in melanocytes of the skin and hair CC (PubMed:10403794, PubMed:9620771). Contributes to the regulation of CC energy homeostasis through activation of MC3R (Probable). Through MC4R CC activation, functions as an anorexigenic peptide (PubMed:8392067). CC Promotes immunosuppression and involved in the regulation exocrine CC gland function through MC5R activation (By similarity). CC {ECO:0000250|UniProtKB:P01193, ECO:0000269|PubMed:10403794, CC ECO:0000269|PubMed:8392067, ECO:0000269|PubMed:8396929, CC ECO:0000269|PubMed:8463333, ECO:0000269|PubMed:9620771, CC ECO:0000305|PubMed:8463333}. CC -!- FUNCTION: [Melanocyte-stimulating hormone beta]: Functions as a ligand CC for the melanocortin receptors MC1R, MC3R, MC4R and MC5R CC (PubMed:8396929, PubMed:8463333). Activation of MC1R increases CC melanogenesis in melanocytes found in the skin and hair (Probable). CC Contributes to the regulation of energy homeostasis through activation CC of MC3R (Probable). Through MC4R activation, functions as an CC anorexigenic peptide (PubMed:8392067). Involved in the regulation CC exocrine gland function through MC5R activation (By similarity). CC {ECO:0000250|UniProtKB:P01193, ECO:0000269|PubMed:8392067, CC ECO:0000269|PubMed:8396929, ECO:0000269|PubMed:8463333, CC ECO:0000305|PubMed:8463333}. CC -!- FUNCTION: [Melanotropin gamma]: Functions as a ligand for the CC melanocortin receptors MC1R, MC3R, MC4R and MC5R (PubMed:8396929, CC PubMed:8463333). Activation of MC1R increases melanogenesis in CC melanocytes found in the skin and hair (Probable). Contributes to the CC regulation of energy homeostasis through activation of MC3R (Probable). CC Binds to MC4R with low potency (PubMed:8392067). Involved in the CC regulation exocrine gland function through MC5R activation (By CC similarity). {ECO:0000250|UniProtKB:P01193, ECO:0000269|PubMed:8392067, CC ECO:0000269|PubMed:8396929, ECO:0000269|PubMed:8463333, CC ECO:0000305|PubMed:8463333}. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_000939.4. DR RefSeq; NP_001030333.1; NM_001035256.3. DR RefSeq; NP_001306133.1; NM_001319204.2. DR RefSeq; NP_001306134.1; NM_001319205.2. 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 PDB; 8INR; EM; 2.73 A; L=138-150. DR PDB; 8IOC; EM; 2.86 A; L=77-87. DR PDB; 8W8W; EM; 2.90 A; L=138-150. DR PDB; 8W8X; EM; 2.90 A; L=217-234. DR PDB; 8W8Y; EM; 2.90 A; L=77-87. 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 PDBsum; 8INR; -. DR PDBsum; 8IOC; -. DR PDBsum; 8W8W; -. DR PDBsum; 8W8X; -. DR PDBsum; 8W8Y; -. DR AlphaFoldDB; P01189; -. DR BMRB; P01189; -. DR EMDB; EMD-28907; -. DR EMDB; EMD-31456; -. DR EMDB; EMD-35601; -. DR EMDB; EMD-35615; -. DR SMR; P01189; -. DR BioGRID; 111439; 51. DR FunCoup; P01189; 839. DR IntAct; P01189; 24. DR NDEx; IQUERY-CP-POMC; 11 NDEx IQuery Curated Pathways. 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; 2431 antibodies from 44 providers. DR DNASU; 5443; -. DR Ensembl; ENST00000264708.7; ENSP00000264708.3; ENSG00000115138.12. DR Ensembl; ENST00000380794.5; ENSP00000370171.1; ENSG00000115138.12. DR Ensembl; ENST00000395826.7; ENSP00000379170.2; ENSG00000115138.12. DR Ensembl; ENST00000405623.5; ENSP00000384092.1; ENSG00000115138.12. DR Ensembl; ENST00000942339.1; ENSP00000612398.1; ENSG00000115138.12. 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 ClinPGx; PA33526; -. 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 OpenTargets; ENSG00000115138; -. DR Orphanet; 71526; Obesity due to pro-opiomelanocortin deficiency. 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; 8962839at2759; -. DR PAN-GO; P01189; 4 GO annotations based on evolutionary models. DR PhylomeDB; P01189; -. 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-9856649; Transcriptional and post-translational regulation of MITF-M expression and activity. DR SignaLink; P01189; -. DR SIGNOR; P01189; -. DR Agora; ENSG00000115138; -. 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: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:0106071; P:positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; 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: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 InterPro; IPR050878; POMC-derived_peptides. 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. 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; Proteomics identification; KW 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 121..145 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 222..237 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 81..83 FT /evidence="ECO:0007829|PDB:8IOC" FT STRAND 143..146 FT /evidence="ECO:0007829|PDB:8INR" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:8W8X" FT STRAND 239..245 FT /evidence="ECO:0007829|PDB:6TUB" FT HELIX 246..248 FT /evidence="ECO:0007829|PDB:8F7Q" 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 //