ID   COLI_BOVIN              Reviewed;         265 AA.
AC   P01190; Q05B64; Q28166; Q28167; Q28168;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-SEP-2026, entry version 174.
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=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   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=221818; DOI=10.1038/278423a0;
RA   Nakanishi S., Inoue A., Kita T., Nakamura M., Chang A.C.Y., Cohen S.N.,
RA   Numa S.;
RT   "Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-
RT   lipotropin precursor.";
RL   Nature 278:423-427(1979).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=6249166; DOI=10.1111/j.1749-6632.1980.tb47270.x;
RA   Cohen S.N., Chang A.C.Y., Nakanishi S., Inoue A., Kita T., Nakamura M.,
RA   Numa S.;
RT   "Studies of cloned DNA encoding the structure for the bovine corticotropin-
RT   beta-lipotropin precursor protein.";
RL   Ann. N. Y. Acad. Sci. 343:415-425(1980).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6263630; DOI=10.1111/j.1432-1033.1981.tb06220.x;
RA   Nakanishi S., Teranishi Y., Watanabe Y., Notake M., Noda M., Kakidani H.,
RA   Jingami H., Numa S.;
RT   "Isolation and characterization of the bovine corticotropin/beta-lipotropin
RT   precursor gene.";
RL   Eur. J. Biochem. 115:429-438(1981).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Hypothalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 75-265.
RA   Rubtsov P.M., Chernov B.K., Gorbulev V.G., Parsadanyan A.S.,
RA   Sverdlova P.S., Chupeeva V.V., Golova Y.B., Batchikova N.V.,
RA   Zhvirblis G.S., Skryabin K.G., Baev A.A.;
RT   "Genetic engineering of peptide hormones.";
RL   Mol. Biol. (Mosk.) 19:226-235(1985).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 132-200.
RX   PubMed=216007; DOI=10.1073/pnas.75.12.6021;
RA   Nakanishi G., Inoue A., Kita T., Numa S., Chang A.C.Y., Cohen S.N.,
RA   Nunberg J., Schimke R.T.;
RT   "Construction of bacterial plasmids that contain the nucleotide sequence
RT   for bovine corticotropin-beta-lipotropin precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 75:6021-6025(1978).
RN   [7]
RP   PROTEIN SEQUENCE OF 77-87, AND AMIDATION AT PHE-87.
RX   PubMed=7274457; DOI=10.1016/0014-5793(81)81081-2;
RA   Boehlen P., Esch F., Shibasaki T., Baird A., Ling N., Guillemin R.;
RT   "Isolation and characterization of a gamma 1-melanotropin-like peptide from
RT   bovine neurointermediate pituitary.";
RL   FEBS Lett. 128:67-70(1981).
RN   [8]
RP   PROTEIN SEQUENCE OF 131-144, AND AMIDATION AT VAL-144.
RX   PubMed=13642798;
RA   Li C.H.;
RT   "The relation of chemical structure to the biologic activity of pituitary
RT   hormones.";
RL   Lab. Invest. 8:574-587(1959).
RN   [9]
RP   PROTEIN SEQUENCE OF 132-170.
RA   Li C.H., Dixon J.S., Chung D.;
RT   "Isolation of melatonin, the pineal gland factor that lightens
RT   melanocytes.";
RL   J. Am. Chem. Soc. 80:2587-2588(1958).
RN   [10]
RP   SEQUENCE REVISION (CORTICOTROPIN).
RX   PubMed=4344689; DOI=10.1016/0006-291x(72)90486-x;
RA   Li C.H.;
RT   "Adrenocorticotropin 45. Revised amino acid sequences for sheep and bovine
RT   hormones.";
RL   Biochem. Biophys. Res. Commun. 49:835-839(1972).
RN   [11]
RP   PROTEIN SEQUENCE OF 173-265.
RA   Pankov Y.A.;
RT   "Primary structure of the bovine beta-lipotropic hormone.";
RL   Vopr. Med. Khim. 19:330-332(1973).
RN   [12]
RP   PROTEIN SEQUENCE OF 215-232.
RA   Geschwind I.I., Li C.H., Barnafi L.;
RT   "The isolation and structure of a melanocyte-stimulating hormone from
RT   bovine pituitary glands.";
RL   J. Am. Chem. Soc. 79:1003-1004(1957).
RN   [13]
RP   PROTEIN SEQUENCE OF 215-232.
RX   PubMed=13348631; DOI=10.1038/178090a0;
RA   Harris J.I., Roos P.;
RT   "Amino-acid sequence of a melanophore-stimulating peptide.";
RL   Nature 178:90-90(1956).
RN   [14]
RP   PROTEIN SEQUENCE OF 235-239.
RX   PubMed=1065904; DOI=10.1073/pnas.73.7.2515;
RA   Simantov R., Snyder S.H.;
RT   "Morphine-like peptides in mammalian brain: isolation, structure
RT   elucidation, and interactions with the opiate receptor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 73:2515-2519(1976).
RN   [15]
RP   GLYCOSYLATION AT THR-71 AND ASN-91, AND DISULFIDE BONDS.
RX   PubMed=4030947; DOI=10.1016/s0021-9673(01)87458-6;
RA   James S., Bennett H.P.J.;
RT   "Use of reversed-phase and ion-exchange batch extraction in the
RT   purification of bovine pituitary peptides.";
RL   J. Chromatogr. A 326:329-338(1985).
RN   [16]
RP   SULFATION AT TYR-200, AND PYROGLUTAMATE FORMATION AT GLU-173.
RX   PubMed=2266117; DOI=10.1016/s0021-9258(18)45680-3;
RA   Bateman A., Solomon S., Bennett H.P.J.;
RT   "Post-translational modification of bovine pro-opiomelanocortin. Tyrosine
RT   sulfation and pyroglutamate formation, a mass spectrometric study.";
RL   J. Biol. Chem. 265:22130-22136(1990).
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:0000250|UniProtKB:P01189}.
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: [Beta-endorphin]: Endogenous orexigenic opiate.
CC   -!- FUNCTION: [Met-enkephalin]: Endogenous opiate.
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.
CC   -!- SIMILARITY: Belongs to the POMC family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA30414.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; V00107; CAA23441.1; -; mRNA.
DR   EMBL; V00107; CAA23440.1; -; mRNA.
DR   EMBL; M25587; AAA30354.1; -; mRNA.
DR   EMBL; J00021; AAB59262.1; -; Genomic_DNA.
DR   EMBL; J00019; AAB59262.1; JOINED; Genomic_DNA.
DR   EMBL; BC122728; AAI22729.1; -; mRNA.
DR   EMBL; M23814; AAA30414.1; ALT_INIT; mRNA.
DR   EMBL; M10723; AAA30718.1; -; mRNA.
DR   PIR; A93206; CTBOP.
DR   RefSeq; NP_776576.1; NM_174151.1.
DR   RefSeq; XP_005212977.1; XM_005212920.3.
DR   AlphaFoldDB; P01190; -.
DR   BMRB; P01190; -.
DR   SMR; P01190; -.
DR   FunCoup; P01190; 604.
DR   STRING; 9913.ENSBTAP00000010386; -.
DR   GlyConnect; P01190; 12 N-Linked glycans (1 site), 4 O-Linked glycans (1 site).
DR   GlyCosmos; P01190; 2 sites, 29 glycans.
DR   GlyGen; P01190; 2 sites.
DR   PaxDb; 9913-ENSBTAP00000010386; -.
DR   Ensembl; ENSBTAT00000010386.3; ENSBTAP00000010386.2; ENSBTAG00000007897.3.
DR   Ensembl; ENSBTAT00085022268; ENSBTAP00085031393; ENSBTAG00085009462.
DR   Ensembl; ENSBTAT00090054367; ENSBTAP00090028294; ENSBTAG00090025889.
DR   GeneID; 281416; -.
DR   KEGG; bta:281416; -.
DR   CTD; 5443; -.
DR   VEuPathDB; HostDB:ENSBTAG00000007897; -.
DR   VGNC; VGNC:33155; POMC.
DR   eggNOG; ENOG502RZNY; Eukaryota.
DR   GeneTree; ENSGT00390000016811; -.
DR   HOGENOM; CLU_094632_0_0_1; -.
DR   InParanoid; P01190; -.
DR   OMA; NIRKYVM; -.
DR   OrthoDB; 8962839at2759; -.
DR   Reactome; R-BTA-111885; Opioid Signalling.
DR   Reactome; R-BTA-193048; Androgen biosynthesis.
DR   Reactome; R-BTA-194002; Glucocorticoid biosynthesis.
DR   Reactome; R-BTA-202040; G-protein activation.
DR   Reactome; R-BTA-209952; Peptide hormone biosynthesis.
DR   Reactome; R-BTA-211976; Endogenous sterols.
DR   Reactome; R-BTA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-BTA-418555; G alpha (s) signalling events.
DR   Reactome; R-BTA-418594; G alpha (i) signalling events.
DR   Proteomes; UP000009136; Chromosome 11.
DR   Bgee; ENSBTAG00000007897; Expressed in neurohypophysis and 100 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR   GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR   GO; GO:0070996; F:type 1 melanocortin receptor binding; IEA:Ensembl.
DR   GO; GO:0031781; F:type 3 melanocortin receptor binding; IEA:Ensembl.
DR   GO; GO:0031782; F:type 4 melanocortin receptor binding; IEA:Ensembl.
DR   GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
DR   GO; GO:0033059; P:cellular pigmentation; IBA:GO_Central.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; IEA:Ensembl.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR   GO; GO:0106071; P:positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
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; IEA:Ensembl.
DR   GO; GO:0032098; P:regulation of appetite; IEA:Ensembl.
DR   GO; GO:1990680; P:response to melanocyte-stimulating hormone; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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; 3.
DR   SMART; SM01364; NPP; 1.
DR   SMART; SM01365; Op_neuropeptide; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Endorphin; Glycoprotein;
KW   Hormone; Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome;
KW   Secreted; Signal; Sulfation.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000250"
FT   PEPTIDE         27..103
FT                   /note="NPP"
FT                   /id="PRO_0000024943"
FT   PEPTIDE         77..87
FT                   /note="Melanotropin gamma"
FT                   /id="PRO_0000024944"
FT   PROPEP          106..129
FT                   /id="PRO_0000024945"
FT   PEPTIDE         132..170
FT                   /note="Corticotropin"
FT                   /id="PRO_0000024946"
FT   PEPTIDE         132..144
FT                   /note="Melanocyte-stimulating hormone alpha"
FT                   /id="PRO_0000024947"
FT   PEPTIDE         150..170
FT                   /note="Corticotropin-like intermediary peptide"
FT                   /id="PRO_0000024948"
FT   PEPTIDE         173..265
FT                   /note="Lipotropin beta"
FT                   /id="PRO_0000024949"
FT   PEPTIDE         173..232
FT                   /note="Lipotropin gamma"
FT                   /id="PRO_0000024950"
FT   PEPTIDE         215..232
FT                   /note="Melanocyte-stimulating hormone beta"
FT                   /id="PRO_0000024951"
FT   PEPTIDE         235..265
FT                   /note="Beta-endorphin"
FT                   /id="PRO_0000024952"
FT   PEPTIDE         235..239
FT                   /note="Met-enkephalin"
FT                   /id="PRO_0000024953"
FT   REGION          89..138
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          209..240
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        118..138
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        210..235
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         87
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:7274457"
FT   MOD_RES         132
FT                   /note="N-acetylserine; in Corticotropin"
FT                   /evidence="ECO:0000250|UniProtKB:P01191"
FT   MOD_RES         144
FT                   /note="Valine amide"
FT                   /evidence="ECO:0000269|PubMed:13642798"
FT   MOD_RES         162
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P01189"
FT   MOD_RES         173
FT                   /note="Pyrrolidone carboxylic acid (Glu); partial"
FT                   /evidence="ECO:0000269|PubMed:2266117"
FT   MOD_RES         200
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:2266117"
FT   CARBOHYD        71
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:4030947"
FT                   /id="CAR_000202"
FT   CARBOHYD        91
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:4030947"
FT                   /id="CAR_000034"
FT   DISULFID        28..50
FT                   /evidence="ECO:0000269|PubMed:4030947"
FT   DISULFID        34..46
FT                   /evidence="ECO:0000269|PubMed:4030947"
FT   CONFLICT        10
FT                   /note="G -> A (in Ref. 2; AAA30354)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        139
FT                   /note="R -> P (in Ref. 2; AAA30354)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        161
FT                   /note="Missing (in Ref. 6; AAA30718)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        188
FT                   /note="Q -> G (in Ref. 11; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        190..191
FT                   /note="ES -> D (in Ref. 6; AAA30718)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        196
FT                   /note="A -> P (in Ref. 2; AAA30354)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   265 AA;  29260 MW;  303E9A0BCB073B3F CRC64;
     MPRLCSSRSG ALLLALLLQA SMEVRGWCLE SSQCQDLTTE SNLLACIRAC KPDLSAETPV
     FPGNGDEQPL TENPRKYVMG HFRWDRFGRR NGSSSSGVGG AAQKREEEVA VGEGPGPRGD
     DAETGPREDK RSYSMEHFRW GKPVGKKRRP VKVYPNGAED ESAQAFPLEF KRELTGERLE
     QARGPEAQAE SAAARAELEY GLVAEAEAEA AEKKDSGPYK MEHFRWGSPP KDKRYGGFMT
     SEKSQTPLVT LFKNAIIKNA HKKGQ
//