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NEU1_HUMAN
ID   NEU1_HUMAN              Reviewed;         125 AA.
AC   P01178; Q3MIG0;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   03-AUG-2022, entry version 190.
DE   RecName: Full=Oxytocin-neurophysin 1;
DE            Short=OT-NPI;
DE   Contains:
DE     RecName: Full=Oxytocin;
DE     AltName: Full=Ocytocin;
DE   Contains:
DE     RecName: Full=Neurophysin 1;
DE   Flags: Precursor;
GN   Name=OXT; Synonyms=OT;
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 [MRNA].
RX   PubMed=3768139; DOI=10.1515/bchm3.1986.367.2.695;
RA   Rehbein M., Hillers M., Mohr E., Ivell R., Morley S., Schmale H.,
RA   Richter D.;
RT   "The neurohypophyseal hormones vasopressin and oxytocin. Precursor
RT   structure, synthesis and regulation.";
RL   Biol. Chem. Hoppe-Seyler 367:695-704(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2991279; DOI=10.1016/s0021-9258(17)39236-0;
RA   Sausville E., Carney D., Battey J.;
RT   "The human vasopressin gene is linked to the oxytocin gene and is
RT   selectively expressed in a cultured lung cancer cell line.";
RL   J. Biol. Chem. 260:10236-10241(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Grunwald W.C. Jr., Cool D.R.;
RT   "Lack of sequence polymorphism in the oxytocin gene of autistic patients.";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 25-110.
RX   PubMed=2249637; DOI=10.1210/endo-127-6-2990;
RA   Ivell R., Furuya K., Brackmann B., Dawood Y., Khan-Dawood F.;
RT   "Expression of the oxytocin and vasopressin genes in human and baboon
RT   gonadal tissues.";
RL   Endocrinology 127:2990-2996(1990).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 80-125.
RX   PubMed=4065330; DOI=10.1016/0014-5793(85)80069-7;
RA   Mohr E., Hillers M., Ivell R., Haulica I.D., Richter D.;
RT   "Expression of the vasopressin and oxytocin genes in human hypothalami.";
RL   FEBS Lett. 193:12-16(1985).
RN   [8]
RP   PROTEIN SEQUENCE OF 32-125.
RX   PubMed=6574452; DOI=10.1073/pnas.80.10.2839;
RA   Chauvet M.-T., Hurpet D., Chauvet J., Acher R.;
RT   "Identification of human neurophysins: complete amino acid sequences of
RT   MSEL- and VLDV-neurophysins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:2839-2843(1983).
RN   [9]
RP   PROTEIN SEQUENCE OF 32-125.
RX   PubMed=7262323; DOI=10.1016/0014-5793(81)80109-3;
RA   Schlesinger D.H., Audhya T.K.;
RT   "A comparative study of mammalian neurophysin protein sequences.";
RL   FEBS Lett. 128:325-328(1981).
RN   [10]
RP   PROTEIN SEQUENCE OF 20-28, AND AMIDATION AT GLY-28.
RX   PubMed=13591312; DOI=10.3181/00379727-98-24154;
RA   Light A., du Vigneaud V.;
RT   "On the nature of oxytocin and vasopressin from human pituitary.";
RL   Proc. Soc. Exp. Biol. Med. 98:692-696(1958).
RN   [11]
RP   FUNCTION OF OXYTOCIN, MUTAGENESIS OF GLY-28, AND SUBUNIT.
RX   PubMed=18174156; DOI=10.1074/jbc.m706477200;
RA   Dutertre S., Croker D., Daly N.L., Andersson A., Muttenthaler M.,
RA   Lumsden N.G., Craik D.J., Alewood P.F., Guillon G., Lewis R.J.;
RT   "Conopressin-T from Conus tulipa reveals an antagonist switch in
RT   vasopressin-like peptides.";
RL   J. Biol. Chem. 283:7100-7108(2008).
CC   -!- FUNCTION: Neurophysin 1 specifically binds oxytocin.
CC   -!- FUNCTION: Oxytocin causes contraction of the smooth muscle of the
CC       uterus and of the mammary gland. Acts by binding to oxytocin receptor
CC       (OXTR) (PubMed:18174156). {ECO:0000269|PubMed:18174156}.
CC   -!- SUBUNIT: Interacts with oxytocin receptor (Ki=1.5 nM)
CC       (PubMed:18174156). Interacts with vasopressin V1aR/AVPR1A (Ki=37 nM),
CC       V1bR/AVPR1B (Ki=222 nM) and V2R/AVPR2 receptors (Ki=823 nM)
CC       (PubMed:18174156). {ECO:0000269|PubMed:18174156}.
CC   -!- INTERACTION:
CC       P01178; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-1762651, EBI-10303987;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PHARMACEUTICAL: Oxytocin is available under the names Pitocin (Parke-
CC       Davis) and Syntocinon (Sandoz). Used to artificially speed or induce
CC       labor.
CC   -!- SIMILARITY: Belongs to the vasopressin/oxytocin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Oxytocin entry;
CC       URL="https://en.wikipedia.org/wiki/Oxytocin";
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DR   EMBL; M25650; AAA59977.1; -; mRNA.
DR   EMBL; M11186; AAA98806.1; -; Genomic_DNA.
DR   EMBL; AY082910; AAL92860.1; -; Genomic_DNA.
DR   EMBL; AL160414; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC069144; AAH69144.1; -; mRNA.
DR   EMBL; BC101841; AAI01842.1; -; mRNA.
DR   EMBL; BC101843; AAI01844.1; -; mRNA.
DR   EMBL; X03173; CAA26936.1; -; mRNA.
DR   EMBL; M62611; AAA59979.1; -; mRNA.
DR   CCDS; CCDS13044.1; -.
DR   PIR; A94676; NFHU1.
DR   RefSeq; NP_000906.1; NM_000915.3.
DR   RefSeq; XP_011527540.1; XM_011529238.1.
DR   PDB; 7OFG; NMR; -; A=20-28.
DR   PDB; 7RYC; EM; 2.90 A; L=20-28.
DR   PDBsum; 7OFG; -.
DR   PDBsum; 7RYC; -.
DR   AlphaFoldDB; P01178; -.
DR   SMR; P01178; -.
DR   BioGRID; 111060; 21.
DR   IntAct; P01178; 7.
DR   STRING; 9606.ENSP00000217386; -.
DR   DrugBank; DB00107; Oxytocin.
DR   DrugCentral; P01178; -.
DR   BioMuta; OXT; -.
DR   DMDM; 128071; -.
DR   MassIVE; P01178; -.
DR   PaxDb; P01178; -.
DR   PeptideAtlas; P01178; -.
DR   PRIDE; P01178; -.
DR   Antibodypedia; 7257; 260 antibodies from 36 providers.
DR   DNASU; 5020; -.
DR   Ensembl; ENST00000217386.2; ENSP00000217386.2; ENSG00000101405.3.
DR   GeneID; 5020; -.
DR   KEGG; hsa:5020; -.
DR   MANE-Select; ENST00000217386.2; ENSP00000217386.2; NM_000915.4; NP_000906.1.
DR   CTD; 5020; -.
DR   DisGeNET; 5020; -.
DR   GeneCards; OXT; -.
DR   HGNC; HGNC:8528; OXT.
DR   HPA; ENSG00000101405; Tissue enriched (brain).
DR   MIM; 167050; gene.
DR   neXtProt; NX_P01178; -.
DR   OpenTargets; ENSG00000101405; -.
DR   PharmGKB; PA32857; -.
DR   VEuPathDB; HostDB:ENSG00000101405; -.
DR   eggNOG; ENOG502S2CT; Eukaryota.
DR   GeneTree; ENSGT00390000004511; -.
DR   HOGENOM; CLU_125770_1_0_1; -.
DR   InParanoid; P01178; -.
DR   OMA; YIQNCPP; -.
DR   OrthoDB; 1548839at2759; -.
DR   PhylomeDB; P01178; -.
DR   TreeFam; TF333018; -.
DR   PathwayCommons; P01178; -.
DR   Reactome; R-HSA-388479; Vasopressin-like receptors.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   SignaLink; P01178; -.
DR   SIGNOR; P01178; -.
DR   BioGRID-ORCS; 5020; 10 hits in 1068 CRISPR screens.
DR   GeneWiki; Neurophysin_I; -.
DR   GeneWiki; Oxytocin; -.
DR   GenomeRNAi; 5020; -.
DR   Pharos; P01178; Tbio.
DR   PRO; PR:P01178; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P01178; protein.
DR   Bgee; ENSG00000101405; Expressed in oocyte and 102 other tissues.
DR   ExpressionAtlas; P01178; baseline and differential.
DR   Genevisible; P01178; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR   GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR   GO; GO:0005185; F:neurohypophyseal hormone activity; IEA:InterPro.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR   GO; GO:0031855; F:oxytocin receptor binding; IBA:GO_Central.
DR   GO; GO:0042756; P:drinking behavior; IEA:Ensembl.
DR   GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR   GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR   GO; GO:0007625; P:grooming behavior; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; IEA:Ensembl.
DR   GO; GO:0042538; P:hyperosmotic salinity response; IEA:Ensembl.
DR   GO; GO:0060179; P:male mating behavior; IEA:Ensembl.
DR   GO; GO:0002125; P:maternal aggressive behavior; IEA:Ensembl.
DR   GO; GO:0042711; P:maternal behavior; IEA:Ensembl.
DR   GO; GO:0007613; P:memory; IEA:Ensembl.
DR   GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0060455; P:negative regulation of gastric acid secretion; IEA:Ensembl.
DR   GO; GO:0035811; P:negative regulation of urine volume; IEA:Ensembl.
DR   GO; GO:0045777; P:positive regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR   GO; GO:0045925; P:positive regulation of female receptivity; IEA:Ensembl.
DR   GO; GO:0060450; P:positive regulation of hindgut contraction; IEA:Ensembl.
DR   GO; GO:0010701; P:positive regulation of norepinephrine secretion; IEA:Ensembl.
DR   GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl.
DR   GO; GO:0060406; P:positive regulation of penile erection; IEA:Ensembl.
DR   GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl.
DR   GO; GO:0035815; P:positive regulation of renal sodium excretion; IEA:Ensembl.
DR   GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR   GO; GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl.
DR   GO; GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl.
DR   GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl.
DR   GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR   GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR   GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR   GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR   GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:0045472; P:response to ether; IEA:Ensembl.
DR   GO; GO:0032094; P:response to food; IEA:Ensembl.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR   GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR   GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR   GO; GO:0034695; P:response to prostaglandin E; IEA:Ensembl.
DR   GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR   GO; GO:0009744; P:response to sucrose; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0030431; P:sleep; IEA:Ensembl.
DR   GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR   GO; GO:0042713; P:sperm ejaculation; IEA:Ensembl.
DR   Gene3D; 2.60.9.10; -; 1.
DR   InterPro; IPR000981; Neurhyp_horm.
DR   InterPro; IPR036387; Neurhyp_horm_dom_sf.
DR   InterPro; IPR022423; Neurohypophysial_hormone_CS.
DR   PANTHER; PTHR11681; PTHR11681; 1.
DR   Pfam; PF00220; Hormone_4; 1.
DR   Pfam; PF00184; Hormone_5; 1.
DR   PIRSF; PIRSF001815; Nonapeptide_hormone_precursor; 1.
DR   PRINTS; PR00831; NEUROPHYSIN.
DR   SMART; SM00003; NH; 1.
DR   SUPFAM; SSF49606; SSF49606; 1.
DR   PROSITE; PS00264; NEUROHYPOPHYS_HORM; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Hormone; Pharmaceutical;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT   PEPTIDE         20..28
FT                   /note="Oxytocin"
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT                   /id="PRO_0000020495"
FT   CHAIN           32..125
FT                   /note="Neurophysin 1"
FT                   /evidence="ECO:0000269|PubMed:6574452,
FT                   ECO:0000269|PubMed:7262323"
FT                   /id="PRO_0000020496"
FT   MOD_RES         28
FT                   /note="Glycine amide"
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT   DISULFID        20..25
FT   DISULFID        41..85
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        44..58
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        52..75
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        59..65
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        92..104
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        98..116
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   DISULFID        105..110
FT                   /evidence="ECO:0000250|UniProtKB:P01175"
FT   MUTAGEN         28
FT                   /note="G->V: Gain of antagonist activity on V1aR/AVPR1A
FT                   (and loss of agonist activity on this receptor). 310-fold
FT                   decrease in affinity for oxytocin receptor (OXTR), 13-fold
FT                   decrease in affinity for V1aR/AVPR1A, and complete loss of
FT                   affinity for V1bR/AVPR1B and V2R/AVPR2."
FT                   /evidence="ECO:0000269|PubMed:18174156"
FT   CONFLICT        94
FT                   /note="S -> G (in Ref. 6; AAA59979)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        100..101
FT                   /note="VL -> AA (in Ref. 9; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        100
FT                   /note="Missing (in Ref. 2; AAA98806)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        124
FT                   /note="Q -> L (in Ref. 9; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:7OFG"
SQ   SEQUENCE   125 AA;  12722 MW;  C65BB544731A0E7C CRC64;
     MAGPSLACCL LGLLALTSAC YIQNCPLGGK RAAPDLDVRK CLPCGPGGKG RCFGPNICCA
     EELGCFVGTA EALRCQEENY LPSPCQSGQK ACGSGGRCAV LGLCCSPDGC HADPACDAEA
     TFSQR
 
 
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