ID   NEU2_HUMAN              Reviewed;         164 AA.
AC   P01185; A0AV35; O14935;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 2.
DT   24-JUL-2024, entry version 230.
DE   RecName: Full=Vasopressin-neurophysin 2-copeptin;
DE   AltName: Full=AVP-NPII;
DE   Contains:
DE     RecName: Full=Arg-vasopressin;
DE     AltName: Full=Arginine-vasopressin;
DE   Contains:
DE     RecName: Full=Neurophysin 2;
DE     AltName: Full=Neurophysin-II;
DE   Contains:
DE     RecName: Full=Copeptin;
DE   Flags: Precursor;
GN   Name=AVP; Synonyms=ARVP, VP;
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=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   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT NDI VAL-48.
RX   PubMed=1740104; DOI=10.1002/j.1460-2075.1992.tb05022.x;
RA   Bahnsen U., Oosting P., Swaab D.F., Nahke P., Richter D., Schmale H.;
RT   "A missense mutation in the vasopressin-neurophysin precursor gene
RT   cosegregates with human autosomal dominant neurohypophyseal diabetes
RT   insipidus.";
RL   EMBO J. 11:19-23(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-119.
RC   TISSUE=Lung carcinoma;
RA   Du J., North W.G.;
RT   "A missense mutation in the vasopressin mRNA with human small-cell lung
RT   carcinoma.";
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [6]
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [8]
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   [9]
RP   PROTEIN SEQUENCE OF 32-124.
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   [10]
RP   PROTEIN SEQUENCE OF 126-164.
RX   PubMed=7271787; DOI=10.1016/s0006-291x(81)80258-6;
RA   Seidah N.G., Benjannet S., Chretien M.;
RT   "The complete sequence of a novel human pituitary glycopeptide homologous
RT   to pig posterior pituitary glycopeptide.";
RL   Biochem. Biophys. Res. Commun. 100:901-907(1981).
RN   [11]
RP   FUNCTION, AND INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL
RP   FUNCTION).
RX   PubMed=33713620; DOI=10.1016/j.cell.2021.02.053;
RA   Yeung M.L., Teng J.L.L., Jia L., Zhang C., Huang C., Cai J.P., Zhou R.,
RA   Chan K.H., Zhao H., Zhu L., Siu K.L., Fung S.Y., Yung S., Chan T.M.,
RA   To K.K., Chan J.F., Cai Z., Lau S.K.P., Chen Z., Jin D.Y., Woo P.C.Y.,
RA   Yuen K.Y.;
RT   "Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with
RT   proteins related to the renin-angiotensin system.";
RL   Cell 0:0-0(2021).
RN   [12]
RP   VARIANT NDI THR-19.
RX   PubMed=8370682; DOI=10.1210/jcem.77.3.8370682;
RA   McLeod J.F., Kovacs L., Gaskill M.B., Rittig S., Bradley G.S.,
RA   Robertson G.L.;
RT   "Familial neurohypophyseal diabetes insipidus associated with a signal
RT   peptide mutation.";
RL   J. Clin. Endocrinol. Metab. 77:599A-599G(1993).
RN   [13]
RP   VARIANT NDI GLU-78 DEL.
RX   PubMed=8103767; DOI=10.1210/jcem.77.3.8103767;
RA   Yuasa H., Ito M., Nagasaki H., Oiso Y., Miyamoto S., Sasaki N., Saito H.;
RT   "Glu-47, which forms a salt bridge between neurophysin-II and arginine
RT   vasopressin, is deleted in patients with familial central diabetes
RT   insipidus.";
RL   J. Clin. Endocrinol. Metab. 77:600-604(1993).
RN   [14]
RP   VARIANT NDI THR-19.
RX   PubMed=8514868; DOI=10.1172/jci116494;
RA   Ito M., Oiso Y., Murase T., Kondo K., Saito H., Chinzei T., Racchi M.,
RA   Lively M.O.;
RT   "Possible involvement of inefficient cleavage of preprovasopressin by
RT   signal peptidase as a cause for familial central diabetes insipidus.";
RL   J. Clin. Invest. 91:2565-2571(1993).
RN   [15]
RP   VARIANT NDI LEU-55.
RX   PubMed=8045958; DOI=10.1210/jcem.79.2.8045958;
RA   Repaske D.R., Browning J.E.;
RT   "A de novo mutation in the coding sequence for neurophysin-II (Pro24-->Leu)
RT   is associated with onset and transmission of autosomal dominant
RT   neurohypophyseal diabetes insipidus.";
RL   J. Clin. Endocrinol. Metab. 79:421-427(1994).
RN   [16]
RP   VARIANT NDI TRP-93.
RX   PubMed=7714110; DOI=10.1210/jcem.80.4.7714110;
RA   Nagasaki H., Ito M., Yuasa H., Saito H., Fukase M., Hamada K., Ishikawa E.,
RA   Katakami H., Oiso Y.;
RT   "Two novel mutations in the coding region for neurophysin-II associated
RT   with familial central diabetes insipidus.";
RL   J. Clin. Endocrinol. Metab. 80:1352-1356(1995).
RN   [17]
RP   VARIANTS NDI PHE-17; THR-19; VAL-19; ARG-45; CYS-51; GLY-78; PRO-81;
RP   ARG-88; SER-88; SER-92 AND CYS-96.
RX   PubMed=8554046;
RA   Rittig S., Robertson G.L., Siggaard C., Kovacs L., Gregersen N., Nyborg J.,
RA   Pedersen E.B.;
RT   "Identification of 13 new mutations in the vasopressin-neurophysin II gene
RT   in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes
RT   insipidus.";
RL   Am. J. Hum. Genet. 58:107-117(1996).
RN   [18]
RP   VARIANT NDI VAL-54.
RX   PubMed=9360520; DOI=10.1210/jcem.82.11.4231;
RA   Gagliardi P.C., Bernasconi S., Repaske D.R.;
RT   "Autosomal dominant neurohypophyseal diabetes insipidus associated with a
RT   missense mutation encoding Gly23-->Val in neurophysin II.";
RL   J. Clin. Endocrinol. Metab. 82:3643-3646(1997).
RN   [19]
RP   VARIANT NDI THR-19.
RX   PubMed=9580132; DOI=10.1210/jcem.83.3.4658;
RA   Calvo B., Bilbao J.R., Urrutia I., Eizaguirre J., Gaztambide S.,
RA   Castano L.;
RT   "Identification of a novel nonsense mutation and a missense substitution in
RT   the vasopressin-neurophysin II gene in two Spanish kindreds with familial
RT   neurohypophyseal diabetes insipidus.";
RL   J. Clin. Endocrinol. Metab. 83:995-997(1998).
RN   [20]
RP   VARIANTS NDI PHE-87 AND TYR-92.
RX   PubMed=9814475; DOI=10.1210/jcem.83.11.5278;
RA   Grant F.D., Ahmadi A., Hosley C.M., Majzoub J.A.;
RT   "Two novel mutations of the vasopressin gene associated with familial
RT   diabetes insipidus and identification of an asymptomatic carrier infant.";
RL   J. Clin. Endocrinol. Metab. 83:3958-3964(1998).
RN   [21]
RP   VARIANT NDI LEU-26.
RX   PubMed=10369876; DOI=10.1093/hmg/8.7.1303;
RA   Willcutts M.D., Felner E., White P.C.;
RT   "Autosomal recessive familial neurohypophyseal diabetes insipidus with
RT   continued secretion of mutant weakly active vasopressin.";
RL   Hum. Mol. Genet. 8:1303-1307(1999).
RN   [22]
RP   VARIANT NDI ARG-54.
RX   PubMed=10487710; DOI=10.1210/jcem.84.9.5979;
RA   Calvo B., Bilbao J.R., Rodriguez A., Rodriguez-Arnao M.D., Castano L.;
RT   "Molecular analysis in familial neurohypophyseal diabetes insipidus: early
RT   diagnosis of an asymptomatic carrier.";
RL   J. Clin. Endocrinol. Metab. 84:3351-3354(1999).
RN   [23]
RP   VARIANTS NDI ARG-116 AND GLY-116.
RX   PubMed=11017955;
RA   Abbes A.P., Bruggeman B., van den Akker E.L.T., de Groot M.R.,
RA   Franken A.A.M., Drexhage V.R., Engel H.;
RT   "Identification of two distinct mutations at the same nucleotide position,
RT   concomitantly with a novel polymorphism in the vasopressin-neurophysin II
RT   gene (AVP-NP II) in two Dutch families with familial neurohypophyseal
RT   diabetes insipidus.";
RL   Clin. Chem. 46:1699-1702(2000).
RN   [24]
RP   VARIANT NDI TYR-59.
RX   PubMed=11150885; DOI=10.1159/000023573;
RA   Skordis N., Patsalis P.C., Hettinger J.A., Kontou M., Herakleous E.,
RA   Krishnamani M.R., Phillips J.A. III;
RT   "A novel arginine vasopressin-neurophysin II mutation causes autosomal
RT   dominant neurohypophyseal diabetes insipidus and morphologic pituitary
RT   changes.";
RL   Horm. Res. 53:239-245(2000).
RN   [25]
RP   VARIANT NDI TYR-105.
RX   PubMed=10677561; DOI=10.3892/ijmm.5.3.229;
RA   Fujii H., Iida S., Moriwaki K.;
RT   "Familial neurohypophyseal diabetes insipidus associated with a novel
RT   mutation in the vasopressin-neurophysin II gene.";
RL   Int. J. Mol. Med. 5:229-234(2000).
RN   [26]
RP   VARIANT NDI PRO-97.
RX   PubMed=11748489; DOI=10.1055/s-2001-18994;
RA   Mundschenk J., Rittig S., Siggaard C., Hensen J., Lehnert H.;
RT   "A new mutation of the arginine vasopressin-neurophysin II gene in a family
RT   with autosomal dominant neurohypophyseal diabetes insipidus.";
RL   Exp. Clin. Endocrinol. Diabetes 109:406-409(2001).
RN   [27]
RP   VARIANT NDI GLY-116, AND CHARACTERIZATION OF VARIANT NDI GLY-116.
RX   PubMed=11443218; DOI=10.1210/jcem.86.7.7686;
RA   Nijenhuis M., van den Akker E.L.T., Zalm R., Franken A.A.M., Abbes A.P.,
RA   Engel H., de Wied D., Burbach J.P.H.;
RT   "Familial neurohypophysial diabetes insipidus in a large Dutch kindred:
RT   effect of the onset of diabetes on growth in children and cell biological
RT   defects of the mutant vasopressin prohormone.";
RL   J. Clin. Endocrinol. Metab. 86:3410-3420(2001).
RN   [28]
RP   VARIANT NDI GLY-98.
RX   PubMed=11161827; DOI=10.1006/mgme.2000.3117;
RA   DiMeglio L.A., Gagliardi P.C., Browning J.E., Quigley C.A., Repaske D.R.;
RT   "A missense mutation encoding cys(67) --> gly in neurophysin ii is
RT   associated with early onset autosomal dominant neurohypophyseal diabetes
RT   insipidus.";
RL   Mol. Genet. Metab. 72:39-44(2001).
RN   [29]
RP   VARIANTS NDI ARG-54; TYR-92 AND ARG-105.
RX   PubMed=11980620; DOI=10.1530/eje.0.1460649;
RA   Rutishauser J., Kopp P., Gaskill M.B., Kotlar T.J., Robertson G.L.;
RT   "Clinical and molecular analysis of three families with autosomal dominant
RT   neurohypophyseal diabetes insipidus associated with a novel and recurrent
RT   mutations in the vasopressin-neurophysin II gene.";
RL   Eur. J. Endocrinol. 146:649-656(2002).
RN   [30]
RP   VARIANT NDI SER-92.
RX   PubMed=12012274; DOI=10.1055/s-2002-29091;
RA   Bullmann C., Kotzka J., Grimm T., Heppner C., Jockenhovel F., Krone W.,
RA   Muller-Wieland D.;
RT   "Identification of a novel mutation in the arginine vasopressin-neurophysin
RT   II gene in familial central diabetes insipidus.";
RL   Exp. Clin. Endocrinol. Diabetes 110:134-137(2002).
RN   [31]
RP   VARIANT NDI HIS-21.
RX   PubMed=12107248; DOI=10.1210/jcem.87.7.8677;
RA   Rittig S., Siggaard C., Ozata M., Yetkin I., Gregersen N., Pedersen E.B.,
RA   Robertson G.L.;
RT   "Autosomal dominant neurohypophyseal diabetes insipidus due to substitution
RT   of histidine for tyrosine-2 in the vasopressin moiety of the hormone
RT   precursor.";
RL   J. Clin. Endocrinol. Metab. 87:3351-3355(2002).
RN   [32]
RP   VARIANT NDI PHE-104.
RX   PubMed=12359138; DOI=10.1016/s1096-7192(02)00118-x;
RA   Santiprabhob J., Browning J.E., Repaske D.R.;
RT   "A missense mutation encoding Cys73Phe in neurophysin II is associated with
RT   autosomal dominant neurohypophyseal diabetes insipidus.";
RL   Mol. Genet. Metab. 77:112-118(2002).
RN   [33]
RP   VARIANT NDI THR-19.
RX   PubMed=12519420; DOI=10.1046/j.1365-2265.2003.01667.x;
RA   Boson W.L., Sarubi J.C., D'Alva C.B., Friedman E., Faria D., De Marco L.,
RA   Wajchenberg B.;
RT   "A signal peptide mutation of the arginine vasopressin gene in monozygotic
RT   twins.";
RL   Clin. Endocrinol. (Oxf.) 58:108-110(2003).
RN   [34]
RP   VARIANT NDI PRO-99.
RX   PubMed=14510916; DOI=10.1046/j.1365-2265.2003.01834.x;
RA   Elias P.C.L., Elias L.L.K., Torres N., Moreira A.C., Antunes-Rodrigues J.,
RA   Castro M.;
RT   "Progressive decline of vasopressin secretion in familial autosomal
RT   dominant neurohypophyseal diabetes insipidus presenting a novel mutation in
RT   the vasopressin-neurophysin II gene.";
RL   Clin. Endocrinol. (Oxf.) 59:511-518(2003).
RN   [35]
RP   VARIANT NDI PHE-58.
RX   PubMed=12931042; DOI=10.1159/000072526;
RA   Wolf M.T.F., Doetsch J., Metzler M., Holder M., Repp R., Rascher W.;
RT   "A new missense mutation of the vasopressin-neurophysin II gene in a family
RT   with neurohypophyseal diabetes insipidus.";
RL   Horm. Res. 60:143-147(2003).
RN   [36]
RP   VARIANT NDI SER-98.
RX   PubMed=15538939; DOI=10.1530/eje.0.1510605;
RA   Baglioni S., Corona G., Maggi M., Serio M., Peri A.;
RT   "Identification of a novel mutation in the arginine vasopressin-neurophysin
RT   II gene affecting the sixth intrachain disulfide bridge of the neurophysin
RT   II moiety.";
RL   Eur. J. Endocrinol. 151:605-611(2004).
RN   [37]
RP   VARIANTS NDI THR-19; VAL-19; ARG-54; ALA-67; GLY-78; GLU-78 DEL; ASP-96;
RP   CYS-96; GLY-104 AND TRP-116.
RX   PubMed=14673472; DOI=10.1038/sj.ejhg.5201086;
RA   Christensen J.H., Siggaard C., Corydon T.J., deSanctis L., Kovacs L.,
RA   Robertson G.L., Gregersen N., Rittig S.;
RT   "Six novel mutations in the arginine vasopressin gene in 15 kindreds with
RT   autosomal dominant familial neurohypophyseal diabetes insipidus give
RT   further insight into the pathogenesis.";
RL   Eur. J. Hum. Genet. 12:44-51(2004).
RN   [38]
RP   FUNCTION OF VASOPRESSIN, 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 2]: Specifically binds vasopressin.
CC   -!- FUNCTION: [Arg-vasopressin]: Has a direct antidiuretic action on the
CC       kidney, it also causes vasoconstriction of the peripheral vessels. Acts
CC       by binding to vasopressin receptors (V1bR/AVPR1B, V1aR/AVPR1A, and
CC       V2R/AVPR2) (PubMed:18174156). {ECO:0000269|PubMed:18174156}.
CC   -!- SUBUNIT: Interacts with vasopressin receptors V1bR/AVPR1B (Ki=85 pM),
CC       V1aR/AVPR1A (Ki=0.6 nM) and V2R/AVPR2 (Ki=4.9 nM) (PubMed:18174156).
CC       Interacts with oxytocin receptor (OXTR) (Ki=110 nM) (PubMed:18174156).
CC       {ECO:0000269|PubMed:18174156}.
CC   -!- SUBUNIT: [Arg-vasopressin]: (Microbial infection) May interact with
CC       SARS coronavirus-2/SARS-CoV-2; they may form a complex with secreted
CC       ACE2. {ECO:0000269|PubMed:33713620}.
CC   -!- INTERACTION:
CC       P01185; O43741: PRKAB2; NbExp=3; IntAct=EBI-6858021, EBI-1053424;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- DISEASE: Diabetes insipidus, neurohypophyseal (NDI) [MIM:125700]: A
CC       disease characterized by persistent thirst, polydipsia and polyuria.
CC       Affected individuals are apparently normal at birth, but
CC       characteristically develop symptoms of vasopressin deficiency during
CC       childhood. {ECO:0000269|PubMed:10369876, ECO:0000269|PubMed:10487710,
CC       ECO:0000269|PubMed:10677561, ECO:0000269|PubMed:11017955,
CC       ECO:0000269|PubMed:11150885, ECO:0000269|PubMed:11161827,
CC       ECO:0000269|PubMed:11443218, ECO:0000269|PubMed:11748489,
CC       ECO:0000269|PubMed:11980620, ECO:0000269|PubMed:12012274,
CC       ECO:0000269|PubMed:12107248, ECO:0000269|PubMed:12359138,
CC       ECO:0000269|PubMed:12519420, ECO:0000269|PubMed:12931042,
CC       ECO:0000269|PubMed:14510916, ECO:0000269|PubMed:14673472,
CC       ECO:0000269|PubMed:15538939, ECO:0000269|PubMed:1740104,
CC       ECO:0000269|PubMed:7714110, ECO:0000269|PubMed:8045958,
CC       ECO:0000269|PubMed:8103767, ECO:0000269|PubMed:8370682,
CC       ECO:0000269|PubMed:8514868, ECO:0000269|PubMed:8554046,
CC       ECO:0000269|PubMed:9360520, ECO:0000269|PubMed:9580132,
CC       ECO:0000269|PubMed:9814475}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the vasopressin/oxytocin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Vasopressin entry;
CC       URL="https://en.wikipedia.org/wiki/Vasopressin";
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DR   EMBL; M11166; AAA98772.1; -; Genomic_DNA.
DR   EMBL; M25647; AAA61291.1; -; mRNA.
DR   EMBL; X03172; CAA26935.1; -; mRNA.
DR   EMBL; X62890; CAA44681.1; -; Genomic_DNA.
DR   EMBL; AF031476; AAB86629.1; -; mRNA.
DR   EMBL; AL160414; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; X62891; CAA44682.1; -; Genomic_DNA.
DR   EMBL; BC126196; AAI26197.1; -; mRNA.
DR   EMBL; BC126224; AAI26225.1; -; mRNA.
DR   CCDS; CCDS13045.1; -.
DR   PIR; A39269; A39269.
DR   PIR; B94676; NVHU2.
DR   RefSeq; NP_000481.2; NM_000490.4.
DR   RefSeq; XP_011527569.1; XM_011529267.1.
DR   PDB; 7BB6; EM; 4.20 A; H=20-28.
DR   PDB; 7BB7; EM; 4.40 A; H=20-28.
DR   PDB; 7DW9; EM; 2.60 A; C=20-28.
DR   PDB; 7KH0; EM; 2.80 A; L=20-28.
DR   PDB; 7R0C; EM; 4.73 A; B=20-28.
DR   PDBsum; 7BB6; -.
DR   PDBsum; 7BB7; -.
DR   PDBsum; 7DW9; -.
DR   PDBsum; 7KH0; -.
DR   PDBsum; 7R0C; -.
DR   AlphaFoldDB; P01185; -.
DR   EMDB; EMD-12128; -.
DR   EMDB; EMD-12129; -.
DR   EMDB; EMD-22872; -.
DR   SMR; P01185; -.
DR   BioGRID; 107032; 50.
DR   IntAct; P01185; 21.
DR   STRING; 9606.ENSP00000369647; -.
DR   GlyCosmos; P01185; 1 site, No reported glycans.
DR   GlyGen; P01185; 1 site.
DR   iPTMnet; P01185; -.
DR   PhosphoSitePlus; P01185; -.
DR   BioMuta; AVP; -.
DR   DMDM; 128083; -.
DR   MassIVE; P01185; -.
DR   PaxDb; 9606-ENSP00000369647; -.
DR   PeptideAtlas; P01185; -.
DR   ProteomicsDB; 51342; -.
DR   Antibodypedia; 7264; 348 antibodies from 31 providers.
DR   DNASU; 551; -.
DR   Ensembl; ENST00000380293.3; ENSP00000369647.3; ENSG00000101200.5.
DR   GeneID; 551; -.
DR   KEGG; hsa:551; -.
DR   MANE-Select; ENST00000380293.3; ENSP00000369647.3; NM_000490.5; NP_000481.2.
DR   AGR; HGNC:894; -.
DR   CTD; 551; -.
DR   DisGeNET; 551; -.
DR   GeneCards; AVP; -.
DR   HGNC; HGNC:894; AVP.
DR   HPA; ENSG00000101200; Tissue enriched (brain).
DR   MalaCards; AVP; -.
DR   MIM; 125700; phenotype.
DR   MIM; 192340; gene.
DR   neXtProt; NX_P01185; -.
DR   OpenTargets; ENSG00000101200; -.
DR   Orphanet; 30925; Hereditary arginine vasopressin deficiency.
DR   PharmGKB; PA25186; -.
DR   VEuPathDB; HostDB:ENSG00000101200; -.
DR   eggNOG; ENOG502S21K; Eukaryota.
DR   GeneTree; ENSGT00390000004511; -.
DR   HOGENOM; CLU_125770_0_0_1; -.
DR   InParanoid; P01185; -.
DR   OMA; GCVVDSD; -.
DR   OrthoDB; 5398672at2759; -.
DR   PhylomeDB; P01185; -.
DR   TreeFam; TF333018; -.
DR   PathwayCommons; P01185; -.
DR   Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR   Reactome; R-HSA-388479; Vasopressin-like receptors.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR   Reactome; R-HSA-5619099; Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI).
DR   Reactome; R-HSA-879518; Transport of organic anions.
DR   Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-HSA-9036092; Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI).
DR   SignaLink; P01185; -.
DR   SIGNOR; P01185; -.
DR   BioGRID-ORCS; 551; 17 hits in 1146 CRISPR screens.
DR   GeneWiki; Vasopressin; -.
DR   GenomeRNAi; 551; -.
DR   Pharos; P01185; Tbio.
DR   PRO; PR:P01185; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P01185; Protein.
DR   Bgee; ENSG00000101200; Expressed in hypothalamus and 102 other cell types or tissues.
DR   ExpressionAtlas; P01185; baseline and differential.
DR   GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl.
DR   GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR   GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR   GO; GO:0005185; F:neurohypophyseal hormone activity; IEA:InterPro.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IDA:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR   GO; GO:0031894; F:V1A vasopressin receptor binding; IPI:UniProtKB.
DR   GO; GO:0031895; F:V1B vasopressin receptor binding; IEA:Ensembl.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR   GO; GO:0007625; P:grooming behavior; IEA:Ensembl.
DR   GO; GO:0007626; P:locomotory 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:0050891; P:multicellular organismal-level water homeostasis; IEA:Ensembl.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR   GO; GO:0007621; P:negative regulation of female receptivity; IEA:Ensembl.
DR   GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
DR   GO; GO:0051970; P:negative regulation of transmission of nerve impulse; IEA:Ensembl.
DR   GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0032849; P:positive regulation of cellular pH reduction; IEA:Ensembl.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0014049; P:positive regulation of glutamate secretion; IEA:Ensembl.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Ensembl.
DR   GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IEA:Ensembl.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR   GO; GO:0070528; P:protein kinase C signaling; IDA:UniProtKB.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR   GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR   GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR   GO; GO:0046718; P:symbiont entry into host cell; IDA:UniProtKB.
DR   GO; GO:0042310; P:vasoconstriction; IEA:UniProtKB-KW.
DR   GO; GO:0006833; P:water transport; TAS:ProtInc.
DR   Gene3D; 2.60.9.10; Neurohypophysial hormone domain; 1.
DR   InterPro; IPR000981; Neurhyp_horm.
DR   InterPro; IPR036387; Neurhyp_horm_dom_sf.
DR   InterPro; IPR022423; Neurohypophysial_hormone_CS.
DR   PANTHER; PTHR11681; NEUROPHYSIN; 1.
DR   PANTHER; PTHR11681:SF9; VASOPRESSIN-NEUROPHYSIN 2-COPEPTIN; 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; Neurophysin II; 1.
DR   PROSITE; PS00264; NEUROHYPOPHYS_HORM; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Diabetes insipidus; Direct protein sequencing; Disease variant;
KW   Disulfide bond; Glycoprotein; Hormone; Host-virus interaction;
KW   Reference proteome; Secreted; Signal; Vasoactive; Vasoconstrictor.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT   PEPTIDE         20..28
FT                   /note="Arg-vasopressin"
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT                   /id="PRO_0000020515"
FT   CHAIN           32..124
FT                   /note="Neurophysin 2"
FT                   /evidence="ECO:0000269|PubMed:6574452"
FT                   /id="PRO_0000020516"
FT   PEPTIDE         126..164
FT                   /note="Copeptin"
FT                   /evidence="ECO:0000269|PubMed:7271787"
FT                   /id="PRO_0000020517"
FT   SITE            28
FT                   /note="Important for agonist activity on V1aR/AVPR1A"
FT                   /evidence="ECO:0000269|PubMed:18174156"
FT   MOD_RES         28
FT                   /note="Glycine amide"
FT                   /evidence="ECO:0000269|PubMed:13591312"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine"
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   VARIANT         17
FT                   /note="S -> F (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004980"
FT   VARIANT         19
FT                   /note="A -> T (in NDI; probably causes insufficient
FT                   processing of precursor; dbSNP:rs387906511)"
FT                   /evidence="ECO:0000269|PubMed:12519420,
FT                   ECO:0000269|PubMed:14673472, ECO:0000269|PubMed:8370682,
FT                   ECO:0000269|PubMed:8514868, ECO:0000269|PubMed:8554046,
FT                   ECO:0000269|PubMed:9580132"
FT                   /id="VAR_004981"
FT   VARIANT         19
FT                   /note="A -> V (in NDI; dbSNP:rs387906512)"
FT                   /evidence="ECO:0000269|PubMed:14673472,
FT                   ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004982"
FT   VARIANT         21
FT                   /note="Y -> H (in NDI; dbSNP:rs121964893)"
FT                   /evidence="ECO:0000269|PubMed:12107248"
FT                   /id="VAR_015262"
FT   VARIANT         26
FT                   /note="P -> L (in NDI; weakly active; dbSNP:rs142886338)"
FT                   /evidence="ECO:0000269|PubMed:10369876"
FT                   /id="VAR_015263"
FT   VARIANT         45
FT                   /note="G -> R (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004983"
FT   VARIANT         48
FT                   /note="G -> V (in NDI; dbSNP:rs121964883)"
FT                   /evidence="ECO:0000269|PubMed:1740104"
FT                   /id="VAR_004984"
FT   VARIANT         51
FT                   /note="R -> C (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004985"
FT   VARIANT         52
FT                   /note="C -> R (in NDI)"
FT                   /id="VAR_015264"
FT   VARIANT         54
FT                   /note="G -> R (in NDI; dbSNP:rs121964888)"
FT                   /evidence="ECO:0000269|PubMed:10487710,
FT                   ECO:0000269|PubMed:11980620, ECO:0000269|PubMed:14673472"
FT                   /id="VAR_015265"
FT   VARIANT         54
FT                   /note="G -> V (in NDI; dbSNP:rs121964887)"
FT                   /evidence="ECO:0000269|PubMed:9360520"
FT                   /id="VAR_015266"
FT   VARIANT         55
FT                   /note="P -> L (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8045958"
FT                   /id="VAR_004986"
FT   VARIANT         58
FT                   /note="C -> F (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:12931042"
FT                   /id="VAR_029997"
FT   VARIANT         59
FT                   /note="C -> R (in NDI)"
FT                   /id="VAR_015267"
FT   VARIANT         59
FT                   /note="C -> Y (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:11150885"
FT                   /id="VAR_015268"
FT   VARIANT         67
FT                   /note="V -> A (in NDI; dbSNP:rs28934878)"
FT                   /evidence="ECO:0000269|PubMed:14673472"
FT                   /id="VAR_019273"
FT   VARIANT         78
FT                   /note="E -> G (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472,
FT                   ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004988"
FT   VARIANT         78
FT                   /note="Missing (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472,
FT                   ECO:0000269|PubMed:8103767"
FT                   /id="VAR_004987"
FT   VARIANT         81
FT                   /note="L -> P (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004989"
FT   VARIANT         82
FT                   /note="P -> L (in dbSNP:rs5195)"
FT                   /id="VAR_011894"
FT   VARIANT         87
FT                   /note="S -> F (in NDI; dbSNP:rs121964890)"
FT                   /evidence="ECO:0000269|PubMed:9814475"
FT                   /id="VAR_015269"
FT   VARIANT         88
FT                   /note="G -> R (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004990"
FT   VARIANT         88
FT                   /note="G -> S (in NDI; dbSNP:rs121964882)"
FT                   /evidence="ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004991"
FT   VARIANT         92
FT                   /note="C -> S (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:12012274,
FT                   ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004992"
FT   VARIANT         92
FT                   /note="C -> Y (in NDI; dbSNP:rs121964891)"
FT                   /evidence="ECO:0000269|PubMed:11980620,
FT                   ECO:0000269|PubMed:9814475"
FT                   /id="VAR_015270"
FT   VARIANT         93
FT                   /note="G -> W (in NDI; dbSNP:rs121964885)"
FT                   /evidence="ECO:0000269|PubMed:7714110"
FT                   /id="VAR_004993"
FT   VARIANT         96
FT                   /note="G -> C (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472,
FT                   ECO:0000269|PubMed:8554046"
FT                   /id="VAR_004994"
FT   VARIANT         96
FT                   /note="G -> D (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472"
FT                   /id="VAR_019274"
FT   VARIANT         96
FT                   /note="G -> V (in NDI; dbSNP:rs121964886)"
FT                   /id="VAR_015271"
FT   VARIANT         97
FT                   /note="R -> C (in NDI)"
FT                   /id="VAR_015272"
FT   VARIANT         97
FT                   /note="R -> P (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:11748489"
FT                   /id="VAR_015273"
FT   VARIANT         98
FT                   /note="C -> G (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:11161827"
FT                   /id="VAR_015274"
FT   VARIANT         98
FT                   /note="C -> S (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:15538939"
FT                   /id="VAR_029998"
FT   VARIANT         99
FT                   /note="A -> P (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14510916"
FT                   /id="VAR_029999"
FT   VARIANT         104
FT                   /note="C -> F (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:12359138"
FT                   /id="VAR_015275"
FT   VARIANT         104
FT                   /note="C -> G (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472"
FT                   /id="VAR_019275"
FT   VARIANT         105
FT                   /note="C -> R (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:11980620"
FT                   /id="VAR_015276"
FT   VARIANT         105
FT                   /note="C -> Y (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:10677561"
FT                   /id="VAR_015279"
FT   VARIANT         116
FT                   /note="C -> G (in NDI; strong accumulation in the
FT                   endoplasmic reticulum and an altered morphology of this
FT                   organelle; dbSNP:rs74315383)"
FT                   /evidence="ECO:0000269|PubMed:11017955,
FT                   ECO:0000269|PubMed:11443218"
FT                   /id="VAR_015277"
FT   VARIANT         116
FT                   /note="C -> R (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:11017955"
FT                   /id="VAR_015278"
FT   VARIANT         116
FT                   /note="C -> W (in NDI)"
FT                   /evidence="ECO:0000269|PubMed:14673472"
FT                   /id="VAR_019276"
FT   VARIANT         119
FT                   /note="G -> V (in dbSNP:rs1051744)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_011895"
FT   MUTAGEN         28
FT                   /note="G->V: Gain of antagonist activity on V1aR/AVPR1A
FT                   (and loss of agonist activity on this receptor). 42-fold
FT                   decrease in affinity for V1aR/AVPR1A, 2000-fold decrease in
FT                   affinity for V1bR/AVPR1B, 5-fold decrease in affinity for
FT                   V2R/AVPR2 and no change in affinity for oxytocin receptor
FT                   (OXTR)."
FT                   /evidence="ECO:0000269|PubMed:18174156"
FT   CONFLICT        11
FT                   /note="L -> P (in Ref. 1; AAA98772)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        48
FT                   /note="G -> D (in Ref. 5; AAB86629)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   164 AA;  17325 MW;  8F5EF9834700B9AE CRC64;
     MPDTMLPACF LGLLAFSSAC YFQNCPRGGK RAMSDLELRQ CLPCGPGGKG RCFGPSICCA
     DELGCFVGTA EALRCQEENY LPSPCQSGQK ACGSGGRCAA FGVCCNDESC VTEPECREGF
     HRRARASDRS NATQLDGPAG ALLLRLVQLA GAPEPFEPAQ PDAY
//