Reviewed, UniProtKB/Swiss-Prot P01185 (NEU2_HUMAN)

Names and origin

Protein names

Recommended name:
    Vasopressin-neurophysin 2-copeptin
Alternative name(s):
    AVP-NPII
Cleaved into the following 3 chains:
    1- Recommended name:
            Arg-vasopressin
    2- Recommended name:
            Neurophysin 2
        Alternative name(s):
            Neurophysin-II
    3- Recommended name:
            Copeptin

Gene names

Name:	AVP
Synonyms:	ARVP, VP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	164 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Neurophysin 2 specifically binds vasopressin. Vasopressin has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels.
Subcellular location	Secreted.
Involvement in disease	Defects in AVP are the cause of autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) [MIM:125700]. ADNDI is characterized by persistent thirst, polydipsia and polyuria. The disease is transmitted in an autosomal dominant mode and appears to be largely if not completely penetrant. Defects in AVP are the cause of autosomal recessive neurohypophyseal diabetes insipidus (ARNDI) [MIM:125700]. ARNDI is characterized by persistent thirst, polydipsia and polyuria. Most mutations are hypothesized to trigger neurodegeneration via disruption of preproAVP-NPII processing.
Sequence similarities	Belongs to the vasopressin/oxytocin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Diabetes insipidus Disease mutation
Domain	Signal
Molecular function	Hormone Vasoactive Vasoconstrictor
PTM	Amidation Cleavage on pair of basic residues Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.4 Traceable author statement. Source: ProtInc generation of precursor metabolites and energy Ref.4 Traceable author statement. Source: ProtInc signal transduction Traceable author statement. Source: ProtInc vasoconstriction Inferred from electronic annotation. Source: UniProtKB-KW water transport Ref.4 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: InterPro soluble fraction Ref.4 Traceable author statement. Source: ProtInc
Molecular function	neurohypophyseal hormone activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Peptide	20 – 28	9	Arg-vasopressin		PRO_0000020515
	Chain	32 – 124	93	Neurophysin 2		PRO_0000020516
	Peptide	126 – 164	39	Copeptin		PRO_0000020517
Amino acid modifications
	Modified residue	28	1	Glycine amide
	Glycosylation	131	1	N-linked (GlcNAc...)
	Disulfide bond	20 ↔ 25
	Disulfide bond	41 ↔ 85		By similarity
	Disulfide bond	44 ↔ 58		By similarity
	Disulfide bond	52 ↔ 75		By similarity
	Disulfide bond	59 ↔ 65		By similarity
	Disulfide bond	92 ↔ 104		By similarity
	Disulfide bond	98 ↔ 116		By similarity
	Disulfide bond	105 ↔ 110		By similarity
Natural variations
	Natural variant	17	1	S → F in ADNDI.		VAR_004980
	Natural variant	19	1	A → T in ADNDI; probably causes insufficient processing of precursor.		VAR_004981
	Natural variant	19	1	A → V in ADNDI.		VAR_004982
	Natural variant	21	1	Y → H in ADNDI.		VAR_015262
	Natural variant	26	1	P → L in ARNDI; weakly active.		VAR_015263
	Natural variant	45	1	G → R in ADNDI.		VAR_004983
	Natural variant	48	1	G → V in ADNDI.		VAR_004984
	Natural variant	51	1	R → C in ADNDI.		VAR_004985
	Natural variant	52	1	C → R in ADNDI.		VAR_015264
	Natural variant	54	1	G → R in ADNDI.		VAR_015265
	Natural variant	54	1	G → V in ADNDI.		VAR_015266
	Natural variant	55	1	P → L in ADNDI.		VAR_004986
	Natural variant	58	1	C → F in ADNDI.		VAR_029997
	Natural variant	59	1	C → R in ADNDI.		VAR_015267
	Natural variant	59	1	C → Y in ADNDI.		VAR_015268
	Natural variant	67	1	V → A in ADNDI.		VAR_019273
	Natural variant	78	1	E → G in ADNDI.		VAR_004988
	Natural variant	78	1	Missing in ADNDI.		VAR_004987
	Natural variant	81	1	L → P in ADNDI.		VAR_004989
	Natural variant	82	1	P → L: dbSNP rs5195.		VAR_011894
	Natural variant	87	1	S → F in ADNDI.		VAR_015269
	Natural variant	88	1	G → R in ADNDI.		VAR_004990
	Natural variant	88	1	G → S in ADNDI.		VAR_004991
	Natural variant	92	1	C → S in ADNDI.		VAR_004992
	Natural variant	92	1	C → Y in ADNDI.		VAR_015270
	Natural variant	93	1	G → W in ADNDI.		VAR_004993
	Natural variant	96	1	G → C in ADNDI.		VAR_004994
	Natural variant	96	1	G → D in ADNDI.		VAR_019274
	Natural variant	96	1	G → V in ADNDI.		VAR_015271
	Natural variant	97	1	R → C in ADNDI.		VAR_015272
	Natural variant	97	1	R → P in ADNDI.		VAR_015273
	Natural variant	98	1	C → G in ADNDI.		VAR_015274
	Natural variant	98	1	C → S in ADNDI.		VAR_029998
	Natural variant	99	1	A → P in ADNDI.		VAR_029999
	Natural variant	104	1	C → F in ADNDI.		VAR_015275
	Natural variant	104	1	C → G in ADNDI.		VAR_019275
	Natural variant	105	1	C → R in ADNDI.		VAR_015276
	Natural variant	105	1	C → Y in ADNDI.		VAR_015279
	Natural variant	116	1	C → G in ADNDI; strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle.		VAR_015277
	Natural variant	116	1	C → R in ADNDI.		VAR_015278
	Natural variant	116	1	C → W in ADNDI.		VAR_019276
	Natural variant	119	1	G → V: dbSNP rs1051744.		VAR_011895
Experimental info
	Sequence conflict	11	1	L → P in AAA98772. Ref.1
	Sequence conflict	48	1	G → D in AAB86629. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P01185-1 [UniParc]. Last modified August 1, 1992. Version 2. Checksum: 8F5EF9834700B9AE	FASTA	164	17,325
	10 20 30 40 50 60 MPDTMLPACF LGLLAFSSAC YFQNCPRGGK RAMSDLELRQ CLPCGPGGKG RCFGPSICCA 70 80 90 100 110 120 DELGCFVGTA EALRCQEENY LPSPCQSGQK ACGSGGRCAA FGVCCNDESC VTEPECREGF 130 140 150 160 HRRARASDRS NATQLDGPAG ALLLRLVQLA GAPEPFEPAQ PDAY

References

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[1]	"The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line." Sausville E., Carney D., Battey J. J. Biol. Chem. 260:10236-10241(1985) [PubMed: 2991279] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The neurohypophyseal hormones vasopressin and oxytocin. Precursor structure, synthesis and regulation." Rehbein M., Hillers M., Mohr E., Ivell R., Morley S., Schmale H., Richter D. Biol. Chem. Hoppe-Seyler 367:695-704(1986) [PubMed: 3768139] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Expression of the vasopressin and oxytocin genes in human hypothalami." Mohr E., Hillers M., Ivell R., Haulica I.D., Richter D. FEBS Lett. 193:12-16(1985) [PubMed: 4065330] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus." Bahnsen U., Oosting P., Swaab D.F., Nahke P., Richter D., Schmale H. EMBO J. 11:19-23(1992) [PubMed: 1740104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ADNDI VAL-48.
[5]	"A missense mutation in the vasopressin mRNA with human small-cell lung carcinoma." Du J., North W.G. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-119. Tissue: Lung carcinoma.
[6]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"On the nature of oxytocin and vasopressin from human pituitary." Light A., du Vigneaud V. Proc. Soc. Exp. Biol. Med. 98:692-696(1958) [PubMed: 13591312] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-28.
[9]	"Identification of human neurophysins: complete amino acid sequences of MSEL- and VLDV-neurophysins." Chauvet M.-T., Hurpet D., Chauvet J., Acher R. Proc. Natl. Acad. Sci. U.S.A. 80:2839-2843(1983) [PubMed: 6574452] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-124.
[10]	"The complete sequence of a novel human pituitary glycopeptide homologous to pig posterior pituitary glycopeptide." Seidah N.G., Benjannet S., Chretien M. Biochem. Biophys. Res. Commun. 100:901-907(1981) [PubMed: 7271787] [Abstract] Cited for: PROTEIN SEQUENCE OF 126-164.
[11]	"Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation." McLeod J.F., Kovacs L., Gaskill M.B., Rittig S., Bradley G.S., Robertson G.L. J. Clin. Endocrinol. Metab. 77:599A-599G(1993) [PubMed: 8370682] [Abstract] Cited for: VARIANT ADNDI THR-19.
[12]	"Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus." Yuasa H., Ito M., Nagasaki H., Oiso Y., Miyamoto S., Sasaki N., Saito H. J. Clin. Endocrinol. Metab. 77:600-604(1993) [PubMed: 8103767] [Abstract] Cited for: VARIANT ADNDI GLU-78 DEL.
[13]	"Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus." Ito M., Oiso Y., Murase T., Kondo K., Saito H., Chinzei T., Racchi M., Lively M.O. J. Clin. Invest. 91:2565-2571(1993) [PubMed: 8514868] [Abstract] Cited for: VARIANT ADNDI THR-19.
[14]	"A de novo mutation in the coding sequence for neurophysin-II (Pro24-->Leu) is associated with onset and transmission of autosomal dominant neurohypophyseal diabetes insipidus." Repaske D.R., Browning J.E. J. Clin. Endocrinol. Metab. 79:421-427(1994) [PubMed: 8045958] [Abstract] Cited for: VARIANT ADNDI LEU-55.
[15]	"Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus." Nagasaki H., Ito M., Yuasa H., Saito H., Fukase M., Hamada K., Ishikawa E., Katakami H., Oiso Y. J. Clin. Endocrinol. Metab. 80:1352-1356(1995) [PubMed: 7714110] [Abstract] Cited for: VARIANT ADNDI TRP-93.
[16]	"Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus." Rittig S., Robertson G.L., Siggaard C., Kovacs L., Gregersen N., Nyborg J., Pedersen E.B. Am. J. Hum. Genet. 58:107-117(1996) [PubMed: 8554046] [Abstract] Cited for: VARIANTS ADNDI PHE-17; THR-19; VAL-19; ARG-45; CYS-51; GLY-78; PRO-81; ARG-88; SER-88; SER-92 AND CYS-96.
[17]	"Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23-->Val in neurophysin II." Gagliardi P.C., Bernasconi S., Repaske D.R. J. Clin. Endocrinol. Metab. 82:3643-3646(1997) [PubMed: 9360520] [Abstract] Cited for: VARIANT ADNDI VAL-54.
[18]	"Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus." Calvo B., Bilbao J.R., Urrutia I., Eizaguirre J., Gaztambide S., Castano L. J. Clin. Endocrinol. Metab. 83:995-997(1998) [PubMed: 9580132] [Abstract] Cited for: VARIANT ADNDI THR-19.
[19]	"Two novel mutations of the vasopressin gene associated with familial diabetes insipidus and identification of an asymptomatic carrier infant." Grant F.D., Ahmadi A., Hosley C.M., Majzoub J.A. J. Clin. Endocrinol. Metab. 83:3958-3964(1998) [PubMed: 9814475] [Abstract] Cited for: VARIANTS ADNDI PHE-87 AND TYR-92.
[20]	"Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin." Willcutts M.D., Felner E., White P.C. Hum. Mol. Genet. 8:1303-1307(1999) [PubMed: 10369876] [Abstract] Cit