ID   VIP_HUMAN               Reviewed;         170 AA.
AC   P01282; Q5TCY8; Q5TCY9; Q96QK3;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   13-FEB-2019, entry version 188.
DE   RecName: Full=VIP peptides;
DE   Contains:
DE     RecName: Full=Intestinal peptide PHV-42;
DE     AltName: Full=Peptide histidine valine 42;
DE   Contains:
DE     RecName: Full=Intestinal peptide PHM-27;
DE     AltName: Full=Peptide histidine methioninamide 27;
DE   Contains:
DE     RecName: Full=Vasoactive intestinal peptide;
DE              Short=VIP;
DE     AltName: Full=Vasoactive intestinal polypeptide;
DE   Flags: Precursor;
GN   Name=VIP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6571696; DOI=10.1038/304547a0;
RA   Itoh N., Obata K., Yanaihara N., Okamoto H.;
RT   "Human preprovasoactive intestinal polypeptide contains a novel PHI-
RT   27-like peptide, PHM-27.";
RL   Nature 304:547-549(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3899557;
RA   Tsukada T., Horovitch S.J., Montminy M.R., Mandel G., Goodman R.H.;
RT   "Structure of the human vasoactive intestinal polypeptide gene.";
RL   DNA 4:293-300(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=2995945; DOI=10.1016/0196-9781(85)90016-6;
RA   Delamarter J.F., Buell G.N., Kawashima E., Polak J.M., Bloom S.R.;
RT   "Vasoactive intestinal peptide: expression of the prohormone in
RT   bacterial cells.";
RL   Peptides 6 Suppl. 1:95-102(1985).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3025882; DOI=10.1073/pnas.84.2.605;
RA   Linder S., Barkhem T., Norberg A., Persson H., Schalling M.,
RA   Hoekfelt T., Magnusson G.;
RT   "Structure and expression of the gene encoding the vasoactive
RT   intestinal peptide precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:605-609(1987).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2839091; DOI=10.1111/j.1749-6632.1988.tb26975.x;
RA   Yamagami T., Ohsawa K., Nishizawa M., Inoue C., Gotoh E.,
RA   Yanaihara N., Yamamoto H., Okamoto H.;
RT   "Complete nucleotide sequence of human vasoactive intestinal
RT   peptide/PHM-27 gene and its inducible promoter.";
RL   Ann. N. Y. Acad. Sci. 527:87-102(1988).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA   Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA   Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA   Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA   Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA   Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA   Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA   Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA   Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA   Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA   Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA   Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA   McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA   Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA   Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA   Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA   Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA   Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA   Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA   Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA   Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA   Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Prostate;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-170, AND AMIDATION AT MET-107
RP   AND ASN-152.
RX   PubMed=3748844; DOI=10.1016/0196-9781(86)90156-7;
RA   Gozes I., Bodener M., Shani Y., Fridkin M.;
RT   "Structure and expression of the vasoactive intestinal peptide (VIP)
RT   gene in a human tumor.";
RL   Peptides 7:1-6(1986).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 50-170 (ISOFORM 1).
RC   TISSUE=Pancreatic carcinoma;
RX   PubMed=6139527; DOI=10.1016/S0140-6736(83)91215-1;
RA   Bloom S.R., Delamarter J.F., Kawashima E., Christofides N.D.,
RA   Buell G., Polak J.M.;
RT   "Diarrhoea in vipoma patients associated with cosecretion of a second
RT   active peptide (peptide histidine isoleucine) explained by single
RT   coding gene.";
RL   Lancet 2:1163-1165(1983).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 78-155.
RX   PubMed=2434617; DOI=10.1111/j.1471-4159.1987.tb05638.x;
RA   Gozes I., Giladi E., Shani Y.;
RT   "Vasoactive intestinal peptide gene: putative mechanism of information
RT   storage at the RNA level.";
RL   J. Neurochem. 48:1136-1141(1987).
RN   [11]
RP   PROTEIN SEQUENCE OF 81-122.
RX   PubMed=3654650;
RA   Yiangou Y., di Marzo V., Spokes R.A., Panico M., Morris H.R.,
RA   Bloom S.R.;
RT   "Isolation, characterization, and pharmacological actions of peptide
RT   histidine valine 42, a novel prepro-vasoactive intestinal peptide-
RT   derived peptide.";
RL   J. Biol. Chem. 262:14010-14013(1987).
RN   [12]
RP   PROTEIN SEQUENCE OF 127-152.
RC   TISSUE=Pheochromocytoma;
RX   PubMed=1318039; DOI=10.1016/S0006-291X(05)80966-0;
RA   Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Matsuo H., Eto T.;
RT   "Isolation and characterization of peptides which act on rat
RT   platelets, from a pheochromocytoma.";
RL   Biochem. Biophys. Res. Commun. 185:134-141(1992).
RN   [13]
RP   FUNCTION (PHM-27).
RX   PubMed=15013843; DOI=10.1016/j.bcp.2003.11.008;
RA   Ma J.N., Currier E.A., Essex A., Feddock M., Spalding T.A., Nash N.R.,
RA   Brann M.R., Burstein E.S.;
RT   "Discovery of novel peptide/receptor interactions: identification of
RT   PHM-27 as a potent agonist of the human calcitonin receptor.";
RL   Biochem. Pharmacol. 67:1279-1284(2004).
RN   [14]
RP   STRUCTURE BY NMR OF VIP.
RX   PubMed=1863695; DOI=10.1002/bip.360310411;
RA   Theriault Y., Boulanger Y., St Pierre S.;
RT   "Structural determination of the vasoactive intestinal peptide by two-
RT   dimensional H-NMR spectroscopy.";
RL   Biopolymers 31:459-464(1991).
CC   -!- FUNCTION: VIP causes vasodilation, lowers arterial blood pressure,
CC       stimulates myocardial contractility, increases glycogenolysis and
CC       relaxes the smooth muscle of trachea, stomach and gall bladder.
CC       {ECO:0000269|PubMed:15013843}.
CC   -!- FUNCTION: PHM and PHV also cause vasodilation. PHM-27 is a potent
CC       agonist of the calcitonin receptor CALCR, with similar efficacy as
CC       calcitonin. {ECO:0000269|PubMed:15013843}.
CC   -!- INTERACTION:
CC       P27487:DPP4; NbExp=2; IntAct=EBI-751454, EBI-2871277;
CC       Q12884:FAP; NbExp=2; IntAct=EBI-751454, EBI-4319803;
CC       O43765:SGTA; NbExp=3; IntAct=EBI-751454, EBI-347996;
CC       P32241:VIPR1; NbExp=2; IntAct=EBI-6656819, EBI-3917984;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P01282-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P01282-2; Sequence=VSP_023256;
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Vasoactive intestinal peptide
CC       entry;
CC       URL="https://en.wikipedia.org/wiki/Vasoactive_intestinal_peptide";
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DR   EMBL; L00157; AAA61289.1; -; Genomic_DNA.
DR   EMBL; L00154; AAA61289.1; JOINED; Genomic_DNA.
DR   EMBL; L00155; AAA61289.1; JOINED; Genomic_DNA.
DR   EMBL; L00156; AAA61289.1; JOINED; Genomic_DNA.
DR   EMBL; M11553; AAA61284.1; -; Genomic_DNA.
DR   EMBL; M11549; AAA61284.1; JOINED; Genomic_DNA.
DR   EMBL; M11550; AAA61284.1; JOINED; Genomic_DNA.
DR   EMBL; M11551; AAA61284.1; JOINED; Genomic_DNA.
DR   EMBL; M11552; AAA61284.1; JOINED; Genomic_DNA.
DR   EMBL; M36634; AAA61287.1; -; mRNA.
DR   EMBL; M14623; AAA61288.1; -; Genomic_DNA.
DR   EMBL; M14619; AAA61288.1; JOINED; Genomic_DNA.
DR   EMBL; M14620; AAA61288.1; JOINED; Genomic_DNA.
DR   EMBL; M14621; AAA61288.1; JOINED; Genomic_DNA.
DR   EMBL; M14622; AAA61288.1; JOINED; Genomic_DNA.
DR   EMBL; M33027; AAA69515.1; -; Genomic_DNA.
DR   EMBL; AL133356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC009794; AAH09794.1; -; mRNA.
DR   EMBL; M36610; AAA61286.1; -; Genomic_DNA.
DR   EMBL; M36606; AAA61286.1; JOINED; Genomic_DNA.
DR   EMBL; M36607; AAA61286.1; JOINED; Genomic_DNA.
DR   EMBL; M36608; AAA61286.1; JOINED; Genomic_DNA.
DR   EMBL; M36609; AAA61286.1; JOINED; Genomic_DNA.
DR   EMBL; M54930; AAA63268.1; -; mRNA.
DR   EMBL; M32162; AAA61285.1; -; Genomic_DNA.
DR   EMBL; M31645; AAA61285.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS5240.1; -. [P01282-1]
DR   CCDS; CCDS5241.1; -. [P01282-2]
DR   PIR; A23296; VRHU.
DR   RefSeq; NP_003372.1; NM_003381.3. [P01282-1]
DR   RefSeq; NP_919416.1; NM_194435.2. [P01282-2]
DR   UniGene; Hs.53973; -.
DR   PDB; 2RRH; NMR; -; A=125-153.
DR   PDB; 2RRI; NMR; -; A=125-153.
DR   PDBsum; 2RRH; -.
DR   PDBsum; 2RRI; -.
DR   ProteinModelPortal; P01282; -.
DR   SMR; P01282; -.
DR   BioGrid; 113273; 9.
DR   IntAct; P01282; 9.
DR   MINT; P01282; -.
DR   STRING; 9606.ENSP00000356213; -.
DR   ChEMBL; CHEMBL5737; -.
DR   iPTMnet; P01282; -.
DR   PhosphoSitePlus; P01282; -.
DR   BioMuta; VIP; -.
DR   DMDM; 138574; -.
DR   jPOST; P01282; -.
DR   PaxDb; P01282; -.
DR   PeptideAtlas; P01282; -.
DR   PRIDE; P01282; -.
DR   ProteomicsDB; 51368; -.
DR   ProteomicsDB; 51369; -. [P01282-2]
DR   DNASU; 7432; -.
DR   Ensembl; ENST00000367243; ENSP00000356212; ENSG00000146469. [P01282-2]
DR   Ensembl; ENST00000367244; ENSP00000356213; ENSG00000146469. [P01282-1]
DR   GeneID; 7432; -.
DR   KEGG; hsa:7432; -.
DR   UCSC; uc003qpe.6; human. [P01282-1]
DR   CTD; 7432; -.
DR   DisGeNET; 7432; -.
DR   EuPathDB; HostDB:ENSG00000146469.12; -.
DR   GeneCards; VIP; -.
DR   HGNC; HGNC:12693; VIP.
DR   HPA; CAB018649; -.
DR   HPA; HPA017324; -.
DR   HPA; HPA072701; -.
DR   MIM; 192320; gene.
DR   neXtProt; NX_P01282; -.
DR   OpenTargets; ENSG00000146469; -.
DR   PharmGKB; PA37312; -.
DR   eggNOG; ENOG410IW68; Eukaryota.
DR   eggNOG; ENOG4111JKK; LUCA.
DR   GeneTree; ENSGT00940000158495; -.
DR   HOGENOM; HOG000253943; -.
DR   HOVERGEN; HBG018069; -.
DR   InParanoid; P01282; -.
DR   KO; K05264; -.
DR   OMA; FSHTLAW; -.
DR   OrthoDB; 1343108at2759; -.
DR   PhylomeDB; P01282; -.
DR   TreeFam; TF332804; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   SIGNOR; P01282; -.
DR   EvolutionaryTrace; P01282; -.
DR   GeneWiki; Vasoactive_intestinal_peptide; -.
DR   GenomeRNAi; 7432; -.
DR   PRO; PR:P01282; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   Bgee; ENSG00000146469; Expressed in 127 organ(s), highest expression level in fundus of stomach.
DR   ExpressionAtlas; P01282; baseline and differential.
DR   Genevisible; P01282; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0043204; C:perikaryon; IBA:GO_Central.
DR   GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR   GO; GO:0051428; F:peptide hormone receptor binding; IPI:GO_Central.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR   GO; GO:0019732; P:antifungal humoral response; IDA:UniProtKB.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR   GO; GO:0007589; P:body fluid secretion; TAS:ProtInc.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR   GO; GO:0048242; P:epinephrine secretion; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR   GO; GO:0007611; P:learning or memory; IBA:GO_Central.
DR   GO; GO:0048255; P:mRNA stabilization; ISS:AgBase.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:0043267; P:negative regulation of potassium ion transport; IBA:GO_Central.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IBA:GO_Central.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0097755; P:positive regulation of blood vessel diameter; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IBA:GO_Central.
DR   GO; GO:0032812; P:positive regulation of epinephrine secretion; IBA:GO_Central.
DR   GO; GO:0060406; P:positive regulation of penile erection; IBA:GO_Central.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:BHF-UCL.
DR   GO; GO:0070459; P:prolactin secretion; ISS:AgBase.
DR   GO; GO:0032880; P:regulation of protein localization; IDA:BHF-UCL.
DR   GO; GO:0051930; P:regulation of sensory perception of pain; IBA:GO_Central.
DR   GO; GO:0001878; P:response to yeast; IDA:UniProtKB.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   InterPro; IPR015523; VIP.
DR   PANTHER; PTHR11213:SF5; PTHR11213:SF5; 1.
DR   Pfam; PF00123; Hormone_2; 2.
DR   SMART; SM00070; GLUCA; 2.
DR   PROSITE; PS00260; GLUCAGON; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Hormone; Phosphoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   PROPEP       21     79
FT                                /FTId=PRO_0000011457.
FT   PEPTIDE      81    122       Intestinal peptide PHV-42.
FT                                /FTId=PRO_0000011458.
FT   PEPTIDE      81    107       Intestinal peptide PHM-27.
FT                                /FTId=PRO_0000011459.
FT   PEPTIDE     125    152       Vasoactive intestinal peptide.
FT                                /FTId=PRO_0000011460.
FT   PROPEP      156    170
FT                                /FTId=PRO_0000011461.
FT   MOD_RES      76     76       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P01283}.
FT   MOD_RES     107    107       Methionine amide.
FT                                {ECO:0000269|PubMed:3748844}.
FT   MOD_RES     152    152       Asparagine amide.
FT                                {ECO:0000269|PubMed:3748844}.
FT   VAR_SEQ     113    113       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_023256.
FT   CONFLICT     96     97       QL -> PP (in Ref. 8; AAA61286).
FT                                {ECO:0000305}.
FT   CONFLICT    116    116       S -> L (in Ref. 4; AAA61288).
FT                                {ECO:0000305}.
FT   CONFLICT    136    136       R -> G (in Ref. 4; AAA61288).
FT                                {ECO:0000305}.
FT   HELIX       128    152       {ECO:0000244|PDB:2RRH}.
SQ   SEQUENCE   170 AA;  19169 MW;  93EC0177F89508FD CRC64;
     MDTRNKAQLL VLLTLLSVLF SQTSAWPLYR APSALRLGDR IPFEGANEPD QVSLKEDIDM
     LQNALAENDT PYYDVSRNAR HADGVFTSDF SKLLGQLSAK KYLESLMGKR VSSNISEDPV
     PVKRHSDAVF TDNYTRLRKQ MAVKKYLNSI LNGKRSSEGE SPDFPEELEK
//