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   24-JAN-2024, entry version 215.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   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-27-like
RT   peptide, PHM-27.";
RL   Nature 304:547-549(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3899557; DOI=10.1089/dna.1985.4.293;
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 bacterial
RT   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., Hoekfelt T.,
RA   Magnusson G.;
RT   "Structure and expression of the gene encoding the vasoactive intestinal
RT   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., Yanaihara N.,
RA   Yamamoto H., Okamoto H.;
RT   "Complete nucleotide sequence of human vasoactive intestinal peptide/PHM-27
RT   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., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., 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., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   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 project:
RT   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 AND
RP   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) gene
RT   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., Buell G.,
RA   Polak J.M.;
RT   "Diarrhoea in vipoma patients associated with cosecretion of a second
RT   active peptide (peptide histidine isoleucine) explained by single coding
RT   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; DOI=10.1016/s0021-9258(18)47896-9;
RA   Yiangou Y., di Marzo V., Spokes R.A., Panico M., Morris H.R., Bloom S.R.;
RT   "Isolation, characterization, and pharmacological actions of peptide
RT   histidine valine 42, a novel prepro-vasoactive intestinal peptide-derived
RT   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 platelets,
RT   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 PHM-27
RT   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       P01282; P27487: DPP4; NbExp=2; IntAct=EBI-751454, EBI-2871277;
CC       P01282; Q12884: FAP; NbExp=2; IntAct=EBI-751454, EBI-4319803;
CC       P01282; O43765: SGTA; NbExp=3; IntAct=EBI-751454, EBI-347996;
CC       P01282-2; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-12320391, EBI-11962928;
CC       P01282-2; P10620: MGST1; NbExp=3; IntAct=EBI-12320391, EBI-2691601;
CC       P01282-2; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12320391, EBI-947187;
CC       PRO_0000011460; 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 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   PDB; 2RRH; NMR; -; A=125-153.
DR   PDB; 2RRI; NMR; -; A=125-153.
DR   PDB; 8E3Z; EM; 2.70 A; P=125-152.
DR   PDBsum; 2RRH; -.
DR   PDBsum; 2RRI; -.
DR   PDBsum; 8E3Z; -.
DR   AlphaFoldDB; P01282; -.
DR   BMRB; P01282; -.
DR   SMR; P01282; -.
DR   BioGRID; 113273; 19.
DR   IntAct; P01282; 14.
DR   MINT; P01282; -.
DR   STRING; 9606.ENSP00000356213; -.
DR   BindingDB; P01282; -.
DR   ChEMBL; CHEMBL5737; -.
DR   iPTMnet; P01282; -.
DR   PhosphoSitePlus; P01282; -.
DR   BioMuta; VIP; -.
DR   DMDM; 138574; -.
DR   MassIVE; P01282; -.
DR   PaxDb; 9606-ENSP00000356213; -.
DR   PeptideAtlas; P01282; -.
DR   ProteomicsDB; 51368; -. [P01282-1]
DR   ProteomicsDB; 51369; -. [P01282-2]
DR   ABCD; P01282; 2 sequenced antibodies.
DR   Antibodypedia; 3435; 619 antibodies from 41 providers.
DR   DNASU; 7432; -.
DR   Ensembl; ENST00000367243.7; ENSP00000356212.3; ENSG00000146469.13. [P01282-2]
DR   Ensembl; ENST00000367244.8; ENSP00000356213.3; ENSG00000146469.13. [P01282-1]
DR   GeneID; 7432; -.
DR   KEGG; hsa:7432; -.
DR   MANE-Select; ENST00000367244.8; ENSP00000356213.3; NM_003381.4; NP_003372.1.
DR   UCSC; uc003qpe.6; human. [P01282-1]
DR   AGR; HGNC:12693; -.
DR   CTD; 7432; -.
DR   DisGeNET; 7432; -.
DR   GeneCards; VIP; -.
DR   HGNC; HGNC:12693; VIP.
DR   HPA; ENSG00000146469; Tissue enhanced (intestine, lymphoid tissue).
DR   MIM; 192320; gene.
DR   neXtProt; NX_P01282; -.
DR   OpenTargets; ENSG00000146469; -.
DR   PharmGKB; PA37312; -.
DR   VEuPathDB; HostDB:ENSG00000146469; -.
DR   eggNOG; ENOG502QVTA; Eukaryota.
DR   GeneTree; ENSGT00950000183154; -.
DR   HOGENOM; CLU_133877_1_0_1; -.
DR   InParanoid; P01282; -.
DR   OMA; MEVRSKP; -.
DR   OrthoDB; 4164373at2759; -.
DR   PhylomeDB; P01282; -.
DR   TreeFam; TF332804; -.
DR   PathwayCommons; P01282; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   SignaLink; P01282; -.
DR   SIGNOR; P01282; -.
DR   BioGRID-ORCS; 7432; 13 hits in 1145 CRISPR screens.
DR   EvolutionaryTrace; P01282; -.
DR   GeneWiki; Vasoactive_intestinal_peptide; -.
DR   GenomeRNAi; 7432; -.
DR   Pharos; P01282; Tbio.
DR   PRO; PR:P01282; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P01282; Protein.
DR   Bgee; ENSG00000146469; Expressed in vermiform appendix and 115 other cell types or tissues.
DR   ExpressionAtlas; P01282; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0043005; C:neuron projection; 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:0007589; P:body fluid secretion; TAS:ProtInc.
DR   GO; GO:0048242; P:epinephrine secretion; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
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: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   Gene3D; 6.10.250.590; -; 2.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   InterPro; IPR046963; VIP/GHRH-like.
DR   PANTHER; PTHR11213; GLUCAGON-FAMILY NEUROPEPTIDE; 1.
DR   PANTHER; PTHR11213:SF5; VIP PEPTIDES; 1.
DR   Pfam; PF00123; Hormone_2; 2.
DR   SMART; SM00070; GLUCA; 2.
DR   PROSITE; PS00260; GLUCAGON; 2.
DR   Genevisible; P01282; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Direct protein sequencing; Hormone;
KW   Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..79
FT                   /id="PRO_0000011457"
FT   PEPTIDE         81..122
FT                   /note="Intestinal peptide PHV-42"
FT                   /id="PRO_0000011458"
FT   PEPTIDE         81..107
FT                   /note="Intestinal peptide PHM-27"
FT                   /id="PRO_0000011459"
FT   PEPTIDE         125..152
FT                   /note="Vasoactive intestinal peptide"
FT                   /id="PRO_0000011460"
FT   PROPEP          156..170
FT                   /id="PRO_0000011461"
FT   MOD_RES         76
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P01283"
FT   MOD_RES         107
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000269|PubMed:3748844"
FT   MOD_RES         152
FT                   /note="Asparagine amide"
FT                   /evidence="ECO:0000269|PubMed:3748844"
FT   VAR_SEQ         113
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_023256"
FT   CONFLICT        96..97
FT                   /note="QL -> PP (in Ref. 8; AAA61286)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116
FT                   /note="S -> L (in Ref. 4; AAA61288)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        136
FT                   /note="R -> G (in Ref. 4; AAA61288)"
FT                   /evidence="ECO:0000305"
FT   HELIX           128..152
FT                   /evidence="ECO:0007829|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
//