P41587 (VIPR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vasoactive intestinal polypeptide receptor 2
Short name=VIP-R-2

Alternative name(s):
Helodermin-preferring VIP receptor
Pituitary adenylate cyclase-activating polypeptide type III receptor
Short name=PACAP type III receptor
Short name=PACAP-R-3
Short name=PACAP-R3
VPAC2

Gene names

Name:	VIPR2
Synonyms:	VIP2R

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	438 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	This is a receptor for VIP as well as PACAP-38 and -27, the activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Can be coupled to phospholipase C. Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in CD4+ T-cells, but not in CD8+ T-cells. Expressed in the T-cell lines Jurkat, Peer, MOLT-4, HSB, YT and SUP-T1, but not in the T-cell lines HARRIS and HuT 78. Ref.9
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement PubMed 8757618. Source: ProtInc negative regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.1. Source: ProtInc vasoactive intestinal polypeptide receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Chain

24 – 438

415

Vasoactive intestinal polypeptide receptor 2

PRO_0000012860

Regions

Topological domain

24 – 126

103

Extracellular Potential

Transmembrane

127 – 151

25

Helical; Name=1; Potential

Topological domain

152 – 158

7

Cytoplasmic Potential

Transmembrane

159 – 178

20

Helical; Name=2; Potential

Topological domain

179 – 203

25

Extracellular Potential

Transmembrane

204 – 227

24

Helical; Name=3; Potential

Topological domain

228 – 240

13

Cytoplasmic Potential

Transmembrane

241 – 262

22

Helical; Name=4; Potential

Topological domain

263 – 279

17

Extracellular Potential

Transmembrane

280 – 303

24

Helical; Name=5; Potential

Topological domain

304 – 328

25

Cytoplasmic Potential

Transmembrane

329 – 348

20

Helical; Name=6; Potential

Topological domain

349 – 360

12

Extracellular Potential

Transmembrane

361 – 380

20

Helical; Name=7; Potential

Topological domain

381 – 438

58

Cytoplasmic Potential

Amino acid modifications

Modified residue

415

1

Phosphoserine By similarity

Glycosylation

58

1

N-linked (GlcNAc...) Potential

Glycosylation

88

1

N-linked (GlcNAc...) Potential

Glycosylation

92

1

N-linked (GlcNAc...) Potential

Disulfide bond

38 ↔ 61

Ref.10

Disulfide bond

52 ↔ 93

Ref.10

Disulfide bond

75 ↔ 109

Ref.10

Disulfide bond

202 ↔ 271

By similarity

Natural variations

Natural variant

39

1

A → T.
Corresponds to variant rs1062609 [ dbSNP | Ensembl ].

VAR_011811

Natural variant

412

1

R → H.
Corresponds to variant rs1042620 [ dbSNP | Ensembl ].

VAR_011812

Experimental info

Sequence conflict

424

1

G → A in AAC37569. Ref.1

Sequence conflict

424

1

G → A in AAC41756. Ref.1

Sequence conflict

424

1

G → A in AAC50872. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

438

Helix Strand Turn

Details...

Helix

26 – 44

19

Turn

45 – 47

3

Beta strand

55 – 57

3

Beta strand

60 – 62

3

Beta strand

70 – 74

5

Helix

77 – 82

6

Beta strand

83 – 85

3

Beta strand

88 – 94

7

Helix

105 – 109

5

Sequences

	Sequence		Length	Mass (Da)
	P41587 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 265A43A70BE09699	FASTA	438	49,479
	10 20 30 40 50 60 MRTLLPPALL TCWLLAPVNS IHPECRFHLE IQEEETKCAE LLRSQTEKHK ACSGVWDNIT 70 80 90 100 110 120 CWRPANVGET VTVPCPKVFS NFYSKAGNIS KNCTSDGWSE TFPDFVDACG YSDPEDESKI 130 140 150 160 170 180 TFYILVKAIY TLGYSVSLMS LATGSIILCL FRKLHCTRNY IHLNLFLSFI LRAISVLVKD 190 200 210 220 230 240 DVLYSSSGTL HCPDQPSSWV GCKLSLVFLQ YCIMANFFWL LVEGLYLHTL LVAMLPPRRC 250 260 270 280 290 300 FLAYLLIGWG LPTVCIGAWT AARLYLEDTG CWDTNDHSVP WWVIRIPILI SIIVNFVLFI 310 320 330 340 350 360 SIIRILLQKL TSPDVGGNDQ SQYKRLAKST LLLIPLFGVH YMVFAVFPIS ISSKYQILFE 370 380 390 400 410 420 LCLGSFQGLV VAVLYCFLNS EVQCELKRKW RSRCPTPSAS RDYRVCGSSF SRNGSEGALQ 430 FHRGSRAQSF LQTETSVI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional characterization of a human VIP receptor from SUP-T1 lymphoblasts." Svoboda M., Tastenoy M., van Rampelbergh J., Goossens J.-F., Neef P., Waelbroeck M., Robberecht P. Biochem. Biophys. Res. Commun. 205:1617-1624(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Chromosomal localization in mouse and human of the vasoactive intestinal peptide receptor type 2 gene: a possible contributor to the holoprosencephaly 3 phenotype." Mackay M., Fantes J., Scherer S., Boyle S., West K., Tsui L.-C., Belloni E., Lutz E., van Heyningen V., Harmar A.J. Genomics 37:345-353(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology." Wei Y., Mojsov S. J. Neuroendocrinol. 8:811-817(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adipose tissue.
[4]	"Structure of the human VIP2R gene for vasoactive intestinal peptide type 2 receptor." Lutz E.M., Shen S., Mackay M., West K., Harmar A.J. FEBS Lett. 458:197-203(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[9]	"Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals." Xia M., Sreedharan S.P., Goetzl E.J. J. Clin. Immunol. 16:21-30(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-318, FUNCTION, TISSUE SPECIFICITY. Tissue: T-cell.
[10]	"Crystal structure of the extracellular domain of human vasoactive intestinal polypeptide receptor 2." Structural genomics consortium (SGC) Submitted (MAR-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 26-118, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L36566 mRNA. Translation: AAC37569.1.
L40764 Genomic DNA. Translation: AAC41756.1.
U18810 mRNA. Translation: AAC50872.1.
X95097 mRNA. Translation: CAA64474.1.
Y18423 , Y18424, Y18425, Y18426, Y18427, Y18428, Y18429, Y18430, Y18431 Genomic DNA. Translation: CAB41899.1.
BT007118 mRNA. Translation: AAP35782.1.
CH236954 Genomic DNA. Translation: EAL23936.1.
CH471149 Genomic DNA. Translation: EAX04596.1.
BC010569 mRNA. Translation: AAH10569.1.

IPI

IPI00420122.

PIR

G02822.

RefSeq

NP_003373.2. NM_003382.4.

UniGene

Hs.585052.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X57	X-ray	2.10	A/B/C	26-118	[»]

ProteinModelPortal

P41587.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000262178.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P41587.

Polymorphism databases

DMDM

2506490.

Proteomic databases

PaxDb

P41587.

PRIDE

P41587.

Protocols and materials databases

DNASU

7434.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262178; ENSP00000262178; ENSG00000106018.

GeneID

7434.

KEGG

hsa:7434.

UCSC

uc003woh.3. human.

Organism-specific databases

CTD

7434.

GeneCards

GC07M158820.

H-InvDB

HIX0095225.
HIX0167627.

HGNC

HGNC:12695. VIPR2.

MIM

601970. gene.

neXtProt

NX_P41587.

Orphanet

3140. Schizophrenia.

PharmGKB

PA37314.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG265142.

HOGENOM

HOG000008249.

HOVERGEN

HBG008318.

KO

K04590.

PhylomeDB

P41587.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P41587.

Bgee

P41587.

CleanEx

HS_VIPR2.

Genevestigator

P41587.

GermOnline

ENSG00000106018. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR001571. GPCR_2_VIP_rcpt.
IPR002284. GPCR_2_VIP_rcpt_2.
[Graphical view]

PANTHER

PTHR12011:SF27. PTHR12011:SF27. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR00249. GPCRSECRETIN.
PR00491. VASOACTVEIPR.
PR01155. VIP2RECEPTOR.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P41587.

ChEMBL

CHEMBL4532.

ChiTaRS

VIPR2. human.

GenomeRNAi

7434.

NextBio

29118.

SOURCE

Search...

Entry information

Entry name

VIPR2_HUMAN

Accession

Primary (citable) accession number: P41587
Secondary accession number(s): Q13053 , Q15870, Q53Y09, Q9UCW0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.