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Q92692 (PVRL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Poliovirus receptor-related protein 2
Alternative name(s):
Herpes virus entry mediator B
Short name=Herpesvirus entry mediator B
Short name=HveB
Nectin-2
CD_antigen=CD112
Gene names
Name:PVRL2
Synonyms:HVEB, PRR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length538 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable cell adhesion protein. Ref.2

Subunit structure

Can form trans-heterodimers with PVRL3/nectin-3 By similarity. Interacts with CD226. Binds with low affinity to TIGIT. Interacts with herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV) envelope glycoprotein D; functions as an entry receptor for these viruses. Ref.8 Ref.9 Ref.12

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Ubiquitous.

Sequence similarities

Belongs to the nectin family.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processCell adhesion
Host-virus interaction
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionHost cell receptor for virus entry
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacrosome assembly

Inferred from electronic annotation. Source: Ensembl

adherens junction organization

Traceable author statement. Source: Reactome

adhesion to symbiont

Inferred from direct assay PubMed 12915581. Source: BHF-UCL

cell junction assembly

Traceable author statement. Source: Reactome

cell part morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell-cell junction organization

Traceable author statement. Source: Reactome

cilium organization

Inferred from electronic annotation. Source: Ensembl

coreceptor-mediated virion attachment to host cell

Inferred from direct assay PubMed 12915581. Source: BHF-UCL

cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

establishment of mitochondrion localization

Inferred from electronic annotation. Source: Ensembl

fertilization

Inferred from electronic annotation. Source: Ensembl

fusion of virus membrane with host plasma membrane

Inferred from direct assay PubMed 12915581. Source: BHF-UCL

homophilic cell adhesion

Inferred from direct assay PubMed 9845526. Source: BHF-UCL

positive regulation of immunoglobulin mediated immune response

Inferred from mutant phenotype PubMed 16831868. Source: BHF-UCL

positive regulation of mast cell activation

Inferred from mutant phenotype PubMed 16831868. Source: BHF-UCL

positive regulation of natural killer cell mediated cytotoxicity

Inferred from mutant phenotype PubMed 16304049. Source: BHF-UCL

positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target

Inferred from mutant phenotype PubMed 12913096. Source: BHF-UCL

regulation of immune response

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement Ref.2. Source: GOC

sperm mitochondrion organization

Inferred from electronic annotation. Source: Ensembl

spermatid development

Inferred from sequence or structural similarity. Source: BHF-UCL

spermatid nucleus differentiation

Inferred from electronic annotation. Source: Ensembl

susceptibility to T cell mediated cytotoxicity

Inferred from direct assay PubMed 15039383. Source: BHF-UCL

susceptibility to natural killer cell mediated cytotoxicity

Inferred from mutant phenotype PubMed 12913096. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from direct assay PubMed 16831868. Source: BHF-UCL

cell-cell junction

Inferred from direct assay PubMed 9845526. Source: BHF-UCL

integral component of membrane

Inferred from direct assay PubMed 12913096. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

zonula adherens

Inferred from sequence or structural similarity PubMed 10225955. Source: BHF-UCL

   Molecular_functioncell adhesion molecule binding

Inferred from physical interaction PubMed 12913096PubMed 9845526. Source: BHF-UCL

coreceptor activity

Traceable author statement Ref.2. Source: ProtInc

identical protein binding

Inferred from physical interaction PubMed 21982860PubMed 23758976. Source: IntAct

protein homodimerization activity

Inferred from physical interaction PubMed 9845526PubMed 9845526. Source: BHF-UCL

virus receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Delta (identifier: Q92692-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Alpha (identifier: Q92692-2)

The sequence of this isoform differs from the canonical sequence as follows:
     351-479: NTAGAGATGG...GATSLGSPIP → RASPRDVGPL...SLISRRAVYV
     480-538: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 538507Poliovirus receptor-related protein 2
PRO_0000015136

Regions

Topological domain32 – 360329Extracellular Potential
Transmembrane361 – 38121Helical; Potential
Topological domain382 – 538157Cytoplasmic Potential
Domain32 – 156125Ig-like V-type
Domain162 – 25695Ig-like C2-type 1
Domain261 – 34585Ig-like C2-type 2

Amino acid modifications

Modified residue4331Phosphoserine Ref.10 Ref.13
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation3241N-linked (GlcNAc...) Potential
Disulfide bond54 ↔ 140 By similarity
Disulfide bond183 ↔ 238 By similarity
Disulfide bond283 ↔ 329 By similarity

Natural variations

Alternative sequence351 – 479129NTAGA…GSPIP → RASPRDVGPLVWGAVGGTLL VLLLLAGGSLAFILLRVRRR RKSPGGAGGGASGDGGFYDP KAQVLGNGDPVFWTPVVPGP MEPDGKDEEEEEEEEKAEKG LMLPPPPALEDDMESQLDGS LISRRAVYV in isoform Alpha.
VSP_002628
Alternative sequence480 – 53859Missing in isoform Alpha.
VSP_002629

Experimental info

Mutagenesis891M → F: Loss of entry of HHV-1/Rid1 and HSV-2. No effect on PRV entry. Ref.8
Mutagenesis891M → I: Increased entry of HHV-1/Rid1 and HSV-2. Ref.8

Secondary structure

................................ 538
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Delta [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 3AE4F83E92F6F624

FASTA53857,742
        10         20         30         40         50         60 
MARAAALLPS RSPPTPLLWP LLLLLLLETG AQDVRVQVLP EVRGQLGGTV ELPCHLLPPV 

        70         80         90        100        110        120 
PGLYISLVTW QRPDAPANHQ NVAAFHPKMG PSFPSPKPGS ERLSFVSAKQ STGQDTEAEL 

       130        140        150        160        170        180 
QDATLALHGL TVEDEGNYTC EFATFPKGSV RGMTWLRVIA KPKNQAEAQK VTFSQDPTTV 

       190        200        210        220        230        240 
ALCISKEGRP PARISWLSSL DWEAKETQVS GTLAGTVTVT SRFTLVPSGR ADGVTVTCKV 

       250        260        270        280        290        300 
EHESFEEPAL IPVTLSVRYP PEVSISGYDD NWYLGRTDAT LSCDVRSNPE PTGYDWSTTS 

       310        320        330        340        350        360 
GTFPTSAVAQ GSQLVIHAVD SLFNTTFVCT VTNAVGMGRA EQVIFVRETP NTAGAGATGG 

       370        380        390        400        410        420 
IIGGIIAAII ATAVAATGIL ICRQQRKEQT LQGAEEDEDL EGPPSYKPPT PKAKLEAQEM 

       430        440        450        460        470        480 
PSQLFTLGAS EHSPLKTPYF DAGASCTEQE MPRYHELPTL EERSGPLHPG ATSLGSPIPV 

       490        500        510        520        530 
PPGPPAVEDV SLDLEDEEGE EEEEYLDKIN PIYDALSYSS PSDSYQGKGF VMSRAMYV 

« Hide

Isoform Alpha [UniParc].

Checksum: 870F08D7B9D896F2
Show »

FASTA47951,359

References

« Hide 'large scale' references
[1]"The human PRR2 gene, related to the human poliovirus receptor gene (PVR), is the true homolog of the murine MPH gene."
Eberle F., Dubreuil P., Mattei M.-G., Devilard E., Lopez M.
Gene 159:267-272(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA).
[2]"A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus."
Warner M.S., Geraghty R.J., Martinez W.M., Montgomery R.I., Whitbeck J.C., Xu R., Eisenberg R.J., Cohen G.H., Spear P.G.
Virology 246:179-189(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION AS A RECEPTOR FOR MUTANTS OF HHV-1; HHV-2 AND PRV.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
[4]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. expand/collapse author list , 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].
[5]"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] (ISOFORM ALPHA).
Tissue: Brain.
[6]"A transcriptional map in the region of 19q13 derived using direct sequencing and exon trapping."
Yoshiura K., Murray J.C.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-538.
[7]"Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1."
Freitas E.M., Zhang W.J., Lalonde J.P., Tay G.K., Gaudieri S., Ashworth L.K., Van Bockxmeer F.M., Dawkins R.L.
DNA Seq. 9:89-100(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 449-538.
[8]"Structural features of nectin-2 (HveB) required for herpes simplex virus entry."
Martinez W.M., Spear P.G.
J. Virol. 75:11185-11195(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HHV-1 MUTANT RID1; HHV-2 AND PRV GLYCOPROTEIN D, MUTAGENESIS OF MET-89.
[9]"PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis."
Pende D., Bottino C., Castriconi R., Cantoni C., Marcenaro S., Rivera P., Spaggiari G.M., Dondero A., Carnemolla B., Reymond N., Mingari M.C., Lopez M., Moretta L., Moretta A.
Mol. Immunol. 42:463-469(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD226.
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells."
Yu X., Harden K., Gonzalez L.C., Francesco M., Chiang E., Irving B., Tom I., Ivelja S., Refino C.J., Clark H., Eaton D., Grogan J.L.
Nat. Immunol. 10:48-57(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TIGIT.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X80038 mRNA. Translation: CAA56342.1.
AF058448 mRNA. Translation: AAC23797.1.
CR456818 mRNA. Translation: CAG33099.1.
CH471126 Genomic DNA. Translation: EAW57298.1.
BC003091 mRNA. Translation: AAH03091.1.
AF044968 expand/collapse EMBL AC list , AF044962, AF044963, AF044964, AF044966, AF044967 Genomic DNA. Translation: AAC82348.1.
AF050154 Genomic DNA. Translation: AAD02503.1.
PIRI68093.
RefSeqNP_001036189.1. NM_001042724.1.
NP_002847.1. NM_002856.2.
UniGeneHs.655455.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3R0NX-ray1.30A32-158[»]
4DFHX-ray1.85A/B32-158[»]
4DFIX-ray1.80A32-158[»]
4HZAX-ray1.70A/B32-158[»]
ProteinModelPortalQ92692.
SMRQ92692. Positions 32-350.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111777. 14 interactions.
DIPDIP-41043N.
IntActQ92692. 14 interactions.
MINTMINT-90946.
STRING9606.ENSP00000252483.

PTM databases

PhosphoSiteQ92692.

Polymorphism databases

DMDM12643789.

Proteomic databases

PaxDbQ92692.
PRIDEQ92692.

Protocols and materials databases

DNASU5819.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252483; ENSP00000252483; ENSG00000130202. [Q92692-1]
ENST00000252485; ENSP00000252485; ENSG00000130202. [Q92692-2]
GeneID5819.
KEGGhsa:5819.
UCSCuc002ozv.3. human. [Q92692-2]
uc002ozw.1. human. [Q92692-1]

Organism-specific databases

CTD5819.
GeneCardsGC19P045349.
HGNCHGNC:9707. PVRL2.
HPACAB026138.
HPA012759.
MIM600798. gene.
neXtProtNX_Q92692.
PharmGKBPA34052.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149530.
HOGENOMHOG000237277.
HOVERGENHBG019169.
InParanoidQ92692.
KOK06531.
OMAREVTWLR.
OrthoDBEOG7D59N6.
PhylomeDBQ92692.
TreeFamTF331051.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ92692.
BgeeQ92692.
CleanExHS_PVRL2.
GenevestigatorQ92692.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPVRL2. human.
EvolutionaryTraceQ92692.
GeneWikiPVRL2.
GenomeRNAi5819.
NextBio22666.
PROQ92692.
SOURCESearch...

Entry information

Entry namePVRL2_HUMAN
AccessionPrimary (citable) accession number: Q92692
Secondary accession number(s): O75455, Q6IBI6, Q96J29
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries