Q92692 (PVRL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	538 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	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.11
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 process	Cell adhesion Host-virus interaction
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Host cell receptor for virus entry Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acrosome assembly Inferred from electronic annotation. Source: Compara 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: Compara cytoskeleton organization Inferred from electronic annotation. Source: Compara establishment of mitochondrion localization Inferred from electronic annotation. Source: Compara fertilization Inferred from electronic annotation. Source: Compara flagellum organization Inferred from electronic annotation. Source: Compara 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 directed against tumor cell target Inferred from mutant phenotype PubMed 12913096. Source: BHF-UCL sperm mitochondrion organization Inferred from electronic annotation. Source: Compara spermatid development Inferred from sequence or structural similarity. Source: BHF-UCL spermatid nucleus differentiation Inferred from electronic annotation. Source: Compara 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 viral entry into host cell via membrane fusion with the plasma membrane Inferred from direct assay PubMed 12915581. Source: BHF-UCL virion attachment, binding of host cell surface coreceptor Inferred from direct assay PubMed 12915581. Source: BHF-UCL
Cellular_component	cell surface Inferred from direct assay PubMed 16831868. Source: BHF-UCL integral to 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_function	coreceptor activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD226	Q15762	2	EBI-718419,EBI-4314442
PVRL3	Q9NQS3	2	EBI-718419,EBI-2826725

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Potential

Chain

32 – 538

507

Poliovirus receptor-related protein 2

PRO_0000015136

Regions

Topological domain

32 – 360

329

Extracellular Potential

Transmembrane

361 – 381

21

Helical; Potential

Topological domain

382 – 538

157

Cytoplasmic Potential

Domain

32 – 156

125

Ig-like V-type

Domain

162 – 256

95

Ig-like C2-type 1

Domain

261 – 345

85

Ig-like C2-type 2

Amino acid modifications

Modified residue

433

1

Phosphoserine Ref.10 Ref.12

Glycosylation

137

1

N-linked (GlcNAc...) Potential

Glycosylation

324

1

N-linked (GlcNAc...) Potential

Disulfide bond

54 ↔ 140

By similarity

Disulfide bond

183 ↔ 238

By similarity

Disulfide bond

283 ↔ 329

By similarity

Natural variations

Alternative sequence

351 – 479

129

NTAGA…GSPIP → RASPRDVGPLVWGAVGGTLL VLLLLAGGSLAFILLRVRRR RKSPGGAGGGASGDGGFYDP KAQVLGNGDPVFWTPVVPGP MEPDGKDEEEEEEEEKAEKG LMLPPPPALEDDMESQLDGS LISRRAVYV in isoform Alpha.

VSP_002628

Alternative sequence

480 – 538

59

Missing in isoform Alpha.

VSP_002629

Experimental info

Mutagenesis

89

1

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

Mutagenesis

89

1

M → I: Increased entry of HHV-1/Rid1 and HSV-2. Ref.8

Secondary structure

1

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538

Helix Strand Turn

Details...

Beta strand

35 – 37

3

Beta strand

40 – 43

4

Beta strand

50 – 52

3

Beta strand

55 – 58

4

Beta strand

64 – 71

8

Helix

77 – 79

3

Beta strand

81 – 86

6

Turn

87 – 89

3

Beta strand

90 – 92

3

Beta strand

95 – 98

4

Helix

100 – 102

3

Beta strand

103 – 107

5

Turn

113 – 115

3

Beta strand

125 – 127

3

Helix

132 – 134

3

Beta strand

136 – 145

10

Beta strand

148 – 157

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Delta [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 3AE4F83E92F6F624	FASTA	538	57,742
	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
	Isoform Alpha [UniParc]. Checksum: 870F08D7B9D896F2	FASTA	479	51,359
	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 RASPRDVGPL 370 380 390 400 410 420 VWGAVGGTLL VLLLLAGGSL AFILLRVRRR RKSPGGAGGG ASGDGGFYDP KAQVLGNGDP 430 440 450 460 470 VFWTPVVPGP MEPDGKDEEE EEEEEKAEKG LMLPPPPALE DDMESQLDGS LISRRAVYV

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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.
[12]	"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, MASS SPECTROMETRY. 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 , AF044962, AF044963, AF044964, AF044966, AF044967 Genomic DNA. Translation: AAC82348.1.
AF050154 Genomic DNA. Translation: AAD02503.1.

IPI

IPI00022661.
IPI00215980.

PIR

I68093.

RefSeq

NP_001036189.1. NM_001042724.1.
NP_002847.1. NM_002856.2.

UniGene

Hs.655455.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3R0N	X-ray	1.30	A	32-158	[»]
4DFH	X-ray	1.85	A/B	32-158	[»]
4DFI	X-ray	1.80	A	32-158	[»]
4HZA	X-ray	1.70	A/B	32-158	[»]

ProteinModelPortal

Q92692.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41043N.

IntAct

Q92692. 9 interactions.

MINT

MINT-90946.

STRING

9606.ENSP00000252483.

PTM databases

PhosphoSite

Q92692.

Polymorphism databases

DMDM

12643789.

Proteomic databases

PaxDb

Q92692.

PRIDE

Q92692.

Protocols and materials databases

DNASU

5819.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252483; ENSP00000252483; ENSG00000130202.
ENST00000252485; ENSP00000252485; ENSG00000130202.

GeneID

5819.

KEGG

hsa:5819.

UCSC

uc002ozv.3. human.
uc002ozw.1. human.

Organism-specific databases

CTD

5819.

GeneCards

GC19P045349.

HGNC

HGNC:9707. PVRL2.

HPA

CAB026138.
HPA012759.

MIM

600798. gene.

neXtProt

NX_Q92692.

PharmGKB

PA34052.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149530.

HOGENOM

HOG000237277.

HOVERGEN

HBG019169.

InParanoid

Q92692.

KO

K06531.

OMA

AFILLRV.

OrthoDB

EOG4PK281.

PhylomeDB

Q92692.

Enzyme and pathway databases

Reactome

REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q92692.

Bgee

Q92692.

CleanEx

HS_PVRL2.

Genevestigator

Q92692.

GermOnline

ENSG00000130202. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 3 hits.

InterPro

IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PVRL2. human.

EvolutionaryTrace

Q92692.

GenomeRNAi

5819.

NextBio

22666.

SOURCE

Search...

Entry information

Entry name

PVRL2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 137 of the entry and version 1 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.