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Protein

Nectin-2

Gene

NECTIN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive (PubMed:26755705). Probable cell adhesion protein (PubMed:9657005).2 Publications
(Microbial infection) Acts as a receptor for herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV).2 Publications

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • coreceptor activity Source: ProtInc
  • protein homodimerization activity Source: BHF-UCL
  • receptor binding Source: GO_Central
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • acrosome assembly Source: Ensembl
  • adherens junction organization Source: Reactome
  • adhesion of symbiont to host Source: BHF-UCL
  • cell part morphogenesis Source: Ensembl
  • cell recognition Source: GO_Central
  • cilium organization Source: Ensembl
  • coreceptor-mediated virion attachment to host cell Source: BHF-UCL
  • cytoskeleton organization Source: Ensembl
  • establishment of mitochondrion localization Source: Ensembl
  • fertilization Source: Ensembl
  • fusion of virus membrane with host plasma membrane Source: BHF-UCL
  • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: GO_Central
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: BHF-UCL
  • positive regulation of immunoglobulin mediated immune response Source: BHF-UCL
  • positive regulation of mast cell activation Source: BHF-UCL
  • positive regulation of natural killer cell mediated cytotoxicity Source: BHF-UCL
  • positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Source: BHF-UCL
  • regulation of immune response Source: Reactome
  • regulation of viral entry into host cell Source: CACAO
  • spermatid development Source: BHF-UCL
  • spermatid nucleus differentiation Source: Ensembl
  • sperm mitochondrion organization Source: Ensembl
  • susceptibility to natural killer cell mediated cytotoxicity Source: BHF-UCL
  • susceptibility to T cell mediated cytotoxicity Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Cell adhesion, Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130202-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-418990. Adherens junctions interactions.
R-HSA-420597. Nectin/Necl trans heterodimerization.

Names & Taxonomyi

Protein namesi
Recommended name:
Nectin-2
Alternative name(s):
Herpes virus entry mediator B
Short name:
Herpesvirus entry mediator B
Short name:
HveB
Nectin cell adhesion molecule 2Imported
Poliovirus receptor-related protein 2
CD_antigen: CD112
Gene namesi
Name:NECTIN2Imported
Synonyms:HVEB, PRR2, PVRL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:9707. NECTIN2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 360ExtracellularSequence analysisAdd BLAST329
Transmembranei361 – 381HelicalSequence analysisAdd BLAST21
Topological domaini382 – 538CytoplasmicSequence analysisAdd BLAST157

GO - Cellular componenti

  • cell-cell adherens junction Source: GO_Central
  • cell-cell contact zone Source: Ensembl
  • cell-cell junction Source: BHF-UCL
  • cell surface Source: BHF-UCL
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • integral component of membrane Source: BHF-UCL
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: Reactome
  • zonula adherens Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi81N → A: Abolishes homodimerization. 1 Publication1
Mutagenesisi89M → F: Loss of entry of HHV-1/Rid1 and HSV-2. No effect on PRV entry. 1 Publication1
Mutagenesisi89M → I: Increased entry of HHV-1/Rid1 and HSV-2. 1 Publication1

Organism-specific databases

DisGeNETi5819.
OpenTargetsiENSG00000130202.
PharmGKBiPA34052.

Polymorphism and mutation databases

BioMutaiPVRL2.
DMDMi12643789.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000001513632 – 538Nectin-2Add BLAST507

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 140PROSITE-ProRule annotation1 Publication
Glycosylationi137N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi183 ↔ 238PROSITE-ProRule annotation
Disulfide bondi283 ↔ 329PROSITE-ProRule annotation
Glycosylationi324N-linked (GlcNAc...)Sequence analysis1
Modified residuei410PhosphothreonineCombined sources1
Modified residuei433PhosphoserineCombined sources1
Isoform Alpha (identifier: Q92692-2)
Modified residuei465PhosphoserineCombined sourcesCurated1
Modified residuei470PhosphoserineCombined sourcesCurated1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ92692.
MaxQBiQ92692.
PaxDbiQ92692.
PeptideAtlasiQ92692.
PRIDEiQ92692.

PTM databases

iPTMnetiQ92692.
PhosphoSitePlusiQ92692.
SwissPalmiQ92692.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000130202.
CleanExiHS_PVRL2.
ExpressionAtlasiQ92692. baseline and differential.
GenevisibleiQ92692. HS.

Organism-specific databases

HPAiCAB026138.
HPA012759.

Interactioni

Subunit structurei

Can form trans-heterodimers with NECTIN3 (By similarity). Interacts with CD226 or with PVRIG; these interactions are competitive and have a differential functional outcome on T-cell activation, either positive or negative, respectively. Binds with low affinity to TIGIT.By similarity3 Publications
(Microbial infection) Interacts with herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV) envelope glycoprotein D (PubMed:11602758, PubMed:9657005).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-718419,EBI-718419
CD226Q157622EBI-718419,EBI-4314442
KRTAP10-5P603703EBI-718419,EBI-10172150
KRTAP10-7P604093EBI-718419,EBI-10172290
KRTAP5-9P263713EBI-718419,EBI-3958099
MDFIQ997504EBI-718419,EBI-724076
MLLT4P551962EBI-718419,EBI-365875
NECTIN3Q9NQS33EBI-718419,EBI-2826725
NOTCH2NLQ7Z3S93EBI-718419,EBI-945833
SIAH1Q8IUQ43EBI-718419,EBI-747107

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi111777. 33 interactors.
DIPiDIP-41043N.
IntActiQ92692. 30 interactors.
MINTiMINT-90946.
STRINGi9606.ENSP00000252483.

Structurei

Secondary structure

1538
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 37Combined sources3
Beta strandi40 – 43Combined sources4
Beta strandi50 – 52Combined sources3
Beta strandi55 – 58Combined sources4
Beta strandi64 – 71Combined sources8
Helixi77 – 79Combined sources3
Beta strandi81 – 86Combined sources6
Turni87 – 89Combined sources3
Beta strandi90 – 92Combined sources3
Beta strandi95 – 98Combined sources4
Helixi100 – 102Combined sources3
Beta strandi103 – 107Combined sources5
Turni113 – 115Combined sources3
Beta strandi125 – 127Combined sources3
Helixi132 – 134Combined sources3
Beta strandi136 – 145Combined sources10
Beta strandi148 – 157Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3R0NX-ray1.30A32-158[»]
4DFHX-ray1.85A/B32-158[»]
4DFIX-ray1.80A32-158[»]
4HZAX-ray1.70A/B32-158[»]
ProteinModelPortaliQ92692.
SMRiQ92692.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92692.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 156Ig-like V-typeAdd BLAST125
Domaini162 – 256Ig-like C2-type 1Add BLAST95
Domaini261 – 345Ig-like C2-type 2Add BLAST85

Sequence similaritiesi

Belongs to the nectin family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIB8. Eukaryota.
ENOG4111FZM. LUCA.
GeneTreeiENSGT00770000120512.
HOGENOMiHOG000237277.
HOVERGENiHBG019169.
InParanoidiQ92692.
KOiK06531.
OMAiREVTWLR.
OrthoDBiEOG091G0CPW.
PhylomeDBiQ92692.
TreeFamiTF331051.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR033318. Nectin-2.
[Graphical view]
PANTHERiPTHR23277:SF63. PTHR23277:SF63. 1 hit.
PfamiPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Delta (identifier: Q92692-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MARAAALLPS RSPPTPLLWP LLLLLLLETG AQDVRVQVLP EVRGQLGGTV
60 70 80 90 100
ELPCHLLPPV PGLYISLVTW QRPDAPANHQ NVAAFHPKMG PSFPSPKPGS
110 120 130 140 150
ERLSFVSAKQ STGQDTEAEL QDATLALHGL TVEDEGNYTC EFATFPKGSV
160 170 180 190 200
RGMTWLRVIA KPKNQAEAQK VTFSQDPTTV ALCISKEGRP PARISWLSSL
210 220 230 240 250
DWEAKETQVS GTLAGTVTVT SRFTLVPSGR ADGVTVTCKV EHESFEEPAL
260 270 280 290 300
IPVTLSVRYP PEVSISGYDD NWYLGRTDAT LSCDVRSNPE PTGYDWSTTS
310 320 330 340 350
GTFPTSAVAQ GSQLVIHAVD SLFNTTFVCT VTNAVGMGRA EQVIFVRETP
360 370 380 390 400
NTAGAGATGG IIGGIIAAII ATAVAATGIL ICRQQRKEQT LQGAEEDEDL
410 420 430 440 450
EGPPSYKPPT PKAKLEAQEM PSQLFTLGAS EHSPLKTPYF DAGASCTEQE
460 470 480 490 500
MPRYHELPTL EERSGPLHPG ATSLGSPIPV PPGPPAVEDV SLDLEDEEGE
510 520 530
EEEEYLDKIN PIYDALSYSS PSDSYQGKGF VMSRAMYV
Length:538
Mass (Da):57,742
Last modified:February 1, 1997 - v1
Checksum:i3AE4F83E92F6F624
GO
Isoform Alpha (identifier: Q92692-2) [UniParc]FASTAAdd to basket

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

Show »
Length:479
Mass (Da):51,359
Checksum:i870F08D7B9D896F2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform Alpha (identifier: Q92692-2)
Sequence conflicti410P → L in BAF84019 (PubMed:14702039).Combined sourcesCurated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002628351 – 479NTAGA…GSPIP → RASPRDVGPLVWGAVGGTLL VLLLLAGGSLAFILLRVRRR RKSPGGAGGGASGDGGFYDP KAQVLGNGDPVFWTPVVPGP MEPDGKDEEEEEEEEKAEKG LMLPPPPALEDDMESQLDGS LISRRAVYV in isoform Alpha. 4 PublicationsAdd BLAST129
Alternative sequenceiVSP_002629480 – 538Missing in isoform Alpha. 4 PublicationsAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80038 mRNA. Translation: CAA56342.1.
AF058448 mRNA. Translation: AAC23797.1.
AK291330 mRNA. Translation: BAF84019.1.
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.
CCDSiCCDS12645.1. [Q92692-2]
CCDS42576.1. [Q92692-1]
PIRiI68093.
RefSeqiNP_001036189.1. NM_001042724.1. [Q92692-1]
NP_002847.1. NM_002856.2. [Q92692-2]
UniGeneiHs.655455.

Genome annotation databases

EnsembliENST00000252483; ENSP00000252483; ENSG00000130202. [Q92692-1]
ENST00000252485; ENSP00000252485; ENSG00000130202. [Q92692-2]
GeneIDi5819.
KEGGihsa:5819.
UCSCiuc002ozv.4. human. [Q92692-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80038 mRNA. Translation: CAA56342.1.
AF058448 mRNA. Translation: AAC23797.1.
AK291330 mRNA. Translation: BAF84019.1.
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.
CCDSiCCDS12645.1. [Q92692-2]
CCDS42576.1. [Q92692-1]
PIRiI68093.
RefSeqiNP_001036189.1. NM_001042724.1. [Q92692-1]
NP_002847.1. NM_002856.2. [Q92692-2]
UniGeneiHs.655455.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3R0NX-ray1.30A32-158[»]
4DFHX-ray1.85A/B32-158[»]
4DFIX-ray1.80A32-158[»]
4HZAX-ray1.70A/B32-158[»]
ProteinModelPortaliQ92692.
SMRiQ92692.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111777. 33 interactors.
DIPiDIP-41043N.
IntActiQ92692. 30 interactors.
MINTiMINT-90946.
STRINGi9606.ENSP00000252483.

PTM databases

iPTMnetiQ92692.
PhosphoSitePlusiQ92692.
SwissPalmiQ92692.

Polymorphism and mutation databases

BioMutaiPVRL2.
DMDMi12643789.

Proteomic databases

EPDiQ92692.
MaxQBiQ92692.
PaxDbiQ92692.
PeptideAtlasiQ92692.
PRIDEiQ92692.

Protocols and materials databases

DNASUi5819.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252483; ENSP00000252483; ENSG00000130202. [Q92692-1]
ENST00000252485; ENSP00000252485; ENSG00000130202. [Q92692-2]
GeneIDi5819.
KEGGihsa:5819.
UCSCiuc002ozv.4. human. [Q92692-1]

Organism-specific databases

CTDi5819.
DisGeNETi5819.
GeneCardsiPVRL2.
HGNCiHGNC:9707. NECTIN2.
HPAiCAB026138.
HPA012759.
MIMi600798. gene.
neXtProtiNX_Q92692.
OpenTargetsiENSG00000130202.
PharmGKBiPA34052.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIB8. Eukaryota.
ENOG4111FZM. LUCA.
GeneTreeiENSGT00770000120512.
HOGENOMiHOG000237277.
HOVERGENiHBG019169.
InParanoidiQ92692.
KOiK06531.
OMAiREVTWLR.
OrthoDBiEOG091G0CPW.
PhylomeDBiQ92692.
TreeFamiTF331051.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130202-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-418990. Adherens junctions interactions.
R-HSA-420597. Nectin/Necl trans heterodimerization.

Miscellaneous databases

ChiTaRSiPVRL2. human.
EvolutionaryTraceiQ92692.
GeneWikiiPVRL2.
GenomeRNAii5819.
PROiQ92692.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130202.
CleanExiHS_PVRL2.
ExpressionAtlasiQ92692. baseline and differential.
GenevisibleiQ92692. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR033318. Nectin-2.
[Graphical view]
PANTHERiPTHR23277:SF63. PTHR23277:SF63. 1 hit.
PfamiPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNECT2_HUMAN
AccessioniPrimary (citable) accession number: Q92692
Secondary accession number(s): A8K5L5
, O75455, Q6IBI6, Q96J29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 174 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.