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Protein

Nectin-2

Gene

NECTIN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: BHF-UCL
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processCell adhesion, Host-virus interaction

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000130202.9
HGNCiHGNC:9707 NECTIN2
MIMi600798 gene
neXtProtiNX_Q92692

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Disulfide bondi183 ↔ 238PROSITE-ProRule annotation
Disulfide bondi283 ↔ 329PROSITE-ProRule annotation
Glycosylationi324N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi75411
75412 [Q92692-2]

PTM databases

GlyConnecti1537
iPTMnetiQ92692
PhosphoSitePlusiQ92692
SwissPalmiQ92692

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000130202 Expressed in 214 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_PVRL2
ExpressionAtlasiQ92692 baseline and differential
GenevisibleiQ92692 HS

Organism-specific databases

HPAiCAB026138
HPA012759
HPA073459

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111777, 43 interactors
DIPiDIP-41043N
IntActiQ92692, 37 interactors
MINTiQ92692
STRINGi9606.ENSP00000252483

Structurei

Secondary structure

1538
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00900000140811
HOGENOMiHOG000237277
HOVERGENiHBG019169
InParanoidiQ92692
KOiK06531
OMAiKDDMESH
OrthoDBiEOG091G0CPW
PhylomeDBiQ92692
TreeFamiTF331051

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR033318 Nectin-2
PANTHERiPTHR23277:SF63 PTHR23277:SF63, 1 hit
PfamiView protein in Pfam
PF08205 C2-set_2, 1 hit
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 2 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EKE8K7EKE8_HUMAN
Nectin-2
NECTIN2
210Annotation score:
K7EK87K7EK87_HUMAN
Nectin-2
NECTIN2
56Annotation score:
K7ERL3K7ERL3_HUMAN
Nectin-2
NECTIN2
54Annotation score:

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

Similar proteinsi

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[»]
5V52X-ray3.10C/D32-158[»]
ProteinModelPortaliQ92692
SMRiQ92692
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111777, 43 interactors
DIPiDIP-41043N
IntActiQ92692, 37 interactors
MINTiQ92692
STRINGi9606.ENSP00000252483

PTM databases

GlyConnecti1537
iPTMnetiQ92692
PhosphoSitePlusiQ92692
SwissPalmiQ92692

Polymorphism and mutation databases

BioMutaiPVRL2
DMDMi12643789

Proteomic databases

EPDiQ92692
MaxQBiQ92692
PaxDbiQ92692
PeptideAtlasiQ92692
PRIDEiQ92692
ProteomicsDBi75411
75412 [Q92692-2]

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
EuPathDBiHostDB:ENSG00000130202.9
GeneCardsiNECTIN2
HGNCiHGNC:9707 NECTIN2
HPAiCAB026138
HPA012759
HPA073459
MIMi600798 gene
neXtProtiNX_Q92692
OpenTargetsiENSG00000130202
PharmGKBiPA34052
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIB8 Eukaryota
ENOG4111FZM LUCA
GeneTreeiENSGT00900000140811
HOGENOMiHOG000237277
HOVERGENiHBG019169
InParanoidiQ92692
KOiK06531
OMAiKDDMESH
OrthoDBiEOG091G0CPW
PhylomeDBiQ92692
TreeFamiTF331051

Enzyme and pathway databases

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

ChiTaRSiNECTIN2 human
EvolutionaryTraceiQ92692
GeneWikiiPVRL2
GenomeRNAii5819
PROiPR:Q92692
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130202 Expressed in 214 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_PVRL2
ExpressionAtlasiQ92692 baseline and differential
GenevisibleiQ92692 HS

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR033318 Nectin-2
PANTHERiPTHR23277:SF63 PTHR23277:SF63, 1 hit
PfamiView protein in Pfam
PF08205 C2-set_2, 1 hit
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 2 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiNECT2_HUMAN
AccessioniPrimary (citable) accession number: Q92692
Secondary accession number(s): A8K5L5
, O75455, Q6IBI6, Q96J29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 1, 1997
Last modified: November 7, 2018
This is version 193 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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