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Protein

T-cell immunoreceptor with Ig and ITIM domains

Gene

TIGIT

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

Functioni

Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cell recognition Source: GO_Central
  • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: GO_Central
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: GO_Central
  • negative regulation of interleukin-12 production Source: UniProtKB
  • negative regulation of T cell activation Source: UniProtKB
  • positive regulation of interleukin-10 production Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell immunoreceptor with Ig and ITIM domains
Alternative name(s):
V-set and immunoglobulin domain-containing protein 9
V-set and transmembrane domain-containing protein 3
Gene namesi
Name:TIGIT
Synonyms:VSIG9, VSTM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:26838. TIGIT.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 141ExtracellularSequence analysisAdd BLAST120
Transmembranei142 – 162HelicalSequence analysisAdd BLAST21
Topological domaini163 – 244CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

  • cell-cell adherens junction Source: GO_Central
  • cell surface Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42I → A: Abrogates interaction with PVR, cell clustering and PVR signaling. 1 Publication1
Mutagenesisi42I → D: Abrogates interaction with PVR, cell clustering and PVR signaling. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000181847.
PharmGKBiPA164726482.

Polymorphism and mutation databases

BioMutaiTIGIT.
DMDMi121943253.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000029940522 – 244T-cell immunoreceptor with Ig and ITIM domainsAdd BLAST223

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi45 ↔ 108PROSITE-ProRule annotation1 Publication
Glycosylationi101N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ495A1.
PeptideAtlasiQ495A1.
PRIDEiQ495A1.

PTM databases

iPTMnetiQ495A1.
PhosphoSitePlusiQ495A1.

Expressioni

Tissue specificityi

Expressed at low levels on peripheral memory and regulatory CD4+ T-cells and NK cells and is up-regulated following activation of these cells (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000181847.
CleanExiHS_TIGIT.
ExpressionAtlasiQ495A1. baseline and differential.
GenevisibleiQ495A1. HS.

Interactioni

Subunit structurei

Homodimer in cis; binds with high affinity to PVR, forming a heterotetrameric assembly of two TIGIT and two PVR molecules. Binds with lower affinity to NECTIN2 and NECTIN3.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CD226Q157624EBI-4314807,EBI-4314442
NECTIN3Q9NQS32EBI-4314807,EBI-2826725
NECTIN4Q96NY82EBI-4314807,EBI-4314784

GO - Molecular functioni

  • cell adhesion molecule binding Source: GO_Central
  • protein homodimerization activity Source: GO_Central
  • receptor binding Source: MGI

Protein-protein interaction databases

BioGridi128399. 4 interactors.
IntActiQ495A1. 5 interactors.
STRINGi9606.ENSP00000373167.

Structurei

Secondary structure

1244
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 30Combined sources5
Beta strandi33 – 36Combined sources4
Beta strandi41 – 43Combined sources3
Beta strandi45 – 49Combined sources5
Beta strandi53 – 61Combined sources9
Beta strandi64 – 70Combined sources7
Turni71 – 73Combined sources3
Beta strandi74 – 76Combined sources3
Helixi79 – 81Combined sources3
Turni82 – 84Combined sources3
Beta strandi85 – 87Combined sources3
Beta strandi93 – 95Combined sources3
Helixi100 – 102Combined sources3
Beta strandi104 – 113Combined sources10
Beta strandi118 – 127Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3Q0HX-ray1.70A/B22-137[»]
3RQ3X-ray2.70A/B22-137[»]
3UCRX-ray2.63A/B/C/D23-128[»]
3UDWX-ray2.90A/B20-128[»]
ProteinModelPortaliQ495A1.
SMRiQ495A1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ495A1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 124Ig-like V-typeAdd BLAST103

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni32 – 42HomodimerizationAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi229 – 234ITIM motif6

Domaini

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410JBCH. Eukaryota.
ENOG4111CNN. LUCA.
GeneTreeiENSGT00390000012671.
HOGENOMiHOG000154582.
HOVERGENiHBG096729.
InParanoidiQ495A1.
KOiK16350.
PhylomeDBiQ495A1.
TreeFamiTF338423.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[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 1 (identifier: Q495A1-1) [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
MRWCLLLIWA QGLRQAPLAS GMMTGTIETT GNISAEKGGS IILQCHLSST
60 70 80 90 100
TAQVTQVNWE QQDQLLAICN ADLGWHISPS FKDRVAPGPG LGLTLQSLTV
110 120 130 140 150
NDTGEYFCIY HTYPDGTYTG RIFLEVLESS VAEHGARFQI PLLGAMAATL
160 170 180 190 200
VVICTAVIVV VALTRKKKAL RIHSVEGDLR RKSAGQEEWS PSAPSPPGSC
210 220 230 240
VQAEAAPAGL CGEQRGEDCA ELHDYFNVLS YRSLGNCSFF TETG
Length:244
Mass (Da):26,319
Last modified:September 13, 2005 - v1
Checksum:iB890AF73F618C851
GO
Isoform 2 (identifier: Q495A1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     167-170: KKAL → FVCF
     171-244: Missing.

Show »
Length:170
Mass (Da):18,432
Checksum:i332F7049987C0803
GO

Sequence cautioni

The sequence CAI46183 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti103T → A in AAI01289 (PubMed:15489334).Curated1
Sequence conflicti117T → A in BAC04973 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05607933I → V.Corresponds to variant rs13098836dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_027634167 – 170KKAL → FVCF in isoform 2. 1 Publication4
Alternative sequenceiVSP_027635171 – 244Missing in isoform 2. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK097192 mRNA. Translation: BAC04973.1.
AL833175 mRNA. Translation: CAI46183.1. Different initiation.
BX640915 mRNA. Translation: CAE45956.1.
BC101288 mRNA. Translation: AAI01289.1.
BC101289 mRNA. Translation: AAI01290.1.
BC101290 mRNA. Translation: AAI01291.1.
BC101291 mRNA. Translation: AAI01292.1.
CCDSiCCDS2980.1. [Q495A1-1]
RefSeqiNP_776160.2. NM_173799.3. [Q495A1-1]
UniGeneiHs.421750.

Genome annotation databases

EnsembliENST00000383671; ENSP00000373167; ENSG00000181847. [Q495A1-1]
ENST00000486257; ENSP00000419085; ENSG00000181847. [Q495A1-1]
GeneIDi201633.
KEGGihsa:201633.
UCSCiuc003ebg.3. human. [Q495A1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK097192 mRNA. Translation: BAC04973.1.
AL833175 mRNA. Translation: CAI46183.1. Different initiation.
BX640915 mRNA. Translation: CAE45956.1.
BC101288 mRNA. Translation: AAI01289.1.
BC101289 mRNA. Translation: AAI01290.1.
BC101290 mRNA. Translation: AAI01291.1.
BC101291 mRNA. Translation: AAI01292.1.
CCDSiCCDS2980.1. [Q495A1-1]
RefSeqiNP_776160.2. NM_173799.3. [Q495A1-1]
UniGeneiHs.421750.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3Q0HX-ray1.70A/B22-137[»]
3RQ3X-ray2.70A/B22-137[»]
3UCRX-ray2.63A/B/C/D23-128[»]
3UDWX-ray2.90A/B20-128[»]
ProteinModelPortaliQ495A1.
SMRiQ495A1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128399. 4 interactors.
IntActiQ495A1. 5 interactors.
STRINGi9606.ENSP00000373167.

PTM databases

iPTMnetiQ495A1.
PhosphoSitePlusiQ495A1.

Polymorphism and mutation databases

BioMutaiTIGIT.
DMDMi121943253.

Proteomic databases

PaxDbiQ495A1.
PeptideAtlasiQ495A1.
PRIDEiQ495A1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000383671; ENSP00000373167; ENSG00000181847. [Q495A1-1]
ENST00000486257; ENSP00000419085; ENSG00000181847. [Q495A1-1]
GeneIDi201633.
KEGGihsa:201633.
UCSCiuc003ebg.3. human. [Q495A1-1]

Organism-specific databases

CTDi201633.
GeneCardsiTIGIT.
HGNCiHGNC:26838. TIGIT.
MIMi612859. gene.
neXtProtiNX_Q495A1.
OpenTargetsiENSG00000181847.
PharmGKBiPA164726482.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBCH. Eukaryota.
ENOG4111CNN. LUCA.
GeneTreeiENSGT00390000012671.
HOGENOMiHOG000154582.
HOVERGENiHBG096729.
InParanoidiQ495A1.
KOiK16350.
PhylomeDBiQ495A1.
TreeFamiTF338423.

Miscellaneous databases

EvolutionaryTraceiQ495A1.
GenomeRNAii201633.
PROiQ495A1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181847.
CleanExiHS_TIGIT.
ExpressionAtlasiQ495A1. baseline and differential.
GenevisibleiQ495A1. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTIGIT_HUMAN
AccessioniPrimary (citable) accession number: Q495A1
Secondary accession number(s): Q495A3
, Q5JPD8, Q6MZS2, Q8N877
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: September 13, 2005
Last modified: November 2, 2016
This is version 105 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 chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.