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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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 141120ExtracellularSequence analysisAdd
BLAST
Transmembranei142 – 16221HelicalSequence analysisAdd
BLAST
Topological domaini163 – 24482CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421I → A: Abrogates interaction with PVR, cell clustering and PVR signaling. 1 Publication
Mutagenesisi42 – 421I → D: Abrogates interaction with PVR, cell clustering and PVR signaling. 1 Publication

Organism-specific databases

PharmGKBiPA164726482.

Polymorphism and mutation databases

BioMutaiTIGIT.
DMDMi121943253.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 244223T-cell immunoreceptor with Ig and ITIM domainsPRO_0000299405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi32 – 321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi45 ↔ 108PROSITE-ProRule annotation1 Publication
Glycosylationi101 – 1011N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ495A1.
PRIDEiQ495A1.

PTM databases

iPTMnetiQ495A1.
PhosphoSiteiQ495A1.

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

BgeeiQ495A1.
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
PVRL3Q9NQS32EBI-4314807,EBI-2826725
PVRL4Q96NY82EBI-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 interactions.
IntActiQ495A1. 5 interactions.
STRINGi9606.ENSP00000373167.

Structurei

Secondary structure

1
244
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 305Combined sources
Beta strandi33 – 364Combined sources
Beta strandi41 – 433Combined sources
Beta strandi45 – 495Combined sources
Beta strandi53 – 619Combined sources
Beta strandi64 – 707Combined sources
Turni71 – 733Combined sources
Beta strandi74 – 763Combined sources
Helixi79 – 813Combined sources
Turni82 – 843Combined sources
Beta strandi85 – 873Combined sources
Beta strandi93 – 953Combined sources
Helixi100 – 1023Combined sources
Beta strandi104 – 11310Combined sources
Beta strandi118 – 12710Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 22-129.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ495A1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 124103Ig-like V-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni32 – 4211HomodimerizationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi229 – 2346ITIM motif

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 CAI46183.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti103 – 1031T → A in AAI01289 (PubMed:15489334).Curated
Sequence conflicti117 – 1171T → A in BAC04973 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331I → V.
Corresponds to variant rs13098836 [ dbSNP | Ensembl ].
VAR_056079

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei167 – 1704KKAL → FVCF in isoform 2. 1 PublicationVSP_027634
Alternative sequencei171 – 24474Missing in isoform 2. 1 PublicationVSP_027635Add
BLAST

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]
XP_011510841.1. XM_011512539.1. [Q495A1-2]
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]
XP_011510841.1. XM_011512539.1. [Q495A1-2]
UniGeneiHs.421750.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 22-129.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128399. 4 interactions.
IntActiQ495A1. 5 interactions.
STRINGi9606.ENSP00000373167.

PTM databases

iPTMnetiQ495A1.
PhosphoSiteiQ495A1.

Polymorphism and mutation databases

BioMutaiTIGIT.
DMDMi121943253.

Proteomic databases

PaxDbiQ495A1.
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.
PharmGKBiPA164726482.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

EvolutionaryTraceiQ495A1.
GenomeRNAii201633.
PROiQ495A1.
SOURCEiSearch...

Gene expression databases

BgeeiQ495A1.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Spleen.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 21-244 (ISOFORM 2).
    Tissue: Lymph node.
  3. "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 1).
  4. "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: FUNCTION, INTERACTION WITH PVR; NECTIN2 AND NECTIN3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering."
    Stengel K.F., Harden-Bowles K., Yu X., Rouge L., Yin J., Comps-Agrar L., Wiesmann C., Bazan J.F., Eaton D.L., Grogan J.L.
    Proc. Natl. Acad. Sci. U.S.A. 109:5399-5404(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 23-128 ALONE AND IN COMPLEX WITH PVR, DISULFIDE BOND, SUBUNIT, MUTAGENESIS OF ILE-42.

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: June 8, 2016
This is version 101 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.