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TIGIT Gene

protein-coding   GIFtS: 49
GCID: GC03P113995

T Cell Immunoreceptor With Ig And ITIM Domains

(Previous names: V-set and immunoglobulin domain containing 9, V-set and...)
(Previous symbols: VSIG9, VSTM3)
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
T Cell Immunoreceptor With Ig And ITIM Domains1 2     V-Set And Immunoglobulin Domain-Containing Protein 92 3
VSIG91 2 3     V-Set And Transmembrane Domain-Containing Protein 32 3
VSTM31 2 3     WUCAM2
V-Set And Immunoglobulin Domain Containing 91 2     T-Cell Immunoreceptor With Ig And ITIM Domains2
V-Set And Transmembrane Domain Containing 31 2     Washington University Cell Adhesion Molecule2

External Ids:    HGNC: 268381   Entrez Gene: 2016332   Ensembl: ENSG000001818477   OMIM: 6128595   UniProtKB: Q495A13   

Export aliases for TIGIT gene to outside databases

Previous GC identifers: GC03P115496 GC03P111385


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TIGIT Gene:
This gene encodes a member of the PVR (poliovirus receptor) family of immunoglobin proteins. The product of this
gene is expressed on several classes of T cells including follicular B helper T cells (TFH). The protein has been
shown to bind PVR with high affinity; this binding is thought to assist interactions between TFH and dendritic
cells to regulate T cell dependent B cell responses.(provided by RefSeq, Sep 2009)

GeneCards Summary for TIGIT Gene:
TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a protein-coding gene. GO annotations related to this gene include receptor binding.

UniProtKB/Swiss-Prot: TIGIT_HUMAN, Q495A1
Function: 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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000003.11  NT_005612.17  NC_018914.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TIGIT gene promoter:
         AML1a   HNF-4alpha2   GATA-1   HNF-4alpha1   PPAR-gamma1   FOXJ2 (long isoform)   Chx10   PPAR-gamma2   FOXJ2   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTIGIT promoter sequence
   Search Chromatin IP Primers for TIGIT

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TIGIT


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3q13.31   Ensembl cytogenetic band:  3q13.31   HGNC cytogenetic band: 3q13.31

TIGIT Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TIGIT gene location

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P113995:  view genomic region     (about GC identifiers)

Start:
113,995,760 bp from pter      End:
114,029,135 bp from pter
Size:
33,376 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: TIGIT_HUMAN, Q495A1 (See protein sequence)
Recommended Name: T-cell immunoreceptor with Ig and ITIM domains precursor  
Size: 244 amino acids; 26319 Da
Subunit: 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 PVRL2 and PVRL3
Sequence caution: Sequence=CAI46183.1; Type=Erroneous initiation;
4 PDB 3D structures from and Proteopedia for TIGIT:
3Q0H (3D)        3RQ3 (3D)        3UCR (3D)        3UDW (3D)    
Secondary accessions: Q495A3 Q5JPD8 Q6MZS2 Q8N877
Alternative splicing: 2 isoforms:  Q495A1-1   Q495A1-2   

Explore the universe of human proteins at neXtProt for TIGIT: NX_Q495A1

Explore proteomics data for TIGIT at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn32, Asn101
  • Modification sites at PhosphoSitePlus

  • See TIGIT Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_776160.2  
    ENSEMBL proteins: 
     ENSP00000418917   ENSP00000420552   ENSP00000419085   ENSP00000419706   ENSP00000373167  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    VSET: Immunoglobulin superfamily / V-set domain containing

    4 InterPro protein domains:
     IPR007110 Ig-like_dom
     IPR003599 Ig_sub
     IPR013783 Ig-like_fold
     IPR013106 Ig_V-set

    Graphical View of Domain Structure for InterPro Entry Q495A1

    ProtoNet protein and cluster: Q495A1

    UniProtKB/Swiss-Prot: TIGIT_HUMAN, Q495A1
    Domain: Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor
    motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind
    the SH2 domain of several SH2-containing phosphatases
    Similarity: Contains 1 Ig-like V-type (immunoglobulin-like) domain


    Find genes that share domains with TIGIT           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TIGIT_HUMAN, Q495A1
    Function: 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

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005102receptor binding IPI19011627
    GO:0005515protein binding IPI19011627
         
    Find genes that share ontologies with TIGIT           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Tigit):
     hematopoietic system  immune system 

    Find genes that share phenotypes with TIGIT           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Tigittm1Sdl for TIGIT

       genOway: Develop your customized and physiologically relevant rodent model for TIGIT

    miRNA
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    hsa-miR-4264 hsa-miR-130a* hsa-miR-3120-3p hsa-miR-545 hsa-miR-23c hsa-miR-455-3p hsa-miR-33a* hsa-miR-942
    SwitchGear 3'UTR luciferase reporter plasmidTIGIT 3' UTR sequence
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TIGIT_HUMAN, Q495A1: Cell membrane; Single-pass type I membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    extracellular2

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane IEA--
    GO:0009986cell surface IDA19011627
    GO:0016021integral component of membrane IEA--

    Find genes that share ontologies with TIGIT           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TIGIT About    
    See pathways by source

    SuperPathContained pathways About
    1Cell adhesion molecules (CAMs)
    Cell adhesion molecules (CAMs)


    Find genes that share SuperPaths with TIGIT           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways




    1 Kegg Pathway  (Kegg details for TIGIT):
        Cell adhesion molecules (CAMs)

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for TIGIT
    Interactions:

        Search GeneGlobe Interaction Network for TIGIT

    STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

    4 Interacting proteins for TIGIT (Q495A11 ENSP000003731674) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PVRL3Q9NQS31, ENSP000004180704EBI-4314807,EBI-2826725 STRING: ENSP00000418070
    PVRL4Q96NY81, ENSP000003569914EBI-4314807,EBI-4314784 STRING: ENSP00000356991
    PVRENSP000004020604STRING: ENSP00000402060
    PVRL2ENSP000002524834STRING: ENSP00000252483
    About this table

    Gene Ontology (GO): 3 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0032695negative regulation of interleukin-12 production IMP19011627
    GO:0032733positive regulation of interleukin-10 production IMP19011627
    GO:0050868negative regulation of T cell activation IMP19011627

    Find genes that share ontologies with TIGIT           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
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    Browse Tocris compounds for TIGIT



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TIGIT gene: 
    NM_173799.3  

    Unigene Cluster for TIGIT:

    T cell immunoreceptor with Ig and ITIM domains
    Hs.421750  [show with all ESTs]
    Unigene Representative Sequence: NM_173799
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000461158 ENST00000481065 ENST00000486257 ENST00000485814 ENST00000484319
    ENST00000496848 ENST00000383671(uc003ebg.2)
    miRNA
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    hsa-miR-4264 hsa-miR-130a* hsa-miR-3120-3p hsa-miR-545 hsa-miR-23c hsa-miR-455-3p hsa-miR-33a* hsa-miR-942
    SwitchGear 3'UTR luciferase reporter plasmidTIGIT 3' UTR sequence
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    Additional mRNA sequence: 

    AK097192.1 BC101288.1 BC101289.1 BC101290.1 BC101291.1 BX640915.1 EU675310.1 

    4 DOTS entries:

    DT.100017515  DT.120919727  DT.120919733  DT.99939627 

    18 AceView cDNA sequences:

    AW768244 AW594641 AI365257 AA527065 AK097192 BX089103 BX089912 CA449645 
    NM_173799 BX640915 AI769887 AL833175 AW512550 AA353061 AA505489 AA527161 
    BQ377877 BG211784 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for TIGIT    About this scheme

    ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c · 6d · 6e
    SP1:                          -                       -                           
    SP2:                          -                       -                           
    SP3:                                                  -                           
    SP4:                          -                                                   
    SP5:                                                                              


    ECgene alternative splicing isoforms for TIGIT

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TIGIT expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    TIGIT Expression
    About this image

    TIGIT Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TIGIT Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.421750

    UniProtKB/Swiss-Prot: TIGIT_HUMAN, Q495A1
    Tissue specificity: 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)

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of human and mouse.

    Orthologs for TIGIT gene from Selected species (see all 6)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tigit1 , 5 T cell immunoreceptor with Ig and ITIM domains1, 5 75.31(n)1
    61.51(a)1
      16 (28.44 cM)5
    1000433141  NM_001146325.11  NP_001139797.11 
     436488615 


    ENSEMBL Gene Tree for TIGIT (if available)
    TreeFam Gene Tree for TIGIT (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TIGIT (see all 441)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs785237601,2
    C,F--114010850(+) GGAGTC/TTGGAG 1 -- us2k11Minor allele frequency- T:0.03WA 118
    rs770219651,2
    C--114010872(+) ACTCTA/TGACAA 1 -- us2k10--------
    rs794314901,2
    C--114010873(+) CTCTTC/GACAAA 1 -- us2k10--------
    rs1140107421,2
    F--114011001(+) GAACAC/TTTCAC 1 -- us2k11Minor allele frequency- T:0.02WA 118
    rs27334061,2
    C--114011017(-) AATTCA/TCTAGT 1 -- us2k18Minor allele frequency- T:0.06NA WA CSA EA 367
    rs26930531,2
    C--114011019(-) TTAATG/TCTCTA 1 -- us2k18Minor allele frequency- T:0.06NA WA CSA EA 367
    rs1807827641,2
    --114011035(+) CACAAC/TCCTAT 1 -- us2k10--------
    rs1161938901,2
    F--114011078(+) GGGAAA/GCTGAG 1 -- us2k11Minor allele frequency- G:0.01WA 118
    rs756498761,2
    C,F--114011226(+) AAAAAC/TAGAAA 1 -- us2k11Minor allele frequency- T:0.07WA 118
    rs1179735521,2
    C,F--114011338(+) AAACAC/TAGGCT 1 -- us2k11Minor allele frequency- T:0.02EA 120

    HapMap Linkage Disequilibrium report for TIGIT (113995760 - 114029135 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for TIGIT:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1507464CNV Deletion17803354
    esv2742710CNV Deletion23290073
    esv2043603CNV Deletion18987734
    esv2725786CNV Deletion23290073
    nsv822223CNV Loss20364138
    nsv441835CNV CNV18776908

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 612859    OMIM disorders: --


    Find genes that share disorders with TIGIT           About GenesLikeMe

    Genetic Association Database (GAD): TIGIT

    Export disorders for TIGIT gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TIGIT gene, integrated from 10 sources (see all 13):
    (articles sorted by number of sources associating them with TIGIT)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. (PubMed id 19011627)1, 2, 3 Yu X.... Grogan J.L. (Nat. Immunol. 2009)
    2. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering. (PubMed id 22421438)1, 2 Stengel K.F.... Grogan J.L. (Proc. Natl. Acad. Sci. U.S.A. 2012)
    3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    4. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. (PubMed id 23154388)1 Liu S....Fan Z. (Cell Death Differ. 2013)
    5. The TIGIT/CD226 axis regulates human T cell function. (PubMed id 22427644)1 Lozano E....Hafler D.A. (J. Immunol. 2012)
    6. Tim-3 pathway controls regulatory and effector T cell balance during hepatitis C virus infection. (PubMed id 22706088)1 Moorman J.P....Yao Z.Q. (J. Immunol. 2012)
    7. A secreted protein microarray platform for extracellular protein interaction discovery. (PubMed id 21982860)1 Ramani S.R....Gonzalez L.C. (Anal. Biochem. 2012)
    8. Vstm3 is a member of the CD28 family and an important modulator of T-cell function. (PubMed id 21416464)1 Levin S.D....Lewis K.E. (Eur. J. Immunol. 2011)
    9. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. (PubMed id 19815499)1 Stanietsky N....Mandelboim O. (Proc. Natl. Acad. Sci. U.S.A. 2009)
    10. A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. (PubMed id 19197944)1 Boles K.S....Colonna M. (Eur. J. Immunol. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 201633 HGNC: 26838 AceView: FLJ39873 Ensembl:ENSG00000181847 euGenes: HUgn201633
    ECgene: TIGIT Kegg: 201633 H-InvDB: TIGIT

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for TIGIT Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for TIGIT gene:
    Search GeneIP for patents involving TIGIT

    GeneCards and IP:
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