ID TIGIT_HUMAN Reviewed; 244 AA.
AC Q495A1; Q495A3; Q5JPD8; Q6MZS2; Q8N877;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 24-JAN-2024, entry version 147.
DE RecName: Full=T-cell immunoreceptor with Ig and ITIM domains;
DE AltName: Full=V-set and immunoglobulin domain-containing protein 9;
DE AltName: Full=V-set and transmembrane domain-containing protein 3;
DE Flags: Precursor;
GN Name=TIGIT; Synonyms=VSIG9, VSTM3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 21-244 (ISOFORM 2).
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH PVR; NECTIN2 AND NECTIN3, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=19011627; DOI=10.1038/ni.1674;
RA Yu X., Harden K., Gonzalez L.C., Francesco M., Chiang E., Irving B.,
RA Tom I., Ivelja S., Refino C.J., Clark H., Eaton D., Grogan J.L.;
RT "The surface protein TIGIT suppresses T cell activation by promoting the
RT generation of mature immunoregulatory dendritic cells.";
RL Nat. Immunol. 10:48-57(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 23-128 ALONE AND IN COMPLEX WITH
RP PVR, DISULFIDE BOND, SUBUNIT, AND MUTAGENESIS OF ILE-42.
RX PubMed=22421438; DOI=10.1073/pnas.1120606109;
RA Stengel K.F., Harden-Bowles K., Yu X., Rouge L., Yin J., Comps-Agrar L.,
RA Wiesmann C., Bazan J.F., Eaton D.L., Grogan J.L.;
RT "Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a
RT cell-cell adhesion and signaling mechanism that requires cis-trans receptor
RT clustering.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:5399-5404(2012).
CC -!- FUNCTION: Binds with high affinity to the poliovirus receptor (PVR)
CC which causes increased secretion of IL10 and decreased secretion of
CC IL12B and suppresses T-cell activation by promoting the generation of
CC mature immunoregulatory dendritic cells. {ECO:0000269|PubMed:19011627}.
CC -!- SUBUNIT: Homodimer in cis; binds with high affinity to PVR, forming a
CC heterotetrameric assembly of two TIGIT and two PVR molecules. Binds
CC with lower affinity to NECTIN2 and NECTIN3.
CC {ECO:0000269|PubMed:22421438}.
CC -!- INTERACTION:
CC Q495A1; Q15762: CD226; NbExp=4; IntAct=EBI-4314807, EBI-4314442;
CC Q495A1; P21145: MAL; NbExp=3; IntAct=EBI-4314807, EBI-3932027;
CC Q495A1; Q92692: NECTIN2; NbExp=6; IntAct=EBI-4314807, EBI-718419;
CC Q495A1; Q9NQS3: NECTIN3; NbExp=2; IntAct=EBI-4314807, EBI-2826725;
CC Q495A1; Q96NY8: NECTIN4; NbExp=2; IntAct=EBI-4314807, EBI-4314784;
CC Q495A1; Q9Y342: PLLP; NbExp=3; IntAct=EBI-4314807, EBI-3919291;
CC Q495A1; P15151: PVR; NbExp=2; IntAct=EBI-4314807, EBI-3919694;
CC Q495A1; Q495A1: TIGIT; NbExp=2; IntAct=EBI-4314807, EBI-4314807;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19011627};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:19011627}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q495A1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q495A1-2; Sequence=VSP_027634, VSP_027635;
CC -!- TISSUE SPECIFICITY: Expressed at low levels on peripheral memory and
CC regulatory CD4+ T-cells and NK cells and is up-regulated following
CC activation of these cells (at protein level).
CC {ECO:0000269|PubMed:19011627}.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAI46183.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK097192; BAC04973.1; -; mRNA.
DR EMBL; AL833175; CAI46183.1; ALT_INIT; mRNA.
DR EMBL; BX640915; CAE45956.1; -; mRNA.
DR EMBL; BC101288; AAI01289.1; -; mRNA.
DR EMBL; BC101289; AAI01290.1; -; mRNA.
DR EMBL; BC101290; AAI01291.1; -; mRNA.
DR EMBL; BC101291; AAI01292.1; -; mRNA.
DR CCDS; CCDS2980.1; -. [Q495A1-1]
DR RefSeq; NP_776160.2; NM_173799.3. [Q495A1-1]
DR PDB; 3Q0H; X-ray; 1.70 A; A/B=22-137.
DR PDB; 3RQ3; X-ray; 2.70 A; A/B=22-137.
DR PDB; 3UCR; X-ray; 2.63 A; A/B/C/D=23-128.
DR PDB; 3UDW; X-ray; 2.90 A; A/B=20-128.
DR PDB; 5V52; X-ray; 3.10 A; A/B=22-128.
DR PDB; 7VYT; X-ray; 1.53 A; A/T=23-129.
DR PDB; 8SZY; X-ray; 2.31 A; T/U=23-128.
DR PDBsum; 3Q0H; -.
DR PDBsum; 3RQ3; -.
DR PDBsum; 3UCR; -.
DR PDBsum; 3UDW; -.
DR PDBsum; 5V52; -.
DR PDBsum; 7VYT; -.
DR PDBsum; 8SZY; -.
DR AlphaFoldDB; Q495A1; -.
DR SMR; Q495A1; -.
DR BioGRID; 128399; 27.
DR IntAct; Q495A1; 7.
DR STRING; 9606.ENSP00000419085; -.
DR ChEMBL; CHEMBL4630878; -.
DR GlyCosmos; Q495A1; 2 sites, No reported glycans.
DR GlyGen; Q495A1; 2 sites.
DR iPTMnet; Q495A1; -.
DR PhosphoSitePlus; Q495A1; -.
DR BioMuta; TIGIT; -.
DR DMDM; 121943253; -.
DR jPOST; Q495A1; -.
DR MassIVE; Q495A1; -.
DR PaxDb; 9606-ENSP00000419085; -.
DR PeptideAtlas; Q495A1; -.
DR ProteomicsDB; 61948; -. [Q495A1-1]
DR ABCD; Q495A1; 190 sequenced antibodies.
DR Antibodypedia; 53759; 560 antibodies from 30 providers.
DR DNASU; 201633; -.
DR Ensembl; ENST00000383671.8; ENSP00000373167.3; ENSG00000181847.12. [Q495A1-1]
DR Ensembl; ENST00000486257.5; ENSP00000419085.1; ENSG00000181847.12. [Q495A1-1]
DR GeneID; 201633; -.
DR KEGG; hsa:201633; -.
DR MANE-Select; ENST00000383671.8; ENSP00000373167.3; NM_173799.4; NP_776160.2.
DR UCSC; uc003ebg.3; human. [Q495A1-1]
DR AGR; HGNC:26838; -.
DR CTD; 201633; -.
DR DisGeNET; 201633; -.
DR GeneCards; TIGIT; -.
DR HGNC; HGNC:26838; TIGIT.
DR HPA; ENSG00000181847; Tissue enriched (lymphoid).
DR MIM; 612859; gene.
DR neXtProt; NX_Q495A1; -.
DR OpenTargets; ENSG00000181847; -.
DR PharmGKB; PA164726482; -.
DR VEuPathDB; HostDB:ENSG00000181847; -.
DR eggNOG; ENOG502SQW2; Eukaryota.
DR GeneTree; ENSGT00390000012671; -.
DR HOGENOM; CLU_073090_0_0_1; -.
DR InParanoid; Q495A1; -.
DR OMA; HIYPAFR; -.
DR OrthoDB; 5323366at2759; -.
DR PhylomeDB; Q495A1; -.
DR TreeFam; TF338423; -.
DR PathwayCommons; Q495A1; -.
DR SignaLink; Q495A1; -.
DR SIGNOR; Q495A1; -.
DR BioGRID-ORCS; 201633; 7 hits in 1146 CRISPR screens.
DR ChiTaRS; TIGIT; human.
DR EvolutionaryTrace; Q495A1; -.
DR GenomeRNAi; 201633; -.
DR Pharos; Q495A1; Tbio.
DR PRO; PR:Q495A1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q495A1; Protein.
DR Bgee; ENSG00000181847; Expressed in granulocyte and 106 other cell types or tissues.
DR ExpressionAtlas; Q495A1; baseline and differential.
DR Genevisible; Q495A1; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR042948; TIGIT.
DR PANTHER; PTHR47734:SF1; T-CELL IMMUNORECEPTOR WITH IG AND ITIM DOMAINS; 1.
DR PANTHER; PTHR47734; T-CELL IMMUNORECEPTOR WITH IG AND ITIM DOMAINS PROTEIN, TIGIT; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..244
FT /note="T-cell immunoreceptor with Ig and ITIM domains"
FT /id="PRO_0000299405"
FT TOPO_DOM 22..141
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..124
FT /note="Ig-like V-type"
FT REGION 32..42
FT /note="Homodimerization"
FT MOTIF 229..234
FT /note="ITIM motif"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:22421438"
FT VAR_SEQ 167..170
FT /note="KKAL -> FVCF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_027634"
FT VAR_SEQ 171..244
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_027635"
FT VARIANT 33
FT /note="I -> V (in dbSNP:rs13098836)"
FT /id="VAR_056079"
FT MUTAGEN 42
FT /note="I->A: Abrogates interaction with PVR, cell
FT clustering and PVR signaling."
FT /evidence="ECO:0000269|PubMed:22421438"
FT MUTAGEN 42
FT /note="I->D: Abrogates interaction with PVR, cell
FT clustering and PVR signaling."
FT /evidence="ECO:0000269|PubMed:22421438"
FT CONFLICT 103
FT /note="T -> A (in Ref. 3; AAI01289)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="T -> A (in Ref. 1; BAC04973)"
FT /evidence="ECO:0000305"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:7VYT"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:7VYT"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:7VYT"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:7VYT"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 104..113
FT /evidence="ECO:0007829|PDB:7VYT"
FT STRAND 116..127
FT /evidence="ECO:0007829|PDB:7VYT"
SQ SEQUENCE 244 AA; 26319 MW; B890AF73F618C851 CRC64;
MRWCLLLIWA QGLRQAPLAS GMMTGTIETT GNISAEKGGS IILQCHLSST TAQVTQVNWE
QQDQLLAICN ADLGWHISPS FKDRVAPGPG LGLTLQSLTV NDTGEYFCIY HTYPDGTYTG
RIFLEVLESS VAEHGARFQI PLLGAMAATL VVICTAVIVV VALTRKKKAL RIHSVEGDLR
RKSAGQEEWS PSAPSPPGSC VQAEAAPAGL CGEQRGEDCA ELHDYFNVLS YRSLGNCSFF
TETG
//
