TVAL3_HUMAN
ID TVAL3_HUMAN Reviewed; 114 AA.
AC A0A0B4J271;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 04-MAR-2015, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=T cell receptor alpha variable 12-3 {ECO:0000303|Ref.2};
DE Flags: Precursor;
GN Name=TRAV12-3 {ECO:0000303|Ref.2};
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 GENOMIC DNA] (IMGT ALLELE TRAV12-3*01).
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
RP NOMENCLATURE.
RA Lefranc M.P., Lefranc G.;
RT "The T Cell Receptor FactsBook.";
RL (In) Lefranc M.P., Lefranc G. (eds.);
RL The T Cell Receptor FactsBook., pp.1-397, Academic Press, London. (2001).
RN [3]
RP REVIEW ON T CELL REPERTOIRE DIVERSITY.
RX PubMed=15040585; DOI=10.1038/nri1292;
RA Nikolich-Zugich J., Slifka M.K., Messaoudi I.;
RT "The many important facets of T-cell repertoire diversity.";
RL Nat. Rev. Immunol. 4:123-132(2004).
RN [4]
RP REVIEW ON T CELL RECEPTOR-CD3 COMPLEX ASSEMBLY, AND SUBCELLULAR LOCATION.
RX PubMed=20452950; DOI=10.1101/cshperspect.a005140;
RA Wucherpfennig K.W., Gagnon E., Call M.J., Huseby E.S., Call M.E.;
RT "Structural biology of the T-cell receptor: insights into receptor
RT assembly, ligand recognition, and initiation of signaling.";
RL Cold Spring Harb. Perspect. Biol. 2:A005140-A005140(2010).
RN [5]
RP REVIEW ON T CELL RECEPTOR SIGNALING.
RX PubMed=23524462; DOI=10.1038/nri3403;
RA Brownlie R.J., Zamoyska R.;
RT "T cell receptor signalling networks: branched, diversified and bounded.";
RL Nat. Rev. Immunol. 13:257-269(2013).
RN [6]
RP NOMENCLATURE.
RX PubMed=24600447; DOI=10.3389/fimmu.2014.00022;
RA Lefranc M.P.;
RT "Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise
RT of Immunoinformatics.";
RL Front. Immunol. 5:22-22(2014).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=25493333; DOI=10.1146/annurev-immunol-032414-112334;
RA Rossjohn J., Gras S., Miles J.J., Turner S.J., Godfrey D.I., McCluskey J.;
RT "T cell antigen receptor recognition of antigen-presenting molecules.";
RL Annu. Rev. Immunol. 33:169-200(2015).
RN [8] {ECO:0007744|PDB:4WWK}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 22-114, AND DISULFIDE BONDS.
RA Le Nours J., Praveena T., Pellicci D.G., Gherardin N.A., Lim R.T.,
RA Besra G., Keshipeddy S., Richardson S.K., Howell A.R., Gras S.,
RA Godfrey D.I., Rossjohn J., Uldrich A.P.;
RT "Crystal structure of human TCR Alpha Chain-TRAV12-3, Beta Chain-TRBV6-5,
RT Antigen-presenting molecule CD1d, and Beta-2-microglobulin.";
RL Submitted (NOV-2014) to the PDB data bank.
RN [9] {ECO:0007744|PDB:5HYJ}
RP X-RAY CRYSTALLOGRAPHY (3.06 ANGSTROMS) OF 24-113, AND DISULFIDE BONDS.
RX PubMed=27183386; DOI=10.1172/jci88165;
RA Stadinski B.D., Obst R., Huseby E.S.;
RT "A 'hotspot' for autoimmune T cells in type 1 diabetes.";
RL J. Clin. Invest. 126:2040-2042(2016).
RN [10] {ECO:0007744|PDB:5C07, ECO:0007744|PDB:5C08, ECO:0007744|PDB:5C09, ECO:0007744|PDB:5C0A, ECO:0007744|PDB:5C0B, ECO:0007744|PDB:5C0C}
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 24-113, AND DISULFIDE BONDS.
RX PubMed=27183389; DOI=10.1172/jci85679;
RA Cole D.K., Bulek A.M., Dolton G., Schauenberg A.J., Szomolay B.,
RA Rittase W., Trimby A., Jothikumar P., Fuller A., Skowera A., Rossjohn J.,
RA Zhu C., Miles J.J., Peakman M., Wooldridge L., Rizkallah P.J., Sewell A.K.;
RT "Hotspot autoimmune T cell receptor binding underlies pathogen and insulin
RT peptide cross-reactivity.";
RL J. Clin. Invest. 126:2191-2204(2016).
CC -!- FUNCTION: V region of the variable domain of T cell receptor (TR) alpha
CC chain that participates in the antigen recognition (PubMed:24600447).
CC Alpha-beta T cell receptors are antigen specific receptors which are
CC essential to the immune response and are present on the cell surface of
CC T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH)
CC complexes that are displayed by antigen presenting cells (APC), a
CC prerequisite for efficient T cell adaptive immunity against pathogens
CC (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates
CC TR-CD3 clustering on the cell surface and intracellular activation of
CC LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247
CC enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT,
CC which recruits numerous signaling molecules to form the LAT
CC signalosome. The LAT signalosome propagates signal branching to three
CC major signaling pathways, the calcium, the mitogen-activated protein
CC kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB)
CC pathways, leading to the mobilization of transcription factors that are
CC critical for gene expression and essential for T cell growth and
CC differentiation (PubMed:23524462). The T cell repertoire is generated
CC in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped
CC by intrathymic selection events to generate a peripheral T cell pool of
CC self-MH restricted, non-autoaggressive T cells. Post-thymic interaction
CC of alpha-beta TR with the pMH complexes shapes TR structural and
CC functional avidity (PubMed:15040585). {ECO:0000303|PubMed:15040585,
CC ECO:0000303|PubMed:23524462, ECO:0000303|PubMed:24600447,
CC ECO:0000303|PubMed:25493333}.
CC -!- SUBUNIT: Alpha-beta TR is a heterodimer composed of an alpha and beta
CC chain; disulfide-linked. The alpha-beta TR is associated with the
CC transmembrane signaling CD3 coreceptor proteins to form the TR-CD3 (TcR
CC or TCR). The assembly of alpha-beta TR heterodimers with CD3 occurs in
CC the endoplasmic reticulum where a single alpha-beta TR heterodimer
CC associates with one CD3D-CD3E heterodimer, one CD3G-CD3E heterodimer
CC and one CD247 homodimer forming a stable octomeric structure. CD3D-CD3E
CC and CD3G-CD3E heterodimers preferentially associate with TR alpha and
CC TR beta chains, respectively. The association of the CD247 homodimer is
CC the last step of TcR assembly in the endoplasmic reticulum and is
CC required for transport to the cell surface.
CC {ECO:0000303|PubMed:20452950}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000303|PubMed:20452950}.
CC -!- POLYMORPHISM: There are several alleles. The sequence shown is that of
CC IMGT allele TRAV12-3*01. {ECO:0000305}.
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DR EMBL; AC245505; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 4WWK; X-ray; 3.10 A; A=22-114.
DR PDB; 5C07; X-ray; 2.11 A; D/I=24-113.
DR PDB; 5C08; X-ray; 2.33 A; D/I=25-113.
DR PDB; 5C09; X-ray; 2.48 A; D/I=25-113.
DR PDB; 5C0A; X-ray; 2.46 A; D/I=25-113.
DR PDB; 5C0B; X-ray; 2.03 A; D/I=25-113.
DR PDB; 5C0C; X-ray; 1.97 A; D/I=24-113.
DR PDB; 5HYJ; X-ray; 3.06 A; D/I=24-113.
DR PDB; 6JXR; EM; 3.70 A; m=22-114.
DR PDBsum; 4WWK; -.
DR PDBsum; 5C07; -.
DR PDBsum; 5C08; -.
DR PDBsum; 5C09; -.
DR PDBsum; 5C0A; -.
DR PDBsum; 5C0B; -.
DR PDBsum; 5C0C; -.
DR PDBsum; 5HYJ; -.
DR PDBsum; 6JXR; -.
DR AlphaFoldDB; A0A0B4J271; -.
DR SMR; A0A0B4J271; -.
DR IMGT_GENE-DB; TRAV12-3; -.
DR GlyGen; A0A0B4J271; 1 site.
DR BioMuta; TRAV12-3; -.
DR PeptideAtlas; A0A0B4J271; -.
DR Ensembl; ENST00000390442.3; ENSP00000451822.1; ENSG00000211794.3.
DR GeneCards; TRAV12-3; -.
DR HGNC; HGNC:12107; TRAV12-3.
DR HPA; ENSG00000211794; Tissue enriched (lymphoid).
DR neXtProt; NX_A0A0B4J271; -.
DR OpenTargets; ENSG00000211794; -.
DR VEuPathDB; HostDB:ENSG00000211794; -.
DR GeneTree; ENSGT00940000153130; -.
DR HOGENOM; CLU_077975_8_3_1; -.
DR OMA; CAMSAQC; -.
DR PhylomeDB; A0A0B4J271; -.
DR ChiTaRS; TRAV12-3; human.
DR Pharos; A0A0B4J271; Tdark.
DR PRO; PR:A0A0B4J271; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; A0A0B4J271; protein.
DR Bgee; ENSG00000211794; Expressed in granulocyte and 100 other tissues.
DR GO; GO:0042101; C:T cell receptor complex; IEA:UniProtKB-KW.
DR GO; GO:0042605; F:peptide antigen binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Signal; T cell receptor.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..114
FT /note="T cell receptor alpha variable 12-3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000443266"
FT DOMAIN 24..>114
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..111
FT /evidence="ECO:0000269|PubMed:27183389,
FT ECO:0007744|PDB:4WWK, ECO:0007744|PDB:5C07,
FT ECO:0007744|PDB:5C08, ECO:0007744|PDB:5C09,
FT ECO:0007744|PDB:5C0A, ECO:0007744|PDB:5C0B,
FT ECO:0007744|PDB:5C0C, ECO:0007744|PDB:5HYJ"
FT NON_TER 114
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:5C07"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:5HYJ"
FT STRAND 66..80
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:5C0C"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:5C0C"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:5C0C"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:5C0C"
SQ SEQUENCE 114 AA; 13173 MW; 112CC3F3BC4DBE79 CRC64;
MMKSLRVLLV ILWLQLSWVW SQQKEVEQDP GPLSVPEGAI VSLNCTYSNS AFQYFMWYRQ
YSRKGPELLM YTYSSGNKED GRFTAQVDKS SKYISLFIRD SQPSDSATYL CAMS
