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 16-JAN-2019, entry version 27. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE RP 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., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA 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., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., 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. RL (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 RP 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 RT 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 RT Rise 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., RA McCluskey J.; RT "T cell antigen receptor recognition of antigen-presenting RT molecules."; RL Annu. Rev. Immunol. 33:169-200(2015). RN [8] {ECO:0000244|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- RT TRBV6-5, Antigen-presenting molecule CD1d, and Beta-2-microglobulin."; RL Submitted (NOV-2014) to the PDB data bank. RN [9] {ECO:0000244|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:0000244|PDB:5C07, ECO:0000244|PDB:5C08, ECO:0000244|PDB:5C09, ECO:0000244|PDB:5C0A, ECO:0000244|PDB:5C0B, ECO:0000244|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., RA Rossjohn J., Zhu C., Miles J.J., Peakman M., Wooldridge L., RA Rizkallah P.J., Sewell A.K.; RT "Hotspot autoimmune T cell receptor binding underlies pathogen and RT insulin peptide cross-reactivity."; RL J. Clin. Invest. 126:2191-2204(2016). CC -!- FUNCTION: V region of the variable domain of T cell receptor (TR) CC alpha chain that participates in the antigen recognition CC (PubMed:24600447). Alpha-beta T cell receptors are antigen CC specific receptors which are essential to the immune response and CC are present on the cell surface of T lymphocytes. Recognize CC peptide-major histocompatibility (MH) (pMH) complexes that are CC displayed by antigen presenting cells (APC), a prerequisite for CC efficient T cell adaptive immunity against pathogens CC (PubMed:25493333). Binding of alpha-beta TR to pMH complex CC initiates TR-CD3 clustering on the cell surface and intracellular CC activation of LCK that phosphorylates the ITAM motifs of CD3G, CC CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn CC ZAP70 phosphorylates LAT, which recruits numerous signaling CC molecules to form the LAT signalosome. The LAT signalosome CC propagates signal branching to three major signaling pathways, the CC calcium, the mitogen-activated protein kinase (MAPK) kinase and CC the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the CC mobilization of transcription factors that are critical for gene CC expression and essential for T cell growth and differentiation CC (PubMed:23524462). The T cell repertoire is generated in the CC thymus, by V-(D)-J rearrangement. This repertoire is then shaped CC by intrathymic selection events to generate a peripheral T cell CC pool of self-MH restricted, non-autoaggressive T cells. Post- CC thymic interaction of alpha-beta TR with the pMH complexes shapes CC TR structural and functional avidity (PubMed:15040585). CC {ECO:0000303|PubMed:15040585, ECO:0000303|PubMed:23524462, CC ECO:0000303|PubMed:24600447, ECO:0000303|PubMed:25493333}. CC -!- SUBUNIT: Alpha-beta TR is a heterodimer composed of an alpha and CC beta chain; disulfide-linked. The alpha-beta TR is associated with CC the transmembrane signaling CD3 coreceptor proteins to form the CC TR-CD3 (TcR or TCR). The assembly of alpha-beta TR heterodimers CC with CD3 occurs in the endoplasmic reticulum where a single alpha- CC beta TR heterodimer associates with one CD3D-CD3E heterodimer, one CC CD3G-CD3E heterodimer and one CD247 homodimer forming a stable CC octomeric structure. CD3D-CD3E and CD3G-CD3E heterodimers CC preferentially associate with TR alpha and TR beta chains, CC respectively. The association of the CD247 homodimer is the last CC step of TcR assembly in the endoplasmic reticulum and is required CC for transport to the cell surface. {ECO:0000303|PubMed:20452950}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000303|PubMed:20452950}. CC -!- POLYMORPHISM: There are several alleles. The sequence shown is CC that of IMGT allele TRAV12-3*01. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 PDBsum; 4WWK; -. DR PDBsum; 5C07; -. DR PDBsum; 5C08; -. DR PDBsum; 5C09; -. DR PDBsum; 5C0A; -. DR PDBsum; 5C0B; -. DR PDBsum; 5C0C; -. DR PDBsum; 5HYJ; -. DR SMR; A0A0B4J271; -. DR IMGT_GENE-DB; TRAV12-3; -. DR BioMuta; TRAV12-3; -. DR PeptideAtlas; A0A0B4J271; -. DR Ensembl; ENST00000390442; ENSP00000451822; ENSG00000211794. DR EuPathDB; HostDB:ENSG00000211794.3; -. DR GeneCards; TRAV12-3; -. DR HGNC; HGNC:12107; TRAV12-3. DR neXtProt; NX_A0A0B4J271; -. DR OpenTargets; ENSG00000211794; -. DR GeneTree; ENSGT00940000153130; -. DR OMA; CAMSAQC; -. DR ChiTaRS; TRAV12-3; human. DR PRO; PR:A0A0B4J271; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211794; Expressed in 65 organ(s), highest expression level in leukocyte. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. 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; Complete proteome; KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; KW Membrane; Polymorphism; Receptor; Reference proteome; Signal. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 114 T cell receptor alpha variable 12-3. FT {ECO:0000255}. FT /FTId=PRO_0000443266. FT DOMAIN 24 >114 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT CARBOHYD 44 44 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 45 111 {ECO:0000244|PDB:4WWK, FT ECO:0000244|PDB:5C07, FT ECO:0000244|PDB:5C08, FT ECO:0000244|PDB:5C09, FT ECO:0000244|PDB:5C0A, FT ECO:0000244|PDB:5C0B, FT ECO:0000244|PDB:5C0C, FT ECO:0000244|PDB:5HYJ, FT ECO:0000269|PubMed:27183389}. FT NON_TER 114 114 FT STRAND 26 28 {ECO:0000244|PDB:5C07}. FT STRAND 33 36 {ECO:0000244|PDB:5C0C}. FT STRAND 41 47 {ECO:0000244|PDB:5C0C}. FT STRAND 54 60 {ECO:0000244|PDB:5C0C}. FT STRAND 62 64 {ECO:0000244|PDB:5HYJ}. FT STRAND 66 80 {ECO:0000244|PDB:5C0C}. FT STRAND 83 88 {ECO:0000244|PDB:5C0C}. FT TURN 89 92 {ECO:0000244|PDB:5C0C}. FT STRAND 93 100 {ECO:0000244|PDB:5C0C}. FT HELIX 103 105 {ECO:0000244|PDB:5C0C}. FT STRAND 107 113 {ECO:0000244|PDB:5C0C}. SQ SEQUENCE 114 AA; 13173 MW; 112CC3F3BC4DBE79 CRC64; MMKSLRVLLV ILWLQLSWVW SQQKEVEQDP GPLSVPEGAI VSLNCTYSNS AFQYFMWYRQ YSRKGPELLM YTYSSGNKED GRFTAQVDKS SKYISLFIRD SQPSDSATYL CAMS //