ID TVA21_HUMAN Reviewed; 112 AA. AC A0A0B4J279; 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 21 {ECO:0000303|Ref.2}; DE Flags: Precursor; GN Name=TRAV21 {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 TRAV21*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:2BNQ, ECO:0000244|PDB:2BNR, ECO:0000244|PDB:2BNU} RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 21-112, AND DISULFIDE BONDS. RX PubMed=15837811; DOI=10.1084/jem.20042323; RA Chen J.-L., Stewart-Jones G., Bossi G., Lissin N.M., Wooldridge L., RA Choi E.M.L., Held G., Dunbar P.R., Esnouf R.M., Sami M., Boulter J.M., RA Rizkallah P., Renner C., Sewell A., van der Merwe P.A., Jakobsen B.K., RA Griffiths G., Jones E.Y., Cerundolo V.; RT "Structural and kinetic basis for heightened immunogenicity of T cell RT vaccines."; RL J. Exp. Med. 201:1243-1255(2005). RN [9] {ECO:0000244|PDB:4WW1} RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 20-110, AND DISULFIDE BONDS. RA Le Nours J., Praveena T., Pellicci D.P., Lim R.T., Besra G., RA Howell A.R., Godfrey D.I., Rossjohn J., Uldrich A.P.; RT "Crystal structure of human TCR Alpha Chain-TRAV21-TRAJ8 and Beta RT Chain-TRBV7-8."; RL Submitted (NOV-2014) to the PDB data bank. RN [10] {ECO:0000244|PDB:4WW2} RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 20-110, AND DISULFIDE BONDS. RA Le Nours J., Praveena T., Pellicci D., 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-TRAV21-TRAJ8, Beta Chain- RT TRBV7-8, Antigen-presenting glycoprotein CD1d, and Beta-2- RT microglobulin."; RL Submitted (NOV-2014) to the PDB data bank. RN [11] {ECO:0000244|PDB:5EU6} RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 20-111, AND DISULFIDE BONDS. RX PubMed=26917722; DOI=10.1074/jbc.M115.707414; RA Bianchi V., Bulek A., Fuller A., Lloyd A., Attaf M., Rizkallah P.J., RA Dolton G., Sewell A.K., Cole D.K.; RT "A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor RT (TCR) Targeting of a Human Melanoma Antigen."; RL J. Biol. Chem. 291:8951-8959(2016). RN [12] {ECO:0000244|PDB:5BRZ, ECO:0000244|PDB:5BS0} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 21-112, AND DISULFIDE BONDS. RX PubMed=26758806; DOI=10.1038/srep18851; RA Raman M.C., Rizkallah P.J., Simmons R., Donnellan Z., Dukes J., RA Bossi G., Le Provost G.S., Todorov P., Baston E., Hickman E., RA Mahon T., Hassan N., Vuidepot A., Sami M., Cole D.K., Jakobsen B.K.; RT "Direct molecular mimicry enables off-target cardiovascular toxicity RT by an enhanced affinity TCR designed for cancer immunotherapy."; RL Sci. Rep. 6:18851-18851(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 TRAV21*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; 2BNQ; X-ray; 1.70 A; D=21-112. DR PDB; 2BNR; X-ray; 1.90 A; D=21-112. DR PDB; 2BNU; X-ray; 1.40 A; A=21-112. DR PDB; 4WW1; X-ray; 1.38 A; A=20-110. DR PDB; 4WW2; X-ray; 2.48 A; A=20-110. DR PDB; 5BRZ; X-ray; 2.62 A; D=21-112. DR PDB; 5BS0; X-ray; 2.40 A; D=21-112. DR PDB; 5EU6; X-ray; 2.02 A; D=20-111. DR PDBsum; 2BNQ; -. DR PDBsum; 2BNR; -. DR PDBsum; 2BNU; -. DR PDBsum; 4WW1; -. DR PDBsum; 4WW2; -. DR PDBsum; 5BRZ; -. DR PDBsum; 5BS0; -. DR PDBsum; 5EU6; -. DR ProteinModelPortal; A0A0B4J279; -. DR SMR; A0A0B4J279; -. DR IMGT_GENE-DB; TRAV21; -. DR BioMuta; TRAV21; -. DR PeptideAtlas; A0A0B4J279; -. DR Ensembl; ENST00000390449; ENSP00000452526; ENSG00000211801. DR EuPathDB; HostDB:ENSG00000211801.3; -. DR GeneCards; TRAV21; -. DR HGNC; HGNC:12118; TRAV21. DR neXtProt; NX_A0A0B4J279; -. DR OpenTargets; ENSG00000211801; -. DR GeneTree; ENSGT00940000163708; -. DR OMA; WVSSKQE; -. DR PRO; PR:A0A0B4J279; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211801; Expressed in 76 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 19 {ECO:0000255}. FT CHAIN 20 112 T cell receptor alpha variable 21. FT {ECO:0000255}. FT /FTId=PRO_5002107034. FT DOMAIN 21 >112 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT CARBOHYD 41 41 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 82 82 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 42 109 {ECO:0000244|PDB:2BNQ, FT ECO:0000244|PDB:2BNR, FT ECO:0000244|PDB:2BNU, FT ECO:0000244|PDB:4WW1, FT ECO:0000244|PDB:4WW2, FT ECO:0000244|PDB:5BRZ, FT ECO:0000244|PDB:5BS0, FT ECO:0000244|PDB:5EU6, FT ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:15837811, FT ECO:0000269|PubMed:26758806, FT ECO:0000269|PubMed:26917722}. FT NON_TER 112 112 FT STRAND 23 26 {ECO:0000244|PDB:4WW1}. FT STRAND 28 33 {ECO:0000244|PDB:4WW1}. FT STRAND 38 45 {ECO:0000244|PDB:4WW1}. FT STRAND 49 57 {ECO:0000244|PDB:4WW1}. FT STRAND 59 61 {ECO:0000244|PDB:4WW2}. FT STRAND 64 72 {ECO:0000244|PDB:4WW1}. FT STRAND 74 78 {ECO:0000244|PDB:4WW1}. FT STRAND 81 86 {ECO:0000244|PDB:4WW1}. FT TURN 87 90 {ECO:0000244|PDB:4WW1}. FT STRAND 91 96 {ECO:0000244|PDB:4WW1}. FT HELIX 101 103 {ECO:0000244|PDB:4WW1}. FT STRAND 105 110 {ECO:0000244|PDB:4WW1}. SQ SEQUENCE 112 AA; 12289 MW; 5D003A16FD4B7021 CRC64; METLLGLLIL WLQLQWVSSK QEVTQIPAAL SVPEGENLVL NCSFTDSAIY NLQWFRQDPG KGLTSLLLIQ SSQREQTSGR LNASLDKSSG RSTLYIAASQ PGDSATYLCA VR //