TRAR1_HUMAN
ID TRAR1_HUMAN Reviewed; 268 AA.
AC P0DSE1;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 25-MAY-2022, entry version 14.
DE RecName: Full=M1-specific T cell receptor alpha chain {ECO:0000305|PubMed:29997621};
DE AltName: Full=TR alpha chain TRAV27*01J42*01C*01 {ECO:0000303|PubMed:8550091, ECO:0000305|PubMed:29997621};
DE Flags: Precursor;
GN Name=TRA {ECO:0000312|HGNC:HGNC:12027};
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 [MRNA] OF 1-128, CDR3 DOMAIN, AND FUNCTION.
RX PubMed=1833769; DOI=10.1073/pnas.88.20.8987;
RA Moss P.A., Moots R.J., Rosenberg W.M., Rowland-Jones S.J., Bodmer H.C.,
RA McMichael A.J., Bell J.I.;
RT "Extensive conservation of alpha and beta chains of the human T-cell
RT antigen receptor recognizing HLA-A2 and influenza A matrix peptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:8987-8990(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-128, CDR3 DOMAIN, FUNCTION, AND VARIANT
RP ALA-110.
RX PubMed=7807026; DOI=10.1084/jem.181.1.79;
RA Lehner P.J., Wang E.C., Moss P.A., Williams S., Platt K., Friedman S.M.,
RA Bell J.I., Borysiewicz L.K.;
RT "Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza
RT A is dominated by T cells bearing the V beta 17 gene segment.";
RL J. Exp. Med. 181:79-91(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-128, CDR3 DOMAIN, FUNCTION, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=29997621; DOI=10.3389/fimmu.2018.01453;
RA Sant S., Grzelak L., Wang Z., Pizzolla A., Koutsakos M., Crowe J.,
RA Loudovaris T., Mannering S.I., Westall G.P., Wakim L.M., Rossjohn J.,
RA Gras S., Richards M., Xu J., Thomas P.G., Loh L., Nguyen T.H.O.,
RA Kedzierska K.;
RT "Single-Cell Approach to Influenza-Specific CD8+ T Cell Receptor
RT Repertoires Across Different Age Groups, Tissues, and Following Influenza
RT Virus Infection.";
RL Front. Immunol. 9:1453-1453(2018).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 129-268 (IMGT ALLELE TRAC*01).
RX PubMed=3875483; DOI=10.1002/j.1460-2075.1985.tb03803.x;
RA Rabbitts T.H., Lefranc M.P., Stinson M.A., Sims J.E., Schroder J.,
RA Steinmetz M., Spurr N.L., Solomon E., Goodfellow P.N.;
RT "The chromosomal location of T-cell receptor genes and a T cell rearranging
RT gene: possible correlation with specific translocations in human T cell
RT leukaemia.";
RL EMBO J. 4:1461-1465(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRAV27*03 AND
RP IMGT ALLELE TRAJ42*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 [6]
RP NOMENCLATURE.
RX PubMed=8550091; DOI=10.1007/bf00172175;
RG WHO-IUIS Nomenclature Sub-Committee on TCR Designation.;
RT "Nomenclature for T-cell receptor (TCR) gene segments of the immune
RT system.";
RL Immunogenetics 42:451-453(1995).
RN [7]
RP CDR1 AND CDR2 DOMAINS.
RX PubMed=11096259; DOI=10.1159/000019140;
RA Folch G., Scaviner D., Contet V., Lefranc M.P.;
RT "Protein displays of the human T cell receptor alpha, beta, gamma and delta
RT variable and joining regions.";
RL Exp. Clin. Immunogenet. 17:205-215(2000).
RN [8]
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 [9]
RP NOMENCLATURE.
RX PubMed=19568742; DOI=10.1007/s00251-009-0383-x;
RA Yassai M.B., Naumov Y.N., Naumova E.N., Gorski J.;
RT "A clonotype nomenclature for T cell receptors.";
RL Immunogenetics 61:493-502(2009).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 19-219, INTERACTION WITH
RP PEPTIDE-HLA-A*02-B2M, FUNCTION, DOMAIN, AND VARIANT ALA-110.
RX PubMed=12796775; DOI=10.1038/ni942;
RA Stewart-Jones G.B.E., McMichael A.J., Bell J.I., Stuart D.I., Jones E.Y.;
RT "A structural basis for immunodominant human T cell receptor recognition.";
RL Nat. Immunol. 4:657-663(2003).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 20-217, INTERACTION WITH
RP PEPTIDE-HLA-A*02-B2M, FUNCTION, MUTAGENESIS OF SER-48; SER-49 AND GLN-51,
RP DOMAIN, AND VARIANT ALA-110.
RX PubMed=18275829; DOI=10.1016/j.immuni.2007.12.018;
RA Ishizuka J., Stewart-Jones G.B., van der Merwe A., Bell J.I.,
RA McMichael A.J., Jones E.Y.;
RT "The structural dynamics and energetics of an immunodominant T cell
RT receptor are programmed by its Vbeta domain.";
RL Immunity 28:171-182(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 20-217, FUNCTION, INTERACTION
RP WITH PEPTIDE-HLA-A*02-B2M, DISULFIDE BOND, TISSUE SPECIFICITY, DOMAIN, AND
RP VARIANT ALA-110.
RX PubMed=27036003; DOI=10.1073/pnas.1603106113;
RA Valkenburg S.A., Josephs T.M., Clemens E.B., Grant E.J., Nguyen T.H.,
RA Wang G.C., Price D.A., Miller A., Tong S.Y., Thomas P.G., Doherty P.C.,
RA Rossjohn J., Gras S., Kedzierska K.;
RT "Molecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity
RT against influenza viruses.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:4440-4445(2016).
CC -!- FUNCTION: The alpha chain of TRAV27*01J42*01C*01/TRBV19*01J2S7*01C*02
CC alpha-beta T cell receptor (TR) clonotype that is specific for HLA-
CC A*02:01-restricted M/matrix protein 1 immunodominant epitope GILGFVFTL
CC of influenza A virus (IAV). Classified as a public TR clonotype, it is
CC preferentially selected in effector memory CD8-positive T cells among
CC multiple HLA-A*02:01 carriers and confers long-lived immunity against
CC IAV infection. Can cross-recognize sporadically emerging IAV variants
CC by molecular mimicry, inducing immunity toward different influenza
CC strains (PubMed:1833769, PubMed:7807026, PubMed:29997621,
CC PubMed:27036003, PubMed:12796775, PubMed:18275829). Antigen recognition
CC initiates TR-CD3 clustering on the cell surface and intracellular
CC activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D,
CC CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70
CC phosphorylates LAT, which recruits numerous signaling molecules to form
CC the LAT signalosome. The LAT signalosome propagates signal branching to
CC three major signaling pathways, the calcium, the mitogen-activated
CC protein 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 differentiation
CC into effector/memory T cells (By similarity).
CC {ECO:0000250|UniProtKB:P01848, ECO:0000269|PubMed:12796775,
CC ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:1833769,
CC ECO:0000269|PubMed:27036003, ECO:0000269|PubMed:29997621,
CC ECO:0000269|PubMed:7807026}.
CC -!- SUBUNIT: Disulfide-linked heterodimer with TRBV19*01J2S7*01C*02 beta
CC chain. The TR primarily interacts via its CDR3-beta domain with
CC M/matrix protein 1-derived peptide (GILGFVFTL) displayed by HLA-A*02.01
CC in a 'peg-notch' recognition mode (PubMed:27036003, PubMed:12796775,
CC PubMed:18275829). The alpha-beta TR associates with the transmembrane
CC signaling CD3 coreceptor proteins to form the TR-CD3 (TCR). The
CC assembly of alpha-beta TR heterodimers with CD3 occurs in the
CC 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 (via TM domain), respectively. The association of the
CC CD247 homodimer is the last step of TCR assembly in the endoplasmic
CC reticulum and is required for transport to the cell surface (By
CC similarity). {ECO:0000250|UniProtKB:P01848,
CC ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:18275829,
CC ECO:0000269|PubMed:27036003}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29997621}.
CC -!- TISSUE SPECIFICITY: Expressed in M/matrix protein 1-specific effector
CC and memory CD8-positive T cells readily detectable in the peripheral
CC blood, secondary lymphoid organs and lung (primary site of infection)
CC of IAV infected individuals. {ECO:0000269|PubMed:27036003,
CC ECO:0000269|PubMed:29997621}.
CC -!- DOMAIN: The complementarity-determining region CDR1 confers specificity
CC to the peptide antigen. Assumes a loop structure that makes contact
CC with HLA-A*02.01 and contributes to the stability of the TR through
CC interaction with CDR3-beta loop. {ECO:0000269|PubMed:12796775,
CC ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:27036003,
CC ECO:0000305|PubMed:11096259}.
CC -!- DOMAIN: The complementarity-determining region CDR2 confers specificity
CC to the peptide antigen. Assumes a loop structure that recognizes the
CC peptide-HLA-A*02-B2M complex. {ECO:0000269|PubMed:12796775,
CC ECO:0000269|PubMed:27036003, ECO:0000305|PubMed:11096259}.
CC -!- DOMAIN: The complementarity-determining region CDR3 confers specificity
CC to the peptide antigen. Assumes a loop structure that recognizes the
CC peptide-HLA-A*02-B2M complex. {ECO:0000269|PubMed:12796775,
CC ECO:0000269|PubMed:1833769, ECO:0000269|PubMed:27036003,
CC ECO:0000269|PubMed:29997621, ECO:0000269|PubMed:7807026}.
CC -!- DOMAIN: The connecting peptide (CP) domain contributes to the TR-CD3
CC assembly and signal transduction. {ECO:0000250|UniProtKB:P01848}.
CC -!- DOMAIN: The TM domain mediates the interaction with the CD3 subunits.
CC {ECO:0000250|UniProtKB:P01848}.
CC -!- MISCELLANEOUS: The JM22 clone described as a variant of the public
CC clonotype differs by one amino acid in the CDR3-alpha domain.
CC {ECO:0000305|PubMed:12796775, ECO:0000305|PubMed:18275829,
CC ECO:0000305|PubMed:27036003, ECO:0000305|PubMed:7807026}.
CC -!- CAUTION: This sequence is an example of a full-length TR alpha chain.
CC M/matrix protein 1-specific TRAV27*01J42*01C*01 TR alpha chain is
CC generated by somatic recombination of variable TRAV27 (AC A0A087WT01)
CC and joining TRAJ42 (AC A0A075B6Y9) gene segments spliced to constant
CC TRAC (AC P01848) gene segment. {ECO:0000269|PubMed:1833769,
CC ECO:0000269|PubMed:27036003, ECO:0000269|PubMed:29997621}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA26435.1; Type=Miscellaneous discrepancy; Note=Chimeric mRNA corresponding to regions V, J and C of T cell receptor (TR) alpha chain.; Evidence={ECO:0000305};
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DR EMBL; AAB20033; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X02592; CAA26435.1; ALT_SEQ; mRNA.
DR EMBL; AC245470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC243965; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 1OGA; X-ray; 1.40 A; -.
DR PDB; 2VLJ; X-ray; 2.40 A; -.
DR PDB; 2VLK; X-ray; 2.50 A; -.
DR PDB; 2VLR; X-ray; 2.30 A; -.
DR PDB; 5HHM; X-ray; 2.50 A; -.
DR PDB; 5HHO; X-ray; 2.95 A; -.
DR PDBsum; 1OGA; -.
DR PDBsum; 2VLJ; -.
DR PDBsum; 2VLK; -.
DR PDBsum; 2VLR; -.
DR PDBsum; 5HHM; -.
DR PDBsum; 5HHO; -.
DR AlphaFoldDB; P0DSE1; -.
DR SMR; P0DSE1; -.
DR PeptideAtlas; P0DSE1; -.
DR GeneCards; TRA; -.
DR HGNC; HGNC:12027; TRA.
DR MalaCards; TRA; -.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR ChiTaRS; TRA; human.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042101; C:T cell receptor complex; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IDA:UniProtKB.
DR GO; GO:0002286; P:T cell activation involved in immune response; IDA:UniProtKB.
DR CDD; cd07688; IgC_TCR_alpha; 1.
DR Gene3D; 2.60.40.10; -; 2.
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; IPR015370; TCR_alpha_C.
DR Pfam; PF09291; DUF1968; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Membrane; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..268
FT /note="M1-specific T cell receptor alpha chain"
FT /id="PRO_0000447044"
FT TRANSMEM 244..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..107
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 147..235
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 20..109
FT /note="T cell receptor alpha variable 27"
FT /evidence="ECO:0000305|PubMed:12508121"
FT REGION 45..49
FT /note="CDR1"
FT /evidence="ECO:0000269|PubMed:12796775,
FT ECO:0000269|PubMed:27036003, ECO:0000305|PubMed:11096259"
FT REGION 67..69
FT /note="CDR2"
FT /evidence="ECO:0000269|PubMed:12796775,
FT ECO:0000269|PubMed:27036003, ECO:0000305|PubMed:11096259"
FT REGION 107..118
FT /note="CDR3"
FT /evidence="ECO:0000269|PubMed:12796775,
FT ECO:0000269|PubMed:1833769, ECO:0000269|PubMed:27036003,
FT ECO:0000269|PubMed:29997621, ECO:0000269|PubMed:7807026"
FT REGION 110..128
FT /note="T cell receptor alpha joining 42"
FT /evidence="ECO:0000305|PubMed:12508121"
FT REGION 129..268
FT /note="T cell receptor alpha constant"
FT /evidence="ECO:0000305|PubMed:3875483"
FT REGION 222..243
FT /note="Connecting peptide"
FT /evidence="ECO:0000250|UniProtKB:P01848"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P01848,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P01848,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 41..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:27036003"
FT DISULFID 150..200
FT /evidence="ECO:0000250|UniProtKB:P01848"
FT DISULFID 222
FT /note="Interchain (with C-262 in TRBC2)"
FT /evidence="ECO:0000250|UniProtKB:P01848"
FT VARIANT 110
FT /note="G -> A"
FT /evidence="ECO:0000305|PubMed:12796775,
FT ECO:0000305|PubMed:18275829, ECO:0000305|PubMed:27036003,
FT ECO:0000305|PubMed:7807026"
FT /id="VAR_081650"
FT MUTAGEN 48
FT /note="S->A: Decreases the affinity for M/matrix protein 1
FT peptide antigen."
FT /evidence="ECO:0000269|PubMed:18275829"
FT MUTAGEN 49
FT /note="S->A: Decreases the affinity for M/matrix protein 1
FT peptide antigen."
FT /evidence="ECO:0000269|PubMed:18275829"
FT MUTAGEN 51
FT /note="Q->A: Decreases the affinity for M/matrix protein 1
FT peptide antigen."
FT /evidence="ECO:0000269|PubMed:18275829"
FT CONFLICT 99
FT /note="P -> T (in Ref. 5; AC245470)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 268 AA; 29608 MW; D627271D6D7D2EB3 CRC64;
MVLKFSVSIL WIQLAWVSTQ LLEQSPQFLS IQEGENLTVY CNSSSVFSSL QWYRQEPGEG
PVLLVTVVTG GEVKKLKRLT FQFGDARKDS SLHITAAQPG DTGLYLCAGG GSQGNLIFGK
GTKLSVKPIQ NPDPAVYQLR DSKSSDKSVC LFTDFDSQTN VSQSKDSDVY ITDKTVLDMR
SMDFKSNSAV AWSNKSDFAC ANAFNNSIIP EDTFFPSPES SCDVKLVEKS FETDTNLNFQ
NLSVIGFRIL LLKVAGFNLL MTLRLWSS
