TRAR2_HUMAN
ID TRAR2_HUMAN Reviewed; 275 AA.
AC P0DTU3;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 1.
DT 25-MAY-2022, entry version 8.
DE RecName: Full=T cell receptor alpha chain MC.7.G5;
DE AltName: Full=MC.7.G5 TRA;
DE AltName: Full=TR alpha chain TRAV38-2DV8*01J31*01C*01;
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], REGION, CDR3 DOMAIN, FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CAUTION.
RX PubMed=31959982; DOI=10.1038/s41590-019-0578-8;
RA Crowther M.D., Dolton G., Legut M., Caillaud M.E., Lloyd A., Attaf M.,
RA Galloway S.A.E., Rius C., Farrell C.P., Szomolay B., Ager A., Parker A.L.,
RA Fuller A., Donia M., McCluskey J., Rossjohn J., Svane I.M., Phillips J.D.,
RA Sewell A.K.;
RT "Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer
RT targeting via the monomorphic MHC class I-related protein MR1.";
RL Nat. Immunol. 21:178-185(2020).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 136-275 (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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 136-275 (IMGT ALLELE TRAC*01).
RX PubMed=3873654; DOI=10.1073/pnas.82.10.3430;
RA Yanagi Y., Chan A., Chin B., Minden M., Mak T.W.;
RT "Analysis of cDNA clones specific for human T cells and the alpha and beta
RT chains of the T-cell receptor heterodimer from a human T-cell line.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3430-3434(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-116 (IMGT ALLELE TRAV38-2/DV8*01).
RX PubMed=9110172; DOI=10.1101/gr.7.4.330;
RA Boysen C., Simon M.I., Hood L.;
RT "Analysis of the 1.1-Mb human alpha/delta T-cell receptor locus with
RT bacterial artificial chromosome clones.";
RL Genome Res. 7:330-338(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRAV38-2/DV8*01;
RP ALLELE TRAJ31*01 AND ALLELE TRAC*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.
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).
CC -!- FUNCTION: The alpha chain of TRAV38-2DV8*01J31*01C*01/TRBV25-
CC 1*01J2S3*01C2*01 alpha-beta T cell receptor (TR) clonotype that
CC displays pan-cancer cell recognition via the invariant MR1 molecule. On
CC CD8-positive T cell clone MC.7.G5, likely recognizes tumor-specific or
CC -associated metabolite(s) essential for cancer cell survival,
CC triggering killing of many cancer cell types including lung, melanoma,
CC leukemia, colon, breast, prostate, bone and ovarian cancer cells.
CC Mediates cancer cell cytotoxicity in an HLA-independent manner. Has no
CC reactivity to healthy cells, even stressed or infected by bacteria
CC (PubMed:31959982). Antigen recognition initiates TR-CD3 clustering on
CC the cell surface and intracellular activation of LCK that
CC phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling
CC the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which
CC recruits numerous signaling molecules to form the LAT signalosome. The
CC LAT signalosome propagates signal branching to three major signaling
CC pathways, the calcium, the mitogen-activated protein kinase (MAPK)
CC kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to
CC the mobilization of transcription factors that are critical for gene
CC expression and essential for T cell differentiation into
CC effector/memory T cells (By similarity). {ECO:0000250|UniProtKB:P01848,
CC ECO:0000269|PubMed:31959982}.
CC -!- SUBUNIT: Disulfide-linked heterodimer with TRBV25-1*01J2S3*01C2*01 beta
CC chain (PubMed:31959982). The alpha-beta TR associates with the
CC transmembrane signaling CD3 coreceptor proteins to form the TR-CD3
CC (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 (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:31959982}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31959982}.
CC -!- TISSUE SPECIFICITY: Expressed in MR1-restricted CD8-positive T cells.
CC {ECO:0000269|PubMed:31959982}.
CC -!- DOMAIN: The complementarity-determining region CDR1 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
CC -!- DOMAIN: The complementarity-determining region CDR2 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
CC -!- DOMAIN: The complementarity-determining region CDR3 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
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 -!- CAUTION: This sequence is an example of a full-length TR alpha chain.
CC Pan-cancer TRAV38-2DV8*01J31*01C*01 TR alpha chain is generated by
CC somatic recombination of variable TRAV38-2DV8 (AC A0JD32) and joining
CC TRAJ31 (AC A0A075B700) gene segments spliced to constant TRAC (AC
CC P01848) gene segment. {ECO:0000269|PubMed:31959982}.
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; MN782533; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X02592; CAA26435.1; ALT_SEQ; mRNA.
DR EMBL; AE000521; AAB69036.1; -; Genomic_DNA.
DR EMBL; AC243965; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DTU3; -.
DR SMR; P0DTU3; -.
DR GlyGen; P0DTU3; 5 sites.
DR MassIVE; P0DTU3; -.
DR PeptideAtlas; P0DTU3; -.
DR GeneCards; TRA; -.
DR HGNC; HGNC:12027; TRA.
DR MalaCards; TRA; -.
DR neXtProt; NX_P0DTU3; -.
DR Proteomes; UP000005640; Unplaced.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB.
DR GO; GO:0002355; P:detection of tumor cell; IDA:UniProtKB.
DR GO; GO:0002419; P:T cell mediated cytotoxicity directed against tumor cell target; 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 Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..275
FT /note="T cell receptor alpha chain MC.7.G5"
FT /id="PRO_0000450077"
FT TRANSMEM 251..273
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P01848, ECO:0000255"
FT TOPO_DOM 274..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..116
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 154..242
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 22..116
FT /note="T cell receptor alpha variable 38-2DV8"
FT /evidence="ECO:0000305|PubMed:31959982"
FT REGION 47..53
FT /note="CDR1"
FT /evidence="ECO:0000305|PubMed:11096259"
FT REGION 71..81
FT /note="CDR2"
FT /evidence="ECO:0000305|PubMed:11096259"
FT REGION 112..124
FT /note="CDR3"
FT /evidence="ECO:0000269|PubMed:31959982,
FT ECO:0000305|PubMed:11096259"
FT REGION 119..134
FT /note="T cell receptor alpha joining 31"
FT /evidence="ECO:0000305|PubMed:31959982"
FT REGION 136..275
FT /note="T cell receptor alpha constant"
FT REGION 229..250
FT /note="Connecting peptide"
FT /evidence="ECO:0000250|UniProtKB:P01848"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P01848,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P01848,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 43..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 157..207
FT /evidence="ECO:0000250|UniProtKB:P01848"
FT DISULFID 229
FT /note="Interchain (with C-130 in TRBC1 or TRBC2)"
FT /evidence="ECO:0000250|UniProtKB:P01848"
SQ SEQUENCE 275 AA; 30989 MW; E13E6E2DD4E7695A CRC64;
MACPGFLWAL VISTCLEFSM AQTVTQSQPE MSVQEAETVT LSCTYDTSES DYYLFWYKQP
PSRQMILVIR QEAYKQQNAT ENRFSVNFQK AAKSFSLKIS DSQLGDAAMY FCAYRSAVNA
RLMFGDGTQL VVKPNIQNPD PAVYQLRDSK SSDKSVCLFT DFDSQTNVSQ SKDSDVYITD
KTVLDMRSMD FKSNSAVAWS NKSDFACANA FNNSIIPEDT FFPSPESSCD VKLVEKSFET
DTNLNFQNLS VIGFRILLLK VAGFNLLMTL RLWSS
