Aliases for TRA Gene

Aliases for TRA Gene

  • T Cell Receptor Alpha Locus 2 3
  • TCRA, TRA@ 2 3
  • T-Cell Antigen Receptor, Alpha Polypeptide 3
  • M1-Specific T Cell Receptor Alpha Chain 4
  • TR Alpha Chain TRAV38-2DV8*01J31*01C*01 4
  • T Cell Receptor Alpha Chain MC.7.G5 4
  • TR Alpha Chain TRAV27*01J42*01C*01 4
  • T-Cell Receptor, Alpha (V,D,J,C) 3
  • MC.7.G5 TRA 4
  • IMD7 3
  • TCRA 3
  • TRA@ 3

External Ids for TRA Gene

Previous HGNC Symbols for TRA Gene

  • TCRA
  • TRA@

Previous GeneCards Identifiers for TRA Gene

  • GC14P022093

Summaries for TRA Gene

GeneCards Summary for TRA Gene

TRA (T Cell Receptor Alpha Locus) is a Protein Coding gene. Diseases associated with TRA include Precursor T-Cell Acute Lymphoblastic Leukemia and T-Cell Receptor-Alpha/Beta Deficiency. Among its related pathways are Immune response Function of MEF2 in T lymphocytes and Cytokines and Inflammatory Response.

UniProtKB/Swiss-Prot Summary for TRA Gene

  • The alpha chain of TRAV27*01J42*01C*01/TRBV19*01J2S7*01C*02 alpha-beta T cell receptor (TR) clonotype that is specific for HLA-A*02:01-restricted M/matrix protein 1 immunodominant epitope GILGFVFTL of influenza A virus (IAV). Classified as a public TR clonotype, it is preferentially selected in effector memory CD8-positive T cells among multiple HLA-A*02:01 carriers and confers long-lived immunity against IAV infection. Can cross-recognize sporadically emerging IAV variants by molecular mimicry, inducing immunity toward different influenza strains (PubMed:1833769, PubMed:7807026, PubMed:29997621, PubMed:27036003, PubMed:12796775, PubMed:18275829). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).
  • The alpha chain of TRAV38-2DV8*01J31*01C*01/TRBV25-1*01J2S3*01C2*01 alpha-beta T cell receptor (TR) clonotype that displays pan-cancer cell recognition via the invariant MR1 molecule. On CD8-positive T cell clone MC.7.G5, likely recognizes tumor-specific or -associated metabolite(s) essential for cancer cell survival, triggering killing of many cancer cell types including lung, melanoma, leukemia, colon, breast, prostate, bone and ovarian cancer cells. Mediates cancer cell cytotoxicity in an HLA-independent manner. Has no reactivity to healthy cells, even stressed or infected by bacteria (PubMed:31959982). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).

Gene Wiki entry for TRA Gene

Additional gene information for TRA Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TRA Gene

Genomics for TRA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TRA Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J021647 Enhancer 0.5 FANTOM5 0.3 +25.5 25548 0.5 ZSCAN16 ZNF398 HLF ZNF580 SALL2 RPGRIP1 ARL6IP1P1 TRAV1-2 lnc-OR10G2-2 OR4E2 TRA
GH14J021668 Enhancer 0.6 Ensembl ENCODE 0.3 +46.7 46697 0.4 FOXA2 ZEB2 ZNF629 ZBTB17 OR10G2 METTL17 lnc-OR4E1-4 OR4E1 OR4E2 TRA
GH14J021703 Enhancer 0.8 VISTA Ensembl 0.2 +82.2 82159 2 FEZF1 FOXA2 ZNF217 PKNOX1 MYNN MTA2 WT1 OR10G3 ENSG00000256350 TRAV2 HSALNG0099908 OR4E1 TRA
GH14J021642 Promoter 0.3 Ensembl 0.3 +21.3 21297 0.8 HSALNG0099905 TRAV1-2 lnc-OR10G2-2 OR4E2 TRA
GH14J021723 Promoter/Enhancer 0.8 Ensembl ENCODE 0.1 +101.7 101697 0.4 CTCF ZNF610 RAD21 ZNF143 ZNF654 TRAV3 HSALNG0099913 TRAV2 TRA
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TRA on the GeneHancer Hub at the UCSC Golden Path

Genomic Locations for TRA Gene

Latest Assembly
chr14:21,621,904-22,552,132
(GRCh38/hg38)
Size:
930,229 bases
Orientation:
Plus strand

Previous Assembly
chr14:22,090,057-23,021,075
(GRCh37/hg19 by Entrez Gene)
Size:
931,019 bases
Orientation:
Plus strand

Genomic View for TRA Gene

Genes around TRA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TRA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TRA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TRA Gene

Proteins for TRA Gene

  • Protein details for TRA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P0DSE1-TRAR1_HUMAN
    Recommended name:
    M1-specific T cell receptor alpha chain
    Protein Accession:
    P0DSE1

    Protein attributes for TRA Gene

    Size:
    268 amino acids
    Molecular mass:
    29608 Da
    Quaternary structure:
    • Disulfide-linked heterodimer with TRBV19*01J2S7*01C*02 beta chain. The TR primarily interacts via its CDR3-beta domain with M/matrix protein 1-derived peptide (GILGFVFTL) displayed by HLA-A*02.01 in a 'peg-notch' recognition mode (PubMed:27036003, PubMed:12796775, PubMed:18275829). The alpha-beta TR associates with the transmembrane signaling CD3 coreceptor proteins to form the TR-CD3 (TCR). The assembly of alpha-beta TR heterodimers with CD3 occurs in the endoplasmic reticulum where a single alpha-beta TR heterodimer associates with one CD3D-CD3E heterodimer, one CD3G-CD3E heterodimer and one CD247 homodimer forming a stable octomeric structure. CD3D-CD3E and CD3G-CD3E heterodimers preferentially associate with TR alpha and TR beta chains (via TM domain), respectively. The association of the CD247 homodimer is the last step of TCR assembly in the endoplasmic reticulum and is required for transport to the cell surface (By similarity).
    SequenceCaution:
    • 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};
    Miscellaneous:
    • The JM22 clone described as a variant of the public clonotype differs by one amino acid in the CDR3-alpha domain.

    Three dimensional structures from OCA and Proteopedia for TRA Gene

  • Protein details for TRA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P0DTU3-TRAR2_HUMAN
    Recommended name:
    T cell receptor alpha chain MC.7.G5
    Protein Accession:
    P0DTU3

    Protein attributes for TRA Gene

    Size:
    275 amino acids
    Molecular mass:
    30989 Da
    Quaternary structure:
    • Disulfide-linked heterodimer with TRBV25-1*01J2S3*01C2*01 beta chain (PubMed:31959982). The alpha-beta TR associates with the transmembrane signaling CD3 coreceptor proteins to form the TR-CD3 (TCR). The assembly of alpha-beta TR heterodimers with CD3 occurs in the endoplasmic reticulum where a single alpha-beta TR heterodimer associates with one CD3D-CD3E heterodimer, one CD3G-CD3E heterodimer and one CD247 homodimer forming a stable octomeric structure. CD3D-CD3E and CD3G-CD3E heterodimers preferentially associate with TR alpha and TR beta chains (via TM domain), respectively. The association of the CD247 homodimer is the last step of TCR assembly in the endoplasmic reticulum and is required for transport to the cell surface (By similarity).
    SequenceCaution:
    • 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};

neXtProt entry for TRA Gene

Post-translational modifications for TRA Gene

  • Glycosylation at Asn78, Asn167, Asn201, Asn212, and Asn248

Antibodies for research

No data available for DME Specific Peptides for TRA Gene

Domains & Families for TRA Gene

Gene Families for TRA Gene

Protein Domains for TRA Gene

Suggested Antigen Peptide Sequences for TRA Gene

GenScript: Design optimal peptide antigens:
  • TRA@ protein (Q2YD82_HUMAN)
  • TRA@ protein (Q6IPR8_HUMAN)
  • TRA@ protein (Q6IRV4_HUMAN)
  • TRA@ protein (Q6NS93_HUMAN)
  • TRA@ protein (Q6NSA0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P0DSE1

UniProtKB/Swiss-Prot:

TRAR2_HUMAN :
  • The complementarity-determining region CDR1 confers specificity to the peptide antigen. Assumes a loop structure that makes contact with HLA-A*02.01 and contributes to the stability of the TR through interaction with CDR3-beta loop.
Domain:
  • The complementarity-determining region CDR1 confers specificity to the peptide antigen. Assumes a loop structure that makes contact with HLA-A*02.01 and contributes to the stability of the TR through interaction with CDR3-beta loop.
  • The complementarity-determining region CDR2 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex.
  • The complementarity-determining region CDR3 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex.
  • The connecting peptide (CP) domain contributes to the TR-CD3 assembly and signal transduction.
  • The TM domain mediates the interaction with the CD3 subunits.
  • The complementarity-determining region CDR1 confers specificity to the metabolite antigen.
  • The complementarity-determining region CDR2 confers specificity to the metabolite antigen.
  • The complementarity-determining region CDR3 confers specificity to the metabolite antigen.
genes like me logo Genes that share domains with TRA: view

Function for TRA Gene

Molecular function for TRA Gene

UniProtKB/Swiss-Prot Function:
The alpha chain of TRAV27*01J42*01C*01/TRBV19*01J2S7*01C*02 alpha-beta T cell receptor (TR) clonotype that is specific for HLA-A*02:01-restricted M/matrix protein 1 immunodominant epitope GILGFVFTL of influenza A virus (IAV). Classified as a public TR clonotype, it is preferentially selected in effector memory CD8-positive T cells among multiple HLA-A*02:01 carriers and confers long-lived immunity against IAV infection. Can cross-recognize sporadically emerging IAV variants by molecular mimicry, inducing immunity toward different influenza strains (PubMed:1833769, PubMed:7807026, PubMed:29997621, PubMed:27036003, PubMed:12796775, PubMed:18275829). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).
UniProtKB/Swiss-Prot Function:
The alpha chain of TRAV38-2DV8*01J31*01C*01/TRBV25-1*01J2S3*01C2*01 alpha-beta T cell receptor (TR) clonotype that displays pan-cancer cell recognition via the invariant MR1 molecule. On CD8-positive T cell clone MC.7.G5, likely recognizes tumor-specific or -associated metabolite(s) essential for cancer cell survival, triggering killing of many cancer cell types including lung, melanoma, leukemia, colon, breast, prostate, bone and ovarian cancer cells. Mediates cancer cell cytotoxicity in an HLA-independent manner. Has no reactivity to healthy cells, even stressed or infected by bacteria (PubMed:31959982). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).

Phenotypes From GWAS Catalog for TRA Gene

Gene Ontology (GO) - Molecular Function for TRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0038023 signaling receptor activity IDA 31959982
genes like me logo Genes that share ontologies with TRA: view

Phenotypes for TRA Gene

genes like me logo Genes that share phenotypes with TRA: view

miRNA for TRA Gene

miRTarBase miRNAs that target TRA

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for TRA Gene

Localization for TRA Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRA Gene

Gene Ontology (GO) - Cellular Components for TRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016021 integral component of membrane IEA --
GO:0042105 alpha-beta T cell receptor complex IDA 31959982
genes like me logo Genes that share ontologies with TRA: view

No data available for Subcellular locations from COMPARTMENTS and Subcellular locations from the Human Protein Atlas (HPA) for TRA Gene

Pathways & Interactions for TRA Gene

PathCards logo

SuperPathways for TRA Gene

SuperPathway Contained pathways
1 Immune response NFAT in immune response
.56
.56
.52
.52
2 G-protein signaling N-RAS regulation pathway
.52
.52
3 G-protein signaling_Rap1A regulation pathway
-
4 G-protein signaling_Regulation of RAC1 activity
-
5 Antigen processing-Cross presentation
.51
genes like me logo Genes that share pathways with TRA: view

Pathways by source for TRA Gene

15 GeneGo (Thomson Reuters) pathways for TRA Gene
  • G-protein signaling N-RAS regulation pathway
  • G-protein signaling_Rap1A regulation pathway
  • G-protein signaling_Regulation of RAC1 activity
  • Immune response Antigen presentation by MHC class I
  • Immune response Antigen presentation by MHC class II

Interacting Proteins for TRA Gene

Gene Ontology (GO) - Biological Process for TRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002355 detection of tumor cell IDA 31959982
GO:0002419 T cell mediated cytotoxicity directed against tumor cell target IDA 31959982
genes like me logo Genes that share ontologies with TRA: view

No data available for SIGNOR curated interactions for TRA Gene

Drugs & Compounds for TRA Gene

(4) Drugs for TRA Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Coagulants Pharma 1463
Hemostatics Pharma 1815

(1) Additional Compounds for TRA Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TRA: view

Transcripts for TRA Gene

Alternative Splicing Database (ASD) splice patterns (SP) for TRA Gene

No ASD Table

Relevant External Links for TRA Gene

GeneLoc Exon Structure for
TRA

No data available for mRNA/cDNA for TRA Gene

Expression for TRA Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TRA

mRNA Expression by UniProt/SwissProt for TRA Gene:

P0DSE1-TRAR1_HUMAN
Tissue specificity: Expressed in MR1-restricted CD8-positive T cells.

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for TRA Gene

Orthologs for TRA Gene

No data available for Orthologs and Evolution for TRA Gene

Paralogs for TRA Gene

No data available for Paralogs for TRA Gene

Variants for TRA Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TRA Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
rs397514259 Pathogenic: T-cell receptor alpha/beta deficiency 22,550,664(+) G/A
NG_001332.2:g.1074699G>A
VAR_081650 - p.Gly110Ala

Additional Variant Information for TRA Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TRA

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot , dbSNP identifiers (rs#s) for variants without ClinVar clinical significance , Structural Variations from Database of Genomic Variants (DGV) and Variation tolerance for TRA Gene

Disorders for TRA Gene

MalaCards: The human disease database

(3) MalaCards diseases for TRA Gene - From: ORP and GCD

Disorder Aliases PubMed IDs
precursor t-cell acute lymphoblastic leukemia
  • precursor t-cell acute lymphoblastic leukemia/lymphoma
t-cell receptor-alpha/beta deficiency
  • tcr-alpha/beta deficiency
lysinuric protein intolerance
  • lpi
- elite association - COSMIC cancer census association via MalaCards
Search TRA in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TRA

genes like me logo Genes that share disorders with TRA: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TRA Gene

Publications for TRA Gene

  1. The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukaemia. (PMID: 3875483) Rabbitts TH … Goodfellow PN (The EMBO journal 1985) 2 3 4
  2. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. (PMID: 31959982) Crowther MD … Sewell AK (Nature immunology 2020) 3 4
  3. Pre T-cell receptor alpha (pTalpha) expression patterns and functional analysis in human T-cell lymphoblastic leukemia. (PMID: 20208138) Ivanyi P … Franzke A (Cellular oncology : the official journal of the International Society for Cellular Oncology 2010) 3 23
  4. Gene-specific signal joint modifications during V(D)J recombination of TCRAD locus genes in murine and human thymocytes. (PMID: 17015149) Touvrey C … Candéias SM (Immunobiology 2006) 3 23
  5. A structural basis for immunodominant human T cell receptor recognition. (PMID: 12796775) Stewart-Jones GB … Jones EY (Nature immunology 2003) 3 4

Products for TRA Gene

Sources for TRA Gene