P0DTU4 · TRBR2_HUMAN
- ProteinT cell receptor beta chain MC.7.G5
- GeneTRB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids315 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The beta 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).
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).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | alpha-beta T cell receptor complex | |
Cellular Component | plasma membrane | |
Molecular Function | signaling receptor activity | |
Biological Process | cell surface receptor signaling pathway | |
Biological Process | detection of tumor cell | |
Biological Process | T cell mediated cytotoxicity directed against tumor cell target |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameT cell receptor beta chain MC.7.G5
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0DTU4
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Features
Showing features for transmembrane, topological domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 282-304 | Helical | ||||
Sequence: TILYEILLGKATLYAVLVSALVL | ||||||
Topological domain | 305-315 | Cytoplasmic | ||||
Sequence: MAMVKRKDSRG |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MTIRLLCYMGFYFLGAGLMEA | ||||||
Chain | PRO_0000450078 | 22-315 | T cell receptor beta chain MC.7.G5 | |||
Sequence: DIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASSEARGLAEFTDTQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSRG | ||||||
Disulfide bond | 42↔110 | |||||
Sequence: CSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLC | ||||||
Glycosylation | 72 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 167↔232 | |||||
Sequence: CLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC | ||||||
Glycosylation | 206 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 267 | Interchain (with C-94 in TRAC) | ||||
Sequence: C |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in MR1-restricted CD8-positive T cells.
Interaction
Subunit
Disulfide-linked heterodimer with TRAV38-2DV8*01J31*01C*01 alpha 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 octameric 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).
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 octameric 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).
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 22-114 | Ig-like V-type | ||||
Sequence: DIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASSE | ||||||
Region | 22-114 | T cell receptor beta variable 25-1 | ||||
Sequence: DIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASSE | ||||||
Region | 46-50 | CDR1 | ||||
Sequence: MGHDK | ||||||
Region | 68-73 | CDR2 | ||||
Sequence: SYGVNS | ||||||
Region | 110-127 | CDR3 | ||||
Sequence: CASSEARGLAEFTDTQYF | ||||||
Region | 122-136 | T cell receptor beta joining 2-3 | ||||
Sequence: TDTQYFGPGTRLTVL | ||||||
Region | 138-315 | T cell receptor beta constant 2 | ||||
Sequence: DLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSRG | ||||||
Domain | 145-254 | Ig-like C1-type | ||||
Sequence: PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT | ||||||
Region | 267-281 | Connecting peptide | ||||
Sequence: CGFTSESYQQGVLSA |
Domain
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.
The connecting peptide (CP) domain is essential for signal transmission in response to antigenic stimulation, likely downstream from ZAP70 recruitment.
The TM domain mediates the interaction with the CD3 subunits.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length315
- Mass (Da)35,490
- Last updated2020-06-17 v1
- Checksum39C3AF5D0035A10A
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
MN782534 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
M12888 EMBL· GenBank· DDBJ | AAA60662.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471198 EMBL· GenBank· DDBJ | EAW51910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC244472 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC239618 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC245427 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |