Target Information
Target General Information | Top | |||||
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Target ID |
T99557
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Target Name |
T-cell receptor beta constant 1 (TRBC1)
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Synonyms |
TCRBC1; BV05S1J2.2
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Gene Name |
TRBC1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
2 | Mature T-cell lymphoma [ICD-11: 2A90] | |||||
Function |
Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens. Binding of alpha-beta TR to pMH complex 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 growth and differentiation. The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity. Constant region of T cell receptor (TR) alpha chain.
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UniProt ID | ||||||
Sequence |
DLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQ
PLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIV SAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | TRBC1 | Drug Info | Phase 1/2 | Anaplastic large cell lymphoma | [1] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
CAR-T-Cell-Therapy | [+] 1 CAR-T-Cell-Therapy drugs | + | ||||
1 | TRBC1 | Drug Info | [1] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: 1-Deoxy-1-[6-(Hydroxymethyl)-2,4-Dioxo-3,4-Dihydropteridin-8(2h)-Yl]-D-Arabinitol | Ligand Info | |||||
Structure Description | Crystal structure of a human MAIT TCR in complex with a bacterial antigen bound to humanized bovine MR1 | PDB:4LCC | ||||
Method | X-ray diffraction | Resolution | 3.26 Å | Mutation | Yes | [2] |
PDB Sequence |
AGVTQTPKFQ
11 VLKTGQSMTL21 QCAQDMNHNS31 MYWYRQDPGM41 GLRLIYYSAS51 EGTTDKGEVP 61 NGYNVSRLNK71 REFSLRLESA81 APSQTSVYFC91 ASSVWTGEGS101 GELFFGEGSR 111 LTVLEDLKNV121 FPPEVAVFEP131 SEAEISHTQK141 ATLVCLATGF151 YPDHVELSWW 161 VNGKEVHSGV171 CTDPQPLKEQ181 PALNDSRYAL191 SSRLRVSATF201 WQNPRNHFRC 211 QVQFYGLSEN221 DEWKPVTQIV236 SAEAWGRA
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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References | Top | |||||
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REF 1 | ClinicalTrials.gov (NCT03590574) Phase I/II Study Evaluating AUTO4 in Patients With TRBC1 Positive T Cell Lymphoma | |||||
REF 2 | MAIT recognition of a stimulatory bacterial antigen bound to MR1. J Immunol. 2013 Nov 15;191(10):5268-77. |
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