Target Information
Target General Information | Top | |||||
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Target ID |
T58080
(Former ID: TTDR01280)
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Target Name |
Beta-2-microglobulin (B2M)
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Synonyms |
Beta-2-microglobulin
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Gene Name |
B2M
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation.
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UniProt ID | ||||||
Sequence |
MSRSVALAVLALLSLSGLEAIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLL
KNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A00165 ; BADD_A01863 ; BADD_A02205 ; BADD_A02399 ; BADD_A06083 | |||||
HIT2.0 ID | T65CQU |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Urea | Ligand Info | |||||
Structure Description | Crystal Structures of HLA-B*1501 in Complex with Peptides from Human UbcH6 and Epstein-Barr Virus EBNA-3 | PDB:1XR9 | ||||
Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [2] |
PDB Sequence |
IQRTPKIQVY
10 SRHPAENGKS20 NFLNCYVSGF30 HPSDIEVDLL40 KNGERIEKVE50 HSDLSFSKDW 60 SFYLLYYTEF70 TPTEKDEYAC80 RVNHVTLSQP90 KIVKWDRDM
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Ligand Name: Beta-D-Glucose | Ligand Info | |||||
Structure Description | Human CD1d presenting alpha-Galactosylceramide in complex with VHH nanobody 1D22 | PDB:6V7Z | ||||
Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | No | [3] |
PDB Sequence |
MIQRTPKIQV
9 YSRHPAENGK19 SNFLNCYVSG29 FHPSDIEVDL39 LKNGERIEKV49 EHSDLSFSKD 59 WSFYLLYYTE69 FTPTEKDEYA79 CRVNHVTLSQ89 PKIVKWDRD
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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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Antigen processing and presentation | hsa04612 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 34 | Degree centrality | 3.65E-03 | Betweenness centrality | 2.77E-03 |
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Closeness centrality | 2.10E-01 | Radiality | 1.37E+01 | Clustering coefficient | 1.23E-01 |
Neighborhood connectivity | 1.06E+01 | Topological coefficient | 6.59E-02 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
References | Top | |||||
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REF 1 | Identification of beta2-microglobulin as a potential target for ovarian cancer. Cancer Biol Ther. 2009 Dec;8(24):2323-8. | |||||
REF 2 | Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype. Acta Crystallogr D Biol Crystallogr. 2006 Nov;62(Pt 11):1300-10. | |||||
REF 3 | A single-domain bispecific antibody targeting CD1d and the NKT T-cell receptor induces a potent antitumor response.. doi:10.1038/s43018-020-00111-6. |
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