Target Information
Target General Information | Top | |||||
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Target ID |
T08298
(Former ID: TTDI02550)
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Target Name |
Granzyme B (GZMB)
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Synonyms |
Tcell serine protease 13E; SECT; Lymphocyte protease; Human lymphocyte protein; Granzyme2; GZMB; Fragmentin2; Cytotoxic Tlymphocyte proteinase 2; Cathepsin Glike 1; CTSGL1; CTLA1; C11
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Gene Name |
GZMB
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Target Type |
Literature-reported target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Aneurysm/dissection [ICD-11: BD50] | |||||
Function |
This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9and 10 to give rise to active enzymes mediating apoptosis.
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 3.4.21.79
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Sequence |
MQPILLLLAFLLLPRADAGEIIGGHEAKPHSRPYMAYLMIWDQKSLKRCGGFLIRDDFVL
TAAHCWGSSINVTLGAHNIKEQEPTQQFIPVKRPIPHPAYNPKNFSNDIMLLQLERKAKR TRAVQPLRLPSNKAQVKPGQTCSVAGWGQTAPLGKHSHTLQEVKMTVQEDRKCESDLRHY YDSTIELCVGDPEIKKTSFKGDSGGPLVCNKVAQGIVSYGRNNGMPPRACTKVSSFVHWI KKTMKRY Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A08298 | |||||
HIT2.0 ID | T80Q3D |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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 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 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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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Apoptosis | hsa04210 | Affiliated Target |
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Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
Natural killer cell mediated cytotoxicity | hsa04650 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 3.34E-04 |
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Closeness centrality | 2.19E-01 | Radiality | 1.38E+01 | Clustering coefficient | 4.76E-02 |
Neighborhood connectivity | 2.54E+01 | Topological coefficient | 1.66E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
1 | Natural killer cell mediated cytotoxicity | |||||
2 | Type I diabetes mellitus | |||||
3 | Transcriptional misregulation in cancer | |||||
4 | Autoimmune thyroid disease | |||||
5 | Allograft rejection | |||||
6 | Graft-versus-host disease | |||||
NetPath Pathway | [+] 4 NetPath Pathways | + | ||||
1 | IL9 Signaling Pathway | |||||
2 | TCR Signaling Pathway | |||||
3 | IL2 Signaling Pathway | |||||
4 | IL4 Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Apoptosis signaling pathway | |||||
PID Pathway | [+] 4 PID Pathways | + | ||||
1 | IL12-mediated signaling events | |||||
2 | Caspase Cascade in Apoptosis | |||||
3 | Downstream signaling in naï | |||||
4 | ||||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | NOTCH2 intracellular domain regulates transcription | |||||
WikiPathways | [+] 5 WikiPathways | + | ||||
1 | Oxidative phosphorylation | |||||
2 | Signaling by NOTCH2 | |||||
3 | Apoptosis | |||||
4 | Allograft Rejection | |||||
5 | Intrinsic Pathway for Apoptosis |
References | Top | |||||
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REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2369). | |||||
REF 2 | Discovery of potent, selective human granzyme B inhibitors that inhibit CTL mediated apoptosis. Bioorg Med Chem Lett. 2002 Aug 19;12(16):2197-200. |
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