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MALT1 paracaspase

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2983

Nomenclature: MALT1 paracaspase

Family: Immunoglobulin like domain containing proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 824 18q21.32 MALT1 MALT1 paracaspase
Mouse - 832 18 E1 Malt1 MALT1 paracaspase
Rat - - 18q12.1 Malt1 MALT1 paracaspase
Gene and Protein Information Comments
Isoform b (813 aa) translated from the human gene lacks an in-frame exon in the coding region, compared to isoform a (824 aa).
Previous and Unofficial Names Click here for help
MLT | mucosa associated lymphoid tissue lymphoma translocation gene 1 | Pcasp1 | MALT1 protease
Database Links Click here for help
Alphafold Q9UDY8 (Hs), Q2TBA3 (Mm)
ChEMBL Target CHEMBL3632452 (Hs)
Ensembl Gene ENSG00000172175 (Hs), ENSMUSG00000032688 (Mm), ENSRNOG00000017181 (Rn)
Entrez Gene 10892 (Hs), 240354 (Mm), 307366 (Rn)
Human Protein Atlas ENSG00000172175 (Hs)
KEGG Gene hsa:10892 (Hs), mmu:240354 (Mm), rno:307366 (Rn)
OMIM 604860 (Hs)
Pharos Q9UDY8 (Hs)
RefSeq Nucleotide NM_006785 (Hs), NM_172833 (Mm)
RefSeq Protein NP_006776 (Hs), NP_766421 (Mm)
UniProtKB Q9UDY8 (Hs), Q2TBA3 (Mm)
Wikipedia MALT1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
JNJ-67856633 Small molecule or natural product Hs Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 7.4x10-8 M) [2]
Description: Inhibition in an in vitro biochemical assay.
safimaltib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 7.4x10-8 M) [2]
pecazine Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 5
⤷ pIC50 6.3 (IC50 5.1x10-7 M) [5]
Description: In an enzyme activity assay.
compound 20c [PMID: 34181850] Small molecule or natural product Hs Inhibition 5.3 pIC50 1
⤷ pIC50 5.3 (IC50 5.3x10-6 M) [1]
Immunopharmacology Comments
MALT1 inhibition is considered a tractable mechanism for the treatment of severe autoimmune diseases. The MALT1 inhibitory action of pecazine (a.k.a. mepazine) is reported to be effecacious in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis [3].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
General Comments
MALT1 acts as a scaffolding protein in the formation of the CARD11-BCL10-MALT1 (CBM) signalosome complex and promotes the recruitment of signaling factors (e.g. TRAF6, TAK1 and NEMO) [6]. MALT1 genetic translocations have been identified in mucosa-associated lymphoid tissue (MALT) lymphoma, that cause constitutive NF-κB activation, malignant B cell transformation and tumorigenesis [6-7]. The caspase activity of MALT1 is required for activation of NF-κB and optimal T cell activation. MALT1 inhibitors have been shown to kill MALT1-dependent lymphomas in vitro and in vivo [4].

References

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1. Liang X, Sun C, Li C, Yu H, Wei X, Liu X, Bao W, Shi Y, Sun X, Khamrakulov M et al.. (2021) Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma. J Med Chem, 64 (13): 9217-9237. [PMID:34181850]

2. Lu T, Allison BD, Barbay JK, Connolly PJ, Cummings MD, Diels G, Edwards JP, Kreutter KD, Philippar U, Shen F et al.. (2018) Pyrazole derivatives as malt1 inhibitors. Patent number: WO2018119036A1. Assignee: Janssen Biotech, Inc.. Priority date: 21/12/2016. Publication date: 28/06/2018.

3. Mc Guire C, Elton L, Wieghofer P, Staal J, Voet S, Demeyer A, Nagel D, Krappmann D, Prinz M, Beyaert R et al.. (2014) Pharmacological inhibition of MALT1 protease activity protects mice in a mouse model of multiple sclerosis. J Neuroinflammation, 11: 124. [PMID:25043939]

4. Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, Peter von Kries J, Hadian K et al.. (2012) Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell, 22 (6): 825-37. [PMID:23238017]

5. Schlauderer F, Lammens K, Nagel D, Vincendeau M, Eitelhuber AC, Verhelst SH, Kling D, Chrusciel A, Ruland J, Krappmann D et al.. (2013) Structural analysis of phenothiazine derivatives as allosteric inhibitors of the MALT1 paracaspase. Angew Chem Int Ed Engl, 52 (39): 10384-7. [PMID:23946259]

6. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM. (2000) Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell, 6 (4): 961-7. [PMID:11090634]

7. Zhou H, Du MQ, Dixit VM. (2005) Constitutive NF-kappaB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity. Cancer Cell, 7 (5): 425-31. [PMID:15894263]

How to cite this page

Immunoglobulin like domain containing proteins: MALT1 paracaspase. Last modified on 03/02/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2983.