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target has curated data in GtoImmuPdb
Target id: 2983
Nomenclature: MALT1 paracaspase
Gene and Protein Information | ||||||
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 |
MLT | mucosa associated lymphoid tissue lymphoma translocation gene 1 | Pcasp1 | MALT1 protease |
Database Links | |
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
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 [4]. |
Immuno Process Associations | ||
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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) [7]. 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 [7-8]. 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 [5]. |
1. Feng S, Lawrenz M, Krilov G, Placzek A, Nie Z, Trzoss L, Trzoss M, Tang H, Lagiakos R. (2021) Cyclic compounds and methods of using same. Patent number: WO2021134004A1. Assignee: Schrodinger, Inc.. Priority date: 24/12/2020. Publication date: 01/07/2021.
2. 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]
3. 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.
4. 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]
5. 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]
6. 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]
7. 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]
8. 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]
Immunoglobulin like domain containing proteins: MALT1 paracaspase. Last modified on 28/03/2024. Accessed on 07/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2983.