Mucosa-associated lymphoid tissue lymphoma translocation protein 1

Function

Protease that enhances BCL10-induced activation: acts via formation of CBM complexes that channel adaptive and innate immune signaling downstream of CARD domain-containing proteins (CARD9, CARD11 and CARD14) to activate NF-kappa-B and MAP kinase p38 pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Mediates BCL10 cleavage: MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion. Involved in the induction of T helper 17 cells (Th17) differentiation. Cleaves RC3H1 and ZC3H12A in response to T-cell receptor (TCR) stimulation which releases their cooperatively repressed targets to promote Th17 cell differentiation (By similarity). Also mediates cleavage of N4BP1 in T-cells following TCR-mediated activation, leading to N4BP1 inactivation. May also have ubiquitin ligase activity: binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity.

Classification

Family (Pfam)

PF13895 Ig_2, PF13927 Ig_3, PF18703 MALT1_Ig, PF00656 Peptidase_C14

InterPro

Caspase-like_dom_sf, Caspase-related_regulators, DEATH-like_dom_sf, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_sub, Ig_sub2, MALT1_Death, MALT1_Ig, MALT1_IG-like_dom_sf, Pept_C14_caspase, Pept_C14_p20

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 26

• 2G7R X-ray 2.70A
• 3BFO X-ray 1.15A
• 3K0W X-ray 2.80A
• 3UO8 X-ray 1.90A
• 3UOA X-ray 1.75A
• 3V4O X-ray 2.10A
• 3V55 X-ray 1.81A
• 4I1P X-ray 2.40A
• 4I1R X-ray 2.70A
• 6F7I X-ray 2.43A
• 6GK2 EM 4.90A
• 6H4A X-ray 2.65A
• … and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 32

• GO:0032449 CBM complex
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005634 nucleus
• GO:0048471 perinuclear region of cytoplasm
• GO:0002096 polkadots
• GO:0032991 protein-containing complex
• GO:0004197 cysteine-type endopeptidase activity
• GO:0061133 endopeptidase activator activity
• GO:0004175 endopeptidase activity
• GO:0042802 identical protein binding
• GO:0008233 peptidase activity
• GO:0002020 protease binding
• GO:0036094 small molecule binding
• GO:0004842 ubiquitin-protein transferase activity
• GO:0042113 B cell activation
• GO:0006952 defense response
• GO:0045087 innate immune response
• GO:0031663 lipopolysaccharide-mediated signaling pathway
• GO:0043066 negative regulation of apoptotic process
• GO:0051168 nuclear export
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:0032731 positive regulation of interleukin-1 beta production
• GO:0032743 positive regulation of interleukin-2 production
• GO:0031398 positive regulation of protein ubiquitination
• GO:0002726 positive regulation of T cell cytokine production
• GO:2000321 positive regulation of T-helper 17 cell differentiation
• GO:0006508 proteolysis
• GO:0051603 proteolysis involved in protein catabolic process
• GO:0042981 regulation of apoptotic process
• GO:0043122 regulation of canonical NF-kappaB signal transduction
• GO:0050852 T cell receptor signaling pathway

Disease associations

• combined immunodeficiency due to MALT1 deficiency MONDO:0014197

Drugs targeting this protein · 1

• MEPAZINE ACETATE inhibitor

Related proteins · sequence + function similarity

• Mucosa-associated lymphoid tissue lymphoma translocation protein 1 homolog 0.98
• CASP8 and FADD-like apoptosis regulator 0.67
• CASP8 and FADD-like apoptosis regulator 0.67
• Caspase-2 0.61
• UNC5C-like protein 0.60
• CASP8 and FADD-like apoptosis regulator 0.60
• Caspase-2 0.60
• Caspase-2 0.60
• UNC5C-like protein 0.60
• Interleukin-17 receptor D 0.58
• Caspase-8 0.58
• Interleukin-17 receptor D 0.56

Co-cited proteins · studied together in the literature

• NEDD4-binding protein 1 1 shared papers
• B-cell lymphoma/leukemia 10 4 shared papers
• Metacaspase-1 1 shared papers
• Paracaspase 1 shared papers
• Caspase recruitment domain-containing protein 11 2 shared papers
• NF-kappa-B essential modulator 2 shared papers
• Caspase recruitment domain-containing protein 14 1 shared papers

Literature · 20 cited papers

• N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation. Nat. Microbiol. · 2019
• Germline hypomorphic CARD11 mutations in severe atopic disease. Nat. Genet. · 2017
• The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO Rep. · 2016
• Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol. Cell · 2013
• A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency. J. Allergy Clin. Immunol. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat. Immunol. · 2008
• The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
• MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Blood · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 8 more in the literature graph