MALT1
This gene has been found to be recurrently rearranged in chromosomal translocation with two other genes - baculoviral IAP repeat-containing protein 3 (also known as apoptosis inhibitor 2) and immunoglobulin heavy chain locus - in mucosa-associated lymphoid tissue lymphomas. The protein encoded by this gene may play a role in NF-kappaB activation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
Full Name
MALT1 Paracaspase
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 (PubMed:11262391, PubMed:18264101, PubMed:24074955).
Mediates BCL10 cleavage: MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion (PubMed:11262391, PubMed:18264101).
Involved in the induction of T helper 17 cells (Th17) differentiation (PubMed:11262391, PubMed:18264101).
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 (PubMed:31133753).
May also have ubiquitin ligase activity: binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity (PubMed:14695475).
Biological Process
Activation of NF-kappaB-inducing kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
B cell activationManual Assertion Based On ExperimentIBA:GO_Central
B-1 B cell differentiationIEA:Ensembl
Defense response1 PublicationNAS:UniProtKB
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Negative regulation of apoptotic process2 PublicationsNAS:UniProtKB
Nuclear exportManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentHMP:UniProtKB
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of interleukin-2 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein ubiquitination1 PublicationNAS:BHF-UCL
Positive regulation of T cell cytokine productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of T-helper 17 cell differentiationISS:UniProtKB
ProteolysisManual Assertion Based On ExperimentIDA:BHF-UCL
Proteolysis involved in cellular protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of apoptotic processManual Assertion Based On ExperimentIDA:MGI
Regulation of T cell receptor signaling pathwayIEA:Ensembl
Response to fungusIEA:Ensembl
T cell proliferationIEA:Ensembl
T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Cellular Location
Cytoplasm, perinuclear region
Nucleus
Shuttles between the nucleus and cytoplasm. Found in perinuclear structures together with BCL10.
Involvement in disease
Immunodeficiency 12 (IMD12):
A primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations include mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Levels of absolute lymphocytes and serum immunoglobulins are normal, but specific antibody titers are low despite immunization, and T-cells show impaired proliferative responses to mitogens.
A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.