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FLASH GENE
Symbol MALT1 contributors: mct - updated : 16-01-2015
HGNC name mucosa associated lymphoid tissue lymphoma translocation gene 1
HGNC id 6819
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 5029 92 824 - 2008 186257
16 - 4996 91 813 - 2008 PMID: 186257
  • lacking an exon in the coding region compared to variant 1
  • maintaining the same reading frame compared to variant 1
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately
    Endocrineneuroendocrinepituitary  moderately
     parathyroid   moderately
    Lymphoid/Immunelymph node   predominantly
     tonsils   highly
    Reproductivefemale systembreastmammary gland moderately
     male systemprostate  moderately
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneactivated B lymphocyte
    Lymphoid/ImmuneB cell
    cell lineage pre B cells
    cell lines
    fluid/secretion
    at STAGE
    life cycle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a death domain
  • two Ig-like C2-type domains
  • two VDJ4 -like domains
  • a region of partial homology to caspase (ARD domain)
  • a paracaspase domain of MALT1 is a component of a gene translocation fused to the N-terminal domains of the cellular inhibitor of apoptosis protein 2
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to rattus Malt1 (88.8pc)
    ortholog to murine Malt1 (88.3pc)
    Homologene
    FAMILY
  • caspase-like protein superfamily
  • peptidase C14 family
  • CATEGORY enzyme , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text found in perinuclear structures together with Bcl-10
    basic FUNCTION
  • playing a potential role in the regulation of apoptosis
  • inducing NFKB activation and required for the normal development of B cells and for the activation of the IKK complex
  • acting as a caspase
  • mediate additional functions related to T cell activation, cleaving both the ubiquitin editing enzyme, TNFAIP3, and the C terminus of BCL10
  • have an essential role in antigen receptor-induced nuclear factor-KB (NF-KB) activation and the control of lymphocyte activation and proliferation
  • mediates antigen receptor signalling to NFKB1 by acting as a scaffold protein
  • role for MALT1 proteolytic activity in TCR-induced JNK activation and CYLD cleavage is the underlying mechanism
  • has many similarities to CASP8, even cleaving the putative target protein CYLD with comparable efficiencies, but with diametrically opposite primary substrate specificity
  • the catalytic activity of MALT1 promotes activation of canonical and non-canonical NFKB1 as well as other signalling pathways
  • protease activity of the paracaspase MALT1 is central to lymphocyte activation and lymphomagenesis
  • MALT1 protease activity is critical for controlling the mRNA stability of T cell effector genes.
  • mediates the activation of NFKB1 in response to antigen receptor signaling
  • paracaspase with structural similarity to caspases
  • CARD11/BCL10/MALT1 (CBM) signalosome mediates antigen receptor-induced NFKB1 signaling to regulate multiple lymphocyte functions
  • CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives, are involved in BCR signaling
  • central regulator of antigen receptor signaling that is frequently mutated in human lymphoma
  • differentially control lymphocyte differentiation and activation pathways and selective paracaspase blockage skews systemic immunity toward destructive autoinflammation
  • plays a key role in immunity and inflammation by regulating gene expression in lymphocytes and other immune cell types
  • CELLULAR PROCESS cell life, antiapoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    activation of NFKB inducing kinase
    a component
  • forming a trinary complex with BCL10, CARD10, IKK complex
  • CARD11-BCL10-MALT1 (CBM) complex connects T-cell receptor (TCR) signalling to the canonical IkappaB kinase (IKK)/NF (nuclear factor)-kappaB pathway
  • CARD9-BCL10-MALT1 pathway activated by SYK
  • CARD10-BCL10-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis
  • importance of MALT1 dimerization for its catalytic activity
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • death domain of MALT1 and the CARD of BCL10 also contribute to BCL10-MALT1 interactions
  • CARD10
  • fusion protein BIRC3-MALT1 can confer resistance to apoptosis, at least in part, by interacting with TRAF2 and neutralizing apoptosis promoted by DIABLO
  • CARD11 serves as a scaffold for BCL10, MALT1 and other effector proteins and regulates various signaling pathways related to the immune response
  • AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NFKB1 signaling upon T cell activation
  • MALT1-mediated RBCK1 cleavage provides a gain-of-function mechanism that is involved in the negative feedback regulation of NFKB1 signaling
  • RBCK1 is a negative regulator of lymphocyte activation cleaved by MALT1
  • cell & other
    REGULATION
    Other monoubiquitination of MALT1 is essential for its catalytic activation
    ASSOCIATED DISORDERS
    corresponding disease(s) MALTLY , IMD12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    rearranged with API2 in the t(11;18)(q21;q21) in extranodal marginal zone B-cell lymphomas, in low-grade B cell lymphoma of mucosa associated lymphoid tissue
    tumoral fusion      
    of exon 9 of MALT1 and exon 9 of MAP4 in diffuse large B-cell lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    development of selective MALT1 inhibitors as a rational strategy for the therapy of NF-kB-dependent type of cancer (diffuse large B-cell lymphoma DLBCL)
    cancerhemopathy 
    targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling
    cancerhemopathy 
    monoubiquitination of MALT1 is essential for its catalytic activation and is therefore a potential target for the treatment of ABC-DLBCL and for immunomodulation
    ANIMAL & CELL MODELS