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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
Corresponding disease
IMD12 immunodeficiency 12
MALTLY mucosa-associated lymphoid tissue (MALT) lymphoma
Location 18q21.32      Physical location : 56.338.617 - 56.417.370
Synonym name
  • paracaspase 1
  • caspase-like protein
  • MALT lymphoma-associated translocation
  • Synonym symbol(s) MLT, MLT1, DKFZp434L132, IMD12, PCASP1
    EC.number 3.4.22.-
    DNA
    TYPE functioning gene
    STRUCTURE 78.75 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    TXNL 18q21.2 thioredoxin-like, 32kDa WDR7 18q21.1-q22 WD repeat domain 7 MGC33608 18q21.31 hypothetical protein MGC33608 SIAT8C 18q21.2 sialyltransferase 8C (alpha2,3Galbeta1,4GlcNAcalpha 2,8-sialyltransferase) ONECUT2 18q21.1-q21.2 one cut domain, family member 2 FECH 18q21.2 ferrochelatase (protoporphyria) NARS 18q21.2-q21.3 asparaginyl-tRNA synthetase ATP8B1 18q21 ATPase, Class I, type 8B, member 1 LOC284288 18q21.31 similar to Ribosomal protein L24-like LOC388476 18 similar to Nonhistone chromosomal protein HMG-14 (High-mobility group nucleosome binding domain 1) NEDD4L 18q21.2 neural precursor cell expressed, developmentally down-regulated 4-like HAK 18q21.31-q21.32 heart alpha-kinase MALT1 18q21 mucosa associated lymphoid tissue lymphoma translocation gene 1 FLJ10697 LOC390858 18 similar to RIKEN cDNA 5330437I02 gene LOC388477 18 LOC388477 LOC90701 18q21.32 similar to signal peptidase complex (18kD) GRP 18q21.31 gastrin-releasing peptide RAX 18q21.31 retina and anterior neural fold homeobox CPLX4 18q21.32 complexin 4 LMAN1 18q21.3-q22 lectin, mannose-binding, 1 FLJ30681 18q21.32 KIAA1983 protein LOC219542 18q21.32 similar to 40S ribosomal protein S26 LOC390859 18 similar to Chain A, Crystal Structure Of The R463a Mutant Of Human Glutamate Dehydrogenase LOC390860 18 similar to 60S acidic ribosomal protein P0 (L10E) PMAIP1 18q21.32 phorbol-12-myristate-13-acetate-induced protein 1 LOC147072 18q21.32 similar to nuclear factor (erythroid-derived 2)-like 3; NF-E2-related factor 3 LOC388478 18 similar to serologically defined colon cancer antigen 3 LOC284289 18q21.32 similar to TERA protein LOC388479 18 similar to 40S ribosomal protein S3a LOC342784 18q21.32 similar to TFIIH basal transcription factor complex p62 subunit (Basic transcription factor 62 kDa subunit) (BTF2-p62) (General transcription factor IIH polypeptide 1) MC4R 18q21.32 melanocortin 4 receptor MRPS5P4 18q21 mitochondrial ribosomal protein S5 pseudogene LOC220147 18q21.32 similar to C-terminal binding protein 2 isoform 2; ribeye CDH20 18q22-q23 cadherin 20, type 2 LOC388480 18 LOC388480
    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