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FLASH GENE

Symbol

MALT1

contributors: mct - updated : 16-01-2016

HGNC name	mucosa associated lymphoid tissue lymphoma translocation gene 1
HGNC id	6819

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006785 17 - 5029 NP_006776 92 824 - 2008 186257 NM_173844 16 - 4996 NP_776216 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)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       moderately Endocrine neuroendocrine pituitary     moderately   parathyroid       moderately Lymphoid/Immune lymph node       predominantly   tonsils       highly Reproductive female system breast mammary gland   moderately   male system prostate     moderately Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune activated B lymphocyte Lymphoid/Immune B 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
	novel role for MALT1 in CARD14-induced signaling

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
	CARD14 recruits BCL10 and MALT1 to form the CARD-BCL10-MALT1 complex, which modulates NFKB1 and MAPK signalling pathway

cell & other

REGULATION

Other

monoubiquitination of MALT1 is essential for its catalytic activation

ASSOCIATED DISORDERS

corresponding disease(s)

MALTLY , IMD12

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer hemopathy   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) cancer hemopathy   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 cancer hemopathy   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