MALT1 (mucosa associated lymphoid tissue lymphoma translocation gene 1)

2001-09-01 Mathijs Baens , Peter Marynen Affiliation

Center for Human Genetics, Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Catholic University of Leuven, Leuven, Belgium

Identity

HGNC

MALT1

LOCATION

18q21.32

LOCUSID

10892

ALIAS

IMD12,MLT,MLT1,PCASP1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

centromere to telomere orientation; 17 exons spread over 80 kb of genomic sequence, start codon in exon1, stop in exon 17

Transcription

2 alternative transcripts, probably due to alternative polyadenylation.

Proteins

MALT1 protein - Mathijs Baens , Peter Marynen

Description

92 kDa; 824 amino acids; The prodomain contains a Death Domain (homotypic interaction module), followed by two immunoglobulin-like domains, a predicted caspace-like proteolytic domain (p20) and a region with homology to the murine VDJ4 sequence

Localisation

cytoplasmic

Homology

with the predicted ORF from the C. elegans F22D3.6

Implicated in

Entity name

t(11;18)(q21;q21) / marginal zone B-cell lymphoma ofMALT-type --> BIRC3 - MALT1

Disease

B-cell non Hodgkin lymphoma (NHL); marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT); found in extranodal MZBCL or MALT-type (50%), absent in splenic and nodal MZBCL

Prognosis

For gastric MALT-type lymphomas, t(11;18) is a clonal marker for resistance to Helicobacter pylori eradication therapy and antigen independent growth

Cytogenetics

t(11;18) is frequently associated with deletions affecting 3 API2 on chromosome 11 or 5 MALT1 on chromosome 18.

Hybrid gene

5 API2 on chromosome 11q21 translocated on chromosome 18 in frame with 3 MALT1. Deletions often exclude the expression of the reciprocal 5 MLT API2 3 transcript.

BIRC3/MALT1 fusion protein - Mathijs Baens, Peter Marynen

Fusion protein

All MALT-type lymphomas reported with a t(11;18) express an in frame API2-MLT fusion protein with consistently the three BIR domains of API2 fused to the caspace p20 domain and VDJ4-like domain of MLT.

Oncogenesis

Transient expression of the API2-MLT fusion protein acitvates an NF-KB luciferase reporter construct, suggesting the involvement of this signaling cascade in MALT lymphomagenesis

Breakpoints

Bibliography

Pubmed ID	Last Year	Title	Authors
10523859	1999	A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.	Akagi T et al
10751367	2000	The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation.	Baens M et al
11066071	2000	Structure of the MLT gene and molecular characterization of the genomic breakpoint junctions in the t(11;18)(q21;q21) of marginal zone B-cell lymphomas of MALT type.	Baens M et al
10979968	2000	Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes.	Dierlamm J et al
10907943	2000	The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type.	Maes B et al
11090634	2000	Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.	Uren AG et al

Other Information

Locus ID:

NCBI: 10892
MIM: 604860
HGNC: 6819
Ensembl: ENSG00000172175

Variants:

dbSNP: 10892
ClinVar: 10892
TCGA: ENSG00000172175
COSMIC: MALT1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000172175	ENST00000345724	Q9UDY8
ENSG00000172175	ENST00000591792	K7EP42
ENSG00000172175	ENST00000648670	A0A3B3IS82
ENSG00000172175	ENST00000649217	Q9UDY8
ENSG00000172175	ENST00000650045	A0A3B3IS32

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
T cell receptor signaling pathway	KEGG	ko04660
B cell receptor signaling pathway	KEGG	ko04662
T cell receptor signaling pathway	KEGG	hsa04660
B cell receptor signaling pathway	KEGG	hsa04662
Tuberculosis	KEGG	ko05152
Tuberculosis	KEGG	hsa05152
NF-kappa B signaling pathway	KEGG	hsa04064
NF-kappa B signaling pathway	KEGG	ko04064
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
TCR signaling	REACTOME	R-HSA-202403
Downstream TCR signaling	REACTOME	R-HSA-202424
Signaling by the B Cell Receptor (BCR)	REACTOME	R-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)	REACTOME	R-HSA-1168372
Activation of NF-kappaB in B cells	REACTOME	R-HSA-1169091
Innate Immune System	REACTOME	R-HSA-168249
Fc epsilon receptor (FCERI) signaling	REACTOME	R-HSA-2454202
FCERI mediated NF-kB activation	REACTOME	R-HSA-2871837
C-type lectin receptors (CLRs)	REACTOME	R-HSA-5621481
CLEC7A (Dectin-1) signaling	REACTOME	R-HSA-5607764
CLEC7A/inflammasome pathway	REACTOME	R-HSA-5660668

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19112107	2009	CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex.	131
17948050	2007	Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation.	88
19494296	2009	A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains.	84
17101977	2007	CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.	81
23238016	2012	MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo.	81
19897720	2009	Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.	79
23238017	2012	Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL.	79
19841089	2009	Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells.	76
21448133	2011	T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1.	76
21873235	2011	Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines.	76

Citation

Mathijs Baens ; Peter Marynen

MALT1 (mucosa associated lymphoid tissue lymphoma translocation gene 1)

Atlas Genet Cytogenet Oncol Haematol. 2001-09-01

Online version: http://atlasgeneticsoncology.org/gene/240/malt1-(mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene-1)