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Reviewed, UniProtKB/Swiss-Prot Q9UDY8 (MALT1_HUMAN)

Last modified February 9, 2010. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Mucosa-associated lymphoid tissue lymphoma translocation protein 1
    EC=3.4.22.-
Alternative name(s):
    MALT lymphoma-associated translocation
    Paracaspase
Gene names
Name: MALT1
Synonyms: MLT
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length824 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion. Ref.8 Ref.10 Ref.12

Subunit structure

Binds through its Ig-like domains to BCL10. Forms oligomers which bind to TRAF6. Ref.9

Subcellular location

Cytoplasm › perinuclear region. Nucleus. Note: Shuttles between the nucleus and cytoplasm. Found in perinuclear structures together with BCL10. Ref.11

Tissue specificity

Highly expressed in peripheral blood mononuclear cells. Detected at lower levels in bone marrow, thymus and lymph node, and at very low levels in colon and lung.

Involvement in disease

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.

Sequence similarities

Belongs to the peptidase C14B family.

Contains 1 death domain.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

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Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DomainImmunoglobulin domain
Repeat
   Molecular functionHydrolase
Protease
   PTMDisulfide bond
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processT cell receptor signaling pathway Ref.9

Inferred from direct assay. Source: UniProtKB

activation of NF-kappaB-inducing kinase activity Ref.9

Inferred from mutant phenotype. Source: UniProtKB

anti-apoptosis Ref.3

Non-traceable author statement. Source: UniProtKB

modification-dependent protein catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear export Ref.11

Inferred from direct assay. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB cascade

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of T cell activation Ref.9

Inferred by curator. Source: UniProtKB

positive regulation of T cell cytokine production Ref.9

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of interleukin-2 production Ref.9

Inferred from mutant phenotype. Source: UniProtKB

protein oligomerization Ref.9

Inferred from direct assay. Source: UniProtKB

   Cellular componentCBM complex Ref.9

Non-traceable author statement. Source: UniProtKB

cytosol Ref.9

Inferred from Experiment. Source: Reactome

nucleus Ref.11

Inferred from direct assay. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functioncysteine-type endopeptidase activity Ref.3

Non-traceable author statement. Source: UniProtKB

protein self-association Ref.9

Inferred from physical interaction. Source: UniProtKB

signal transducer activity

Inferred from mutant phenotype. Source: UniProtKB

ubiquitin-protein ligase activity Ref.9 Ref.10

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBE2G2P606041EBI-1047372,EBI-1051028

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UDY8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9UDY8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     309-319: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 824824Mucosa-associated lymphoid tissue lymphoma translocation protein 1
PRO_0000072821

Regions

Domain39 – 12688Death
Domain125 – 20177Ig-like C2-type 1
Domain212 – 30594Ig-like C2-type 2
Region348 – 562215Caspase-like
Motif369 – 3768Nuclear export signal

Sites

Active site4151 By similarity
Active site4641 By similarity
Site126 – 1272Breakpoint for translocation to form BIRC2-MALT1
Site216 – 2172Breakpoint for translocation to form BIRC2-MALT1
Site320 – 3212Breakpoint for translocation to form BIRC2-MALT1
Site323 – 3242Breakpoint for translocation to form BIRC2-MALT1
Site329 – 3302Breakpoint for translocation to form BIRC2-MALT1

Amino acid modifications

Modified residue1351Phosphoserine Ref.13
Disulfide bond147 ↔ 190 Potential
Disulfide bond248 ↔ 290 Potential

Natural variations

Alternative sequence309 – 31911Missing in isoform 2.
VSP_000844
Natural variant6411I → V: dbSNP rs35533328.
VAR_048620

Experimental info

Mutagenesis4641C → A: Slight decrease in NF-kappa-B activation. Ref.8
Mutagenesis6531E → A: Abolishes binding to TRAF6. Ref.9
Mutagenesis8061E → A: Abolishes binding to TRAF6. Ref.9

Secondary structure

1 .............. 824
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 28AFB80DA025F8AB

FASTA82492,272
        10         20         30         40         50         60 
MSLLGDPLQA LPPSAAPTGP LLAPPAGATL NRLREPLLRR LSELLDQAPE GRGWRRLAEL 

        70         80         90        100        110        120 
AGSRGRLRLS CLDLEQCSLK VLEPEGSPSL CLLKLMGEKG CTVTELSDFL QAMEHTEVLQ 

       130        140        150        160        170        180 
LLSPPGIKIT VNPESKAVLA GQFVKLCCRA TGHPFVQYQW FKMNKEIPNG NTSELIFNAV 

       190        200        210        220        230        240 
HVKDAGFYVC RVNNNFTFEF SQWSQLDVCD IPESFQRSVD GVSESKLQIC VEPTSQKLMP 

       250        260        270        280        290        300 
GSTLVLQCVA VGSPIPHYQW FKNELPLTHE TKKLYMVPYV DLEHQGTYWC HVYNDRDSQD 

       310        320        330        340        350        360 
SKKVEIIIGR TDEAVECTED ELNNLGHPDN KEQTTDQPLA KDKVALLIGN MNYREHPKLK 

       370        380        390        400        410        420 
APLVDVYELT NLLRQLDFKV VSLLDLTEYE MRNAVDEFLL LLDKGVYGLL YYAGHGYENF 

       430        440        450        460        470        480 
GNSFMVPVDA PNPYRSENCL CVQNILKLMQ EKETGLNVFL LDMCRKRNDY DDTIPILDAL 

       490        500        510        520        530        540 
KVTANIVFGY ATCQGAEAFE IQHSGLANGI FMKFLKDRLL EDKKITVLLD EVAEDMGKCH 

       550        560        570        580        590        600 
LTKGKQALEI RSSLSEKRAL TDPIQGTEYS AESLVRNLQW AKAHELPESM CLKFDCGVQI 

       610        620        630        640        650        660 
QLGFAAEFSN VMIIYTSIVY KPPEIIMCDA YVTDFPLDLD IDPKDANKGT PEETGSYLVS 

       670        680        690        700        710        720 
KDLPKHCLYT RLSSLQKLKE HLVFTVCLSY QYSGLEDTVE DKQEVNVGKP LIAKLDMHRG 

       730        740        750        760        770        780 
LGRKTCFQTC LMSNGPYQSS AATSGGAGHY HSLQDPFHGV YHSHPGNPSN VTPADSCHCS 

       790        800        810        820 
RTPDAFISSF AHHASCHFSR SNVPVETTDE IPFSFSDRLR ISEK

« Hide

Isoform 2.

Checksum: 45D05E0DBF81DF5B
Show »

FASTA81391,081

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References

« Hide 'large scale' references
[1]"The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas."
Dierlamm J., Baens M., Wlodarska I., Stefanova-Ouzounova M., Hernandez J.M., Hossfeld D.K., De Wolf-Peeters C., Hagemeijer A., Van den Berghe H., Marynen P.
Blood 93:3601-3609(1999) [PubMed: 10339464] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION.
[2]"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., Motegi M., Tamura A., Suzuki R., Hosokawa Y., Suzuki H., Ota H., Nakamura S., Morishima Y., Taniwaki M., Seto M.
Oncogene 18:5785-5794(1999) [PubMed: 10523859] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHROMOSOMAL TRANSLOCATION.
[3]"Identification of paracaspases and metacaspases. Two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma."
Uren A.G., O'Rourke K., Aravind L., Pisabarro M.T., Seshagiri S., Koonin E.V., Dixit V.M.
Mol. Cell 6:961-967(2000) [PubMed: 11090634] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION.
Tissue: Kidney.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: B-cell.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 598-824.
Tissue: Testis.
[6]"API1-MALT1-MLT is involved in mucosa-associated lymphoid tissue lymphoma with t(11;18).(q21;q21)."
Suzuki H., Motegi M., Akagi T., Hosokawa Y., Seto M.
Blood 94:3270-3271(1999) [PubMed: 10610122] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[7]"API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products."
Motegi M., Yonezumi M., Suzuki H., Suzuki R., Hosokawa Y., Hosaka S., Kodera Y., Morishima Y., Nakamura S., Seto M.
Am. J. Pathol. 156:807-812(2000) [PubMed: 10702396] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION.
[8]"Bcl10 and MALT1, independent targets of chromosomal translocation in MALT lymphoma, cooperate in a novel NF-kappa B signaling pathway."
Lucas P.C., Yonezumi M., Inohara N., McAllister-Lucas L.M., Abazeed M.E., Chen F.F., Yamaoka S., Seto M., Nunez G.
J. Biol. Chem. 276:19012-19019(2001) [PubMed: 11262391] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-464.
[9]"The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
Mol. Cell 14:289-301(2004) [PubMed: 15125833] [Abstract]
Cited for: OLIGOMERIZATION, INTERACTION WITH TRAF6, MUTAGENESIS OF GLU-653 AND GLU-806.
[10]"Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO."
Zhou H., Wertz I., O'Rourke K., Ultsch M., Seshagiri S., Eby M., Xiao W., Dixit V.M.
Nature 427:167-171(2004) [PubMed: 14695475] [Abstract]
Cited for: FUNCTION AS A UBIQUITIN LIGASE.
[11]"MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10."
Nakagawa M., Hosokawa Y., Yonezumi M., Izumiyama K., Suzuki R., Tsuzuki S., Asaka M., Seto M.
Blood 106:4210-4216(2005) [PubMed: 16123224] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
[12]"The proteolytic activity of the paracaspase MALT1 is key in T cell activation."
Rebeaud F., Hailfinger S., Posevitz-Fejfar A., Tapernoux M., Moser R., Rueda D., Gaide O., Guzzardi M., Iancu E.M., Rufer N., Fasel N., Thome M.
Nat. Immunol. 9:272-281(2008) [PubMed: 18264101] [Abstract]
Cited for: FUNCTION.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135, MASS SPECTROMETRY.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF130356 mRNA. Translation: AAD38507.2.
AB026118 mRNA. Translation: BAA83099.1.
AF316597 mRNA. Translation: AAG38589.1.
BC030143 mRNA. Translation: AAH30143.1.
AL137399 mRNA. Translation: CAB70725.1.
IPIIPI00009540.
IPI00183015.
PIRT46456.
RefSeqNP_006776.1.
NP_776216.1.
UniGeneHs.601217

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2G7RX-ray2.70A/B29-126[»]
3BFOX-ray1.15A/B/C/D225-308[»]
3K0WX-ray2.80A128-337[»]
SMRQ9UDY8. Positions 14-134, 97-198, 343-557.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UDY8. 2 interactions.
STRINGQ9UDY8.

Protein family/group databases

MEROPSC14.026.

PTM databases

PhosphoSiteQ9UDY8.

Proteomic databases

PRIDEQ9UDY8.

Genome annotation databases

EnsemblENST00000348428; ENSP00000319279; ENSG00000172175; Homo sapiens. [Genome view]
GeneID10892.
KEGGhsa:10892.
UCSCuc002lhm.1. human.
uc002lhn.1. human.

Organism-specific databases

CTD10892.
GeneCardsGC18P054489.
H-InvDBHIX0022551.
HGNCHGNC:6819. MALT1.
HPACAB004494.
HPA003865.
MIM604860. gene.
Orphanet52417. MALT lymphoma.
PharmGKBPA30568.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17804.
HOGENOMHBG446517.
HOVERGENQ9UDY8.
InParanoidQ9UDY8.
OMAGTYWCHV.
OrthoDBEOG9NKFG5.
PhylomeDBQ9UDY8.

Enzyme and pathway databases

Pathway_Interaction_DBbcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
ReactomeREACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressQ9UDY8.
BgeeQ9UDY8.
CleanExHS_MALT1.
GenevestigatorQ9UDY8.
GermOnlineENSG00000172175. Homo sapiens.

Family and domain databases

InterProIPR011029. DEATH-like.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011600. Pept_C14_cat.
IPR001309. Pept_C14_ICE_p20.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 2 hits.
PfamPF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50208. CASPASE_P20. 1 hit.
PS50017. DEATH_DOMAIN. False negative.
PS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio41357.
SOURCESearch...

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Entry information

Entry nameMALT1_HUMAN
AccessionPrimary (citable) accession number: Q9UDY8
Secondary accession number(s): Q9NTB7, Q9ULX4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 1, 2000
Last modified: February 9, 2010
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents