Reviewed, UniProtKB/Swiss-Prot Q9UDY8 (MALT1_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	824 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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 BCL-10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion.
Subunit structure	Binds through its Ig-like domains to BCL10. Forms oligomers which bind to TRAF6.
Subcellular location	Cytoplasm › perinuclear region. Nucleus. Note= Shuttles between the nucleus and cytoplasm. Found in perinuclear structures together with BCL10.
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 C14 family. Contains 1 death domain. Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Domain	Immunoglobulin domain Repeat
Molecular function	Hydrolase Protease
Technical term	3D-structure
Gene Ontology (GO)
Biological process	T 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 defense response Ref.2 Non-traceable author statement. Source: UniProtKB 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 component	CBM 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
Molecular function	cysteine-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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2G2	P60604	1	EBI-1047372,EBI-1051028

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 824

824

Mucosa-associated lymphoid tissue lymphoma translocation protein 1

PRO_0000072821

Regions

Domain

39 – 126

88

Death

Domain

125 – 201

77

Ig-like C2-type 1

Domain

212 – 305

94

Ig-like C2-type 2

Region

348 – 562

215

Caspase-like

Motif

369 – 376

8

Nuclear export signal

Sites

Active site

415

1

By similarity

Active site

464

1

By similarity

Site

126 – 127

2

Breakpoint for translocation to form BIRC2-MALT1

Site

216 – 217

2

Breakpoint for translocation to form BIRC2-MALT1

Site

320 – 321

2

Breakpoint for translocation to form BIRC2-MALT1

Site

323 – 324

2

Breakpoint for translocation to form BIRC2-MALT1

Site

329 – 330

2

Breakpoint for translocation to form BIRC2-MALT1

Amino acid modifications

Disulfide bond

147 ↔ 190

Potential

Disulfide bond

248 ↔ 290

Potential

Natural variations

Alternative sequence

309 – 319

11

Missing in isoform 2.

VSP_000844

Experimental info

Mutagenesis

464

1

C → A: Slight decrease in NF-kappa-B activation

Mutagenesis

653

1

E → A: Abolishes binding to TRAF6

Mutagenesis

806

1

E → A: Abolishes binding to TRAF6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

824

Helix Strand Turn

Details...

Helix

30 – 32

3

Helix

35 – 45

11

Helix

54 – 60

7

Helix

71 – 78

8

Helix

79 – 82

4

Helix

88 – 98

11

Helix

103 – 121

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 28AFB80DA025F8AB	FASTA	824	92,272
	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
	Isoform 2 [UniParc]. Checksum: 45D05E0DBF81DF5B		813	91,081
	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 SKKVEIIIDE LNNLGHPDNK EQTTDQPLAK DKVALLIGNM NYREHPKLKA PLVDVYELTN 370 380 390 400 410 420 LLRQLDFKVV SLLDLTEYEM RNAVDEFLLL LDKGVYGLLY YAGHGYENFG NSFMVPVDAP 430 440 450 460 470 480 NPYRSENCLC VQNILKLMQE KETGLNVFLL DMCRKRNDYD DTIPILDALK VTANIVFGYA 490 500 510 520 530 540 TCQGAEAFEI QHSGLANGIF MKFLKDRLLE DKKITVLLDE VAEDMGKCHL TKGKQALEIR 550 560 570 580 590 600 SSLSEKRALT DPIQGTEYSA ESLVRNLQWA KAHELPESMC LKFDCGVQIQ LGFAAEFSNV 610 620 630 640 650 660 MIIYTSIVYK PPEIIMCDAY VTDFPLDLDI DPKDANKGTP EETGSYLVSK DLPKHCLYTR 670 680 690 700 710 720 LSSLQKLKEH LVFTVCLSYQ YSGLEDTVED KQEVNVGKPL IAKLDMHRGL GRKTCFQTCL 730 740 750 760 770 780 MSNGPYQSSA ATSGGAGHYH SLQDPFHGVY HSHPGNPSNV TPADSCHCSR TPDAFISSFA 790 800 810 HHASCHFSRS NVPVETTDEI PFSFSDRLRI SEK

References

	« Hide 'large scale' referencesShow '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 German cDNA consortium Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases 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: UBIQUITIN LIGASE ACTIVITY.
[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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

T46456.

RefSeq

NP_006776.1.
NP_776216.1.

UniGene

Hs.601217

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2G7R	X-ray	2.70	A/B	25-126	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UDY8.

Protein family/group databases

MEROPS

C14.026.

PTM databases

PhosphoSite

Q9UDY8.

Genome annotation databases

Ensembl

ENSG00000172175. Homo sapiens. [Contig view]

GeneID

10892.

KEGG

hsa:10892.

Organism-specific databases

H-InvDB

HIX0022551.

HGNC

HGNC:6819. MALT1.

HPA

CAB004494.
HPA003865.

MIM

604860. gene.

Orphanet

52417. MALT lymphoma.

PharmGKB

PA30568.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q9UDY8.

HOVERGEN

Q9UDY8.

Gene expression databases

ArrayExpress

Q9UDY8.

CleanEx

HS_MALT1.

GermOnline

ENSG00000172175. Homo sapiens.

Family and domain databases

InterPro

IPR000488. Death.
IPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011600. Pept_C14_cat.
IPR001309. Pept_C14_ICE_p20.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

Pfam

PF00047. ig. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50208. CASPASE_P20. 1 hit.
PS50017. DEATH_DOMAIN. False negative.
PS50835. IG_LIKE. 2 hits.
[Graphical view]

BLOCKS

Search...

ProtoNet

Search...

Other Resources

NextBio

41357.

SOURCE

Search...

Entry information

Entry name

MALT1_HUMAN

Accession

Primary (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:	November 4, 2008
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)