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UniProtKB/Swiss-Prot entry O95999


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name BCL10_HUMAN
Primary accession number O95999
Secondary accession numbers None
Integrated into Swiss-Prot on May 2, 2002
Sequence was last modified on May 1, 1999 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 72)
Name and origin of the protein
Protein name B-cell lymphoma/leukemia 10
Synonyms B-cell CLL/lymphoma 10
Bcl-10
CED-3/ICH-1 prodomain homologous E10-like regulator
CIPER
CARD-containing molecule enhancing NF-kappa-B
Cellular homolog of vCARMEN
cCARMEN
Mammalian CARD-containing adapter molecule E10
mE10
Cellular-E10
c-E10
CARD-like apoptotic protein
hCLAP
Gene name
Name: BCL10
Synonyms: CIPER, CLAP
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], VARIANT FOLLICULAR LYMPHOMA GLU-210 DEL, VARIANT MESOTHELIOMA ILE-52, AND VARIANTS GERM CELL TUMOR GLY-58 AND PHE-218.
TISSUE=Lymphoma;
DOI=10.1016/S0092-8674(00)80957-5; PubMed=9989495 [NCBI, ExPASy, EBI, Israel, Japan]
Willis T.G., Jadayel D.M., Du M.-Q., Peng H., Perry A.R., Abdul-Rauf M., Price H., Karran L., Majekodunmi O., Wlodarska I., Pan L., Crook T., Hamoudi R., Isaacson P., Dyer M.J.S.;
"Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.";
Cell 96:35-45(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF LEU-41 AND GLY-78.
DOI=10.1074/jbc.274.15.9955; PubMed=10187770 [NCBI, ExPASy, EBI, Israel, Japan]
Koseki T., Inohara N., Chen S., Carrio R., Merino J., Hottiger M.O., Nabel G.J., Nunez G.;
"CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10.";
J. Biol. Chem. 274:9955-9961(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1074/jbc.274.15.9962; PubMed=10187771 [NCBI, ExPASy, EBI, Israel, Japan]
Thome M., Martinon F., Hofmann K., Rubio V., Steiner V., Schneider P., Mattmann C., Tschopp J.;
"Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase.";
J. Biol. Chem. 274:9962-9968(1999).
[4]
NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF LEU-28; LEU-41; ILE-46; LEU-47; GLU-53 AND ILE-55.
DOI=10.1074/jbc.274.15.10287; PubMed=10187815 [NCBI, ExPASy, EBI, Israel, Japan]
Yan M., Lee J., Schilbach S., Goddard A., Dixit V.M.;
"mE10, a novel caspase recruitment domain-containing proapoptotic molecule.";
J. Biol. Chem. 274:10287-10292(1999).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1074/jbc.274.25.17946; PubMed=10364242 [NCBI, ExPASy, EBI, Israel, Japan]
Srinivasula S.M., Ahmad M., Lin J.-H., Poyet J.-L., Fernandes-Alnemri T., Tsichlis P.N., Alnemri E.S.;
"CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-kappaB activation and apoptosis.";
J. Biol. Chem. 274:17946-17954(1999).
[6]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Spleen;
DOI=10.1074/jbc.274.29.20127; PubMed=10400625 [NCBI, ExPASy, EBI, Israel, Japan]
Costanzo A., Guiet C., Vito P.;
"c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB.";
J. Biol. Chem. 274:20127-20132(1999).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS MALT LYMPHOMA SER-5; GLU-16; GLU-31; ARG-57; LYS-64; GLU-101; PRO-134; ALA-168; SER-174; GLU-213 AND ILE-230.
DOI=10.1038/8767; PubMed=10319863 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Q., Siebert R., Yan M., Hinzmann B., Cui X., Xue L., Rakestraw K.M., Naeve C.W., Beckmann G., Weisenburger D.D., Sanger W.G., Nowotny H., Vesely M., Callet-Bauchu E., Salles G., Dixit V.M., Rosenthal A., Schlegelberger B., Morris S.W.;
"Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32).";
Nat. Genet. 22:63-68(1999).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
PHOSPHORYLATION.
DOI=10.1038/sj.onc.1204576; PubMed=11466612 [NCBI, ExPASy, EBI, Israel, Japan]
Yui D., Yoneda T., Oono K., Katayama T., Imaizumi K., Tohyama M.;
"Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling.";
Oncogene 20:4317-4323(2001).
[10]
FUNCTION, AND MUTAGENESIS OF ARG-228.
DOI=10.1038/ni1568; PubMed=18264101 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The proteolytic activity of the paracaspase MALT1 is key in T cell activation.";
Nat. Immunol. 9:272-281(2008).
[11]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[12]
VARIANTS MESOTHELIOMA SER-5; GLN-45; GLN-58; SER-93; VAL-153; GLU-213 AND PHE-218.
DOI=10.1016/S0092-8674(02)09765-9; PubMed=10380921 [NCBI, ExPASy, EBI, Israel, Japan]
Apostolou S., de Rienzo A., Murthy S.S., Jhanwar S.C., Testa J.R.;
"Absence of BCL10 mutations in human malignant mesothelioma.";
Cell 97:684-686(1999).
Comments
  • FUNCTION: Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1.
  • SUBUNIT: Self-associates by CARD-CARD interaction and forms a tight complex with MALT1. Interacts with other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14. Binds caspase-9 with its C-terminal domain. Interacts with TRAF2 and BIRC2/c-IAP2.
  • INTERACTION:
    P31749:AKT1; NbExp=3; IntAct=EBI-958922, EBI-296087;
    P20749:BCL3; NbExp=2; IntAct=EBI-958922, EBI-958997;
    P62807:HIST1H2BC; NbExp=1; IntAct=EBI-958922, EBI-354552;
    Q14525:KRT33B; NbExp=1; IntAct=EBI-958922, EBI-1049638;
  • SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Note=Appears to have a perinuclear, compact and filamentous pattern of expression. Also found in the nucleus of several types of tumor cells.
  • TISSUE SPECIFICITY: Ubiquitous.
  • PTM: Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2.
  • DISEASE: A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
  • DISEASE: Defects in BCL10 are involved in various types of cancer.
  • SIMILARITY: Contains 1 CARD domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AJ006288; CAA06955.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF057700; AAD15800.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF100338; AAD16428.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF127386; AAD32597.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF134395; AAD39147.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF105066; AAF06894.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF082283; AAC99767.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF097732; AAD24918.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC053617; AAH53617.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00022477; -.
RefSeq NP_003912.1; -.
UniGene Hs.193516
3D structure databases
ModBase O95999.
Protein-protein interaction databases
IntAct O95999; 4.
PTM databases
PhosphoSite O95999; -.
Enzyme and pathway databases
Pathway_Interaction_DB bcr_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.
Reactome REACT_6900; Signaling in Immune system.
Organism-specific databases
GeneCards GC01M085443; -.
H-InvDB HIX0000744; -.
HGNC HGNC:989; BCL10.
GenAtlas BCL10.
HPA CAB001944; -.
MIM 603517; gene. [NCBI / EBI]
Orphanet 52417; MALT lymphoma.
PharmGKB PA25299; -.
Gene expression databases
ArrayExpress O95999; -.
Bgee O95999; -.
CleanEx HS_BCL10; -.
GermOnline ENSG00000142867; Homo sapiens.
Ontologies
GO
GO:0032449; Cellular component: CBM complex (non-traceable author statement from UniProtKB).
GO:0005829; Cellular component: cytosol (inferred from direct assay from UniProtKB).
GO:0005764; Cellular component: lysosome (inferred from direct assay from UniProtKB).
GO:0005634; Cellular component: nucleus (inferred from direct assay from UniProtKB).
GO:0048471; Cellular component: perinuclear region of cytoplasm (inferred from direct assay from UniProtKB).
GO:0051059; Molecular function: NF-kappaB binding (inferred from direct assay from UniProtKB).
GO:0008022; Molecular function: protein C-terminus binding (inferred from physical interaction from UniProtKB).
GO:0043422; Molecular function: protein kinase B binding (inferred from physical interaction from UniProtKB).
GO:0043621; Molecular function: protein self-association (inferred from physical interaction from UniProtKB).
GO:0003713; Molecular function: transcription coactivator activity (inferred from direct assay from UniProtKB).
GO:0043130; Molecular function: ubiquitin binding (inferred from direct assay from UniProtKB).
GO:0031625; Molecular function: ubiquitin protein ligase binding (inferred from physical interaction from UniProtKB).
GO:0006915; Biological process: apoptosis (inferred from direct assay from UniProtKB).
GO:0007049; Biological process: cell cycle (inferred from electronic annotation from UniProtKB-KW).
GO:0045087; Biological process: innate immune response (inferred from expression pattern from UniProtKB).
GO:0042226; Biological process: interleukin-6 biosynthetic process (non-traceable author statement from UniProtKB).
GO:0042109; Biological process: lymphotoxin A biosynthetic process (non-traceable author statement from UniProtKB).
GO:0045786; Biological process: negative regulation of cell cycle (inferred from electronic annotation from UniProtKB-KW).
GO:0002906; Biological process: negative regulation of mature B cell apoptosis (inferred from direct assay from UniProtKB).
GO:0001843; Biological process: neural tube closure (inferred from sequence or structural similarity from UniProtKB).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
GO:0045416; Biological process: positive regulation of interleukin-8 biosynthetic process (inferred from mutant phenotype from UniProtKB).
GO:0032765; Biological process: positive regulation of mast cell cytokine production (non-traceable author statement from UniProtKB).
GO:0051092; Biological process: positive regulation of NF-kappaB transcription factor activity (inferred from direct assay from UniProtKB).
GO:0042327; Biological process: positive regulation of phosphorylation (inferred from direct assay from UniProtKB).
GO:0031398; Biological process: positive regulation of protein ubiquitination (inferred from direct assay from UniProtKB).
GO:0045893; Biological process: positive regulation of transcription, DNA-dependent (inferred from direct assay from UniProtKB).
GO:0051260; Biological process: protein homooligomerization (traceable author statement from UniProtKB).
GO:0002237; Biological process: response to molecule of bacterial origin (inferred from expression pattern from UniProtKB).
GO:0050852; Biological process: T cell receptor signaling pathway (inferred from direct assay from UniProtKB).
GO:0002224; Biological process: toll-like receptor signaling pathway (inferred by curator from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001315; CARD.
IPR011029; DEATH-like.
Graphical view of domain structure.
Gene3D G3DSA:1.10.533.10; DEATH_like; 1.
Pfam PF00619; CARD; 1.
Pfam graphical view of domain structure.
PROSITE PS50209; CARD; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE O95999; -.
Genome annotation databases
Ensembl ENSG00000142867; Homo sapiens. [Contig view]
GeneID 8915; -.
KEGG hsa:8915; -.
Phylogenomic databases
HOGENOM O95999; -.
HOVERGEN O95999; -.
OMA O95999; STVIYHP.
Other
NextBio 33536; -.
SOURCE BCL10; Homo sapiens.
ProtoNet O95999.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Anti-oncogene; Apoptosis; Cell cycle; Chromosomal rearrangement; Cytoplasm; Disease mutation; Phosphoprotein.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   233  233     B-cell lymphoma/leukemia 10. PRO_0000144074
DOMAIN   13   101  89     CARD. 
VARIANT   5     5  1     A -> S (in MALT lymphoma and mesothelioma; dbSNP:rs12037217 [NCBI]). VAR_013208 
VARIANT   16    16  1     V -> E (in MALT lymphoma). VAR_013209 
VARIANT   31    31  1     K -> E (in MALT lymphoma). VAR_013210 
VARIANT   45    45  1     K -> Q (in mesothelioma). VAR_013211 
VARIANT   52    52  1     T -> I (in mesothelioma). VAR_013212 
VARIANT   57    57  1     C -> R (in MALT lymphoma). VAR_013213 
VARIANT   58    58  1     R -> G (in germ cell tumor). VAR_013214 
VARIANT   58    58  1     R -> Q (in mesothelioma). VAR_013215 
VARIANT   64    64  1     R -> K (in MALT lymphoma). VAR_013216 
VARIANT   93    93  1     N -> S (in mesothelioma). VAR_013217 
VARIANT   101   101  1     D -> E (in MALT lymphoma). VAR_013218 
VARIANT   134   134  1     S -> P (in MALT lymphoma). VAR_013219 
VARIANT   153   153  1     M -> V (in mesothelioma). VAR_013220 
VARIANT   168   168  1     T -> A (in MALT lymphoma). VAR_013221 
VARIANT   174   174  1     L -> S (in MALT lymphoma). VAR_013222 
VARIANT   210   210  1     Missing (in follicular lymphoma). VAR_013223
VARIANT   213   213  1     G -> E (in MALT lymphoma and mesothelioma; dbSNP:rs3768235 [NCBI]). VAR_013224 
VARIANT   218   218  1     S -> F (in germ cell tumor, mesothelioma and other cancer cell lines). VAR_013225 
VARIANT   230   230  1     V -> I (in MALT lymphoma). VAR_013226 
MUTAGEN   28    28        L->A: Abolishes cell death-inducing capability. 
MUTAGEN   41    41        L->A: Abolishes cell death-inducing capability. 
MUTAGEN   41    41        L->Q: Abolishes NF-kappa-B activation and homo/hetero-dimerization. 
MUTAGEN   46    46        I->A: Abolishes cell death-inducing capability. 
MUTAGEN   47    47        L->A: Abolishes cell death-inducing capability. 
MUTAGEN   53    53        E->A: Abolishes cell death-inducing capability. 
MUTAGEN   55    55        I->A: Abolishes cell death-inducing capability. 
MUTAGEN   78    78        G->R: Abolishes NF-kappa-B activation. 
MUTAGEN   228   228        R->G: Abolishes MALT1-mediated cleavage. 
MUTAGEN   231   231        S->A: Promotes NF-kappa-B activation. 
Sequence information
Length: 233 AA [This is the length of the unprocessed precursor] Molecular weight: 26252 Da [This is the MW of the unprocessed precursor] CRC64: F87C97F2B784BA4B [This is a checksum on the sequence]
        10         20         30         40         50         60 
MEPTAPSLTE EDLTEVKKDA LENLRVYLCE KIIAERHFDH LRAKKILSRE DTEEISCRTS 

        70         80         90        100        110        120 
SRKRAGKLLD YLQENPKGLD TLVESIRREK TQNFLIQKIT DEVLKLRNIK LEHLKGLKCS 

       130        140        150        160        170        180 
SCEPFPDGAT NNLSRSNSDE SNFSEKLRAS TVMYHPEGES STTPFFSTNS SLNLPVLEVG 

       190        200        210        220        230 
RTENTIFSST TLPRPGDPGA PPLPPDLQLE EEGTCANSSE MFLPLRSRTV SRQ 

O95999 in FASTA format

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