O95999 (BCL10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
B-cell lymphoma/leukemia 10

Alternative name(s):
B-cell CLL/lymphoma 10
Short name=Bcl-10
CARD-containing molecule enhancing NF-kappa-B
CARD-like apoptotic protein
Short name=hCLAP
CED-3/ICH-1 prodomain homologous E10-like regulator
Short name=CIPER
Cellular homolog of vCARMEN
Short name=cCARMEN
Cellular-E10
Short name=c-E10
Mammalian CARD-containing adapter molecule E10
Short name=mE10

Gene names

Name:	BCL10
Synonyms:	CIPER, CLAP

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	233 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (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. Ref.12
Subunit structure	Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. 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.
Subcellular location	Cytoplasm › perinuclear region. Membrane raft. Note: Appears to have a perinuclear, compact and filamentous pattern of expression. Also found in the nucleus of several types of tumor cells. Colocalized with DPP4 in membrane rafts. Ref.10
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2. Phosphorylated by IKBKB/IKKB. Ref.9 Ref.11
Involvement in disease	Note=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. Note=Defects in BCL10 are involved in various types of cancer. Defects in BCL10 are a cause of mesothelioma malignant (MESOM) [MIM:156240]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.
Sequence similarities	Contains 1 CARD domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Chromosomal rearrangement
Disease	Disease mutation Tumor suppressor
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell receptor signaling pathway Inferred from direct assay. Source: UniProtKB apoptotic process Inferred from direct assay Ref.9. Source: UniProtKB cellular response to mechanical stimulus Inferred from expression pattern. Source: UniProtKB innate immune response Inferred from expression pattern. Source: UniProtKB interleukin-6 biosynthetic process Non-traceable author statement. Source: UniProtKB lymphotoxin A biosynthetic process Non-traceable author statement. Source: UniProtKB negative regulation of mature B cell apoptosis Inferred from direct assay. Source: UniProtKB neural tube closure Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of interleukin-8 biosynthetic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of mast cell cytokine production Non-traceable author statement. Source: UniProtKB positive regulation of phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of protein ubiquitination Inferred from direct assay. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB protein homooligomerization Inferred from sequence or structural similarity. Source: UniProtKB response to molecule of bacterial origin Inferred from expression pattern. Source: UniProtKB toll-like receptor signaling pathway Inferred by curator. Source: UniProtKB
Cellular component	CBM complex Non-traceable author statement. Source: UniProtKB cytosol Inferred from direct assay. Source: UniProtKB lysosome Inferred from direct assay. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	NF-kappaB binding Inferred from direct assay. Source: UniProtKB protease binding Inferred from physical interaction. Source: BHF-UCL protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase B binding Inferred from physical interaction. Source: UniProtKB protein self-association Inferred from physical interaction. Source: UniProtKB transcription coactivator activity Inferred from direct assay. Source: UniProtKB ubiquitin binding Inferred from direct assay. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKT1	P31749	4	EBI-958922,EBI-296087
BCL3	P20749	3	EBI-958922,EBI-958997

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 233	233	B-cell lymphoma/leukemia 10		PRO_0000144074
Regions
	Domain	13 – 101	89	CARD
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.13
Natural variations
	Natural variant	5	1	A → S in MALT lymphoma and mesothelioma. Ref.7 Ref.15 Corresponds to variant rs12037217 [ dbSNP | Ensembl ].		VAR_013208
	Natural variant	16	1	V → E in MALT lymphoma. Ref.7		VAR_013209
	Natural variant	31	1	K → E in MALT lymphoma. Ref.7		VAR_013210
	Natural variant	45	1	K → Q in mesothelioma. Ref.15		VAR_013211
	Natural variant	52	1	T → I in mesothelioma. Ref.1		VAR_013212
	Natural variant	57	1	C → R in MALT lymphoma. Ref.7		VAR_013213
	Natural variant	58	1	R → G in germ cell tumor. Ref.1		VAR_013214
	Natural variant	58	1	R → Q in mesothelioma. Ref.15		VAR_013215
	Natural variant	64	1	R → K in MALT lymphoma. Ref.7		VAR_013216
	Natural variant	93	1	N → S in mesothelioma. Ref.15		VAR_013217
	Natural variant	101	1	D → E in MALT lymphoma. Ref.7		VAR_013218
	Natural variant	134	1	S → P in MALT lymphoma. Ref.7		VAR_013219
	Natural variant	153	1	M → V in mesothelioma. Ref.15		VAR_013220
	Natural variant	168	1	T → A in MALT lymphoma. Ref.7		VAR_013221
	Natural variant	174	1	L → S in MALT lymphoma. Ref.7		VAR_013222
	Natural variant	210	1	Missing in follicular lymphoma.		VAR_013223
	Natural variant	213	1	G → E in MALT lymphoma and mesothelioma. Ref.7 Ref.15 Corresponds to variant rs3768235 [ dbSNP | Ensembl ].		VAR_013224
	Natural variant	218	1	S → F in germ cell tumor, mesothelioma and other cancer cell lines. Ref.1 Ref.15		VAR_013225
	Natural variant	230	1	V → I in MALT lymphoma. Ref.7		VAR_013226
Experimental info
	Mutagenesis	28	1	L → A: Abolishes cell death-inducing capability. Ref.4
	Mutagenesis	41	1	L → A: Abolishes cell death-inducing capability. Ref.2 Ref.4
	Mutagenesis	41	1	L → Q: Abolishes NF-kappa-B activation and homo/hetero-dimerization. Ref.2 Ref.4
	Mutagenesis	46	1	I → A: Abolishes cell death-inducing capability. Ref.4
	Mutagenesis	47	1	L → A: Abolishes cell death-inducing capability. Ref.4
	Mutagenesis	53	1	E → A: Abolishes cell death-inducing capability. Ref.4
	Mutagenesis	55	1	I → A: Abolishes cell death-inducing capability. Ref.4
	Mutagenesis	78	1	G → R: Abolishes NF-kappa-B activation. Ref.2
	Mutagenesis	81 – 85	5	TLVES → ALVEA: Complete loss of IKBKB/IKKB-mediated phosphorylation. Ref.11
	Mutagenesis	228	1	R → G: Abolishes MALT1-mediated cleavage. Ref.12
	Mutagenesis	231	1	S → A: Promotes NF-kappa-B activation.

Sequences

	Sequence		Length	Mass (Da)
	O95999 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: F87C97F2B784BA4B	FASTA	233	26,252
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types." 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. Cell 96:35-45(1999) [PubMed: 9989495] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT FOLLICULAR LYMPHOMA GLU-210 DEL, VARIANT MESOTHELIOMA ILE-52, VARIANTS GERM CELL TUMOR GLY-58 AND PHE-218. Tissue: Lymphoma.
[2]	"CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10." Koseki T., Inohara N., Chen S., Carrio R., Merino J., Hottiger M.O., Nabel G.J., Nunez G. J. Biol. Chem. 274:9955-9961(1999) [PubMed: 10187770] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LEU-41 AND GLY-78.
[3]	"Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase." Thome M., Martinon F., Hofmann K., Rubio V., Steiner V., Schneider P., Mattmann C., Tschopp J. J. Biol. Chem. 274:9962-9968(1999) [PubMed: 10187771] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"mE10, a novel caspase recruitment domain-containing proapoptotic molecule." Yan M., Lee J., Schilbach S., Goddard A., Dixit V.M. J. Biol. Chem. 274:10287-10292(1999) [PubMed: 10187815] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LEU-28; LEU-41; ILE-46; LEU-47; GLU-53 AND ILE-55.
[5]	"CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-kappaB activation and apoptosis." Srinivasula S.M., Ahmad M., Lin J.-H., Poyet J.-L., Fernandes-Alnemri T., Tsichlis P.N., Alnemri E.S. J. Biol. Chem. 274:17946-17954(1999) [PubMed: 10364242] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB." Costanzo A., Guiet C., Vito P. J. Biol. Chem. 274:20127-20132(1999) [PubMed: 10400625] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[7]	"Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32)." 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. Nat. Genet. 22:63-68(1999) [PubMed: 10319863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], 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.
[8]	"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]. Tissue: Eye.
[9]	"Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling." Yui D., Yoneda T., Oono K., Katayama T., Imaizumi K., Tohyama M. Oncogene 20:4317-4323(2001) [PubMed: 11466612] [Abstract] Cited for: PHOSPHORYLATION.
[10]	"Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1." Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C. J. Biol. Chem. 282:10117-10131(2007) [PubMed: 17287217] [Abstract] Cited for: IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, SUBCELLULAR LOCATION.
[11]	"Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10." Lobry C., Lopez T., Israel A., Weil R. Proc. Natl. Acad. Sci. U.S.A. 104:908-913(2007) [PubMed: 17213322] [Abstract] Cited for: PHOSPHORYLATION BY IKBKB/IKKB, MUTAGENESIS OF 81-THR--SER-85.
[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, MUTAGENESIS OF ARG-228.
[13]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Absence of BCL10 mutations in human malignant mesothelioma." Apostolou S., de Rienzo A., Murthy S.S., Jhanwar S.C., Testa J.R. Cell 97:684-686(1999) [PubMed: 10380921] [Abstract] Cited for: VARIANTS MESOTHELIOMA SER-5; GLN-45; GLN-58; SER-93; VAL-153; GLU-213 AND PHE-218.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ006288 mRNA. Translation: CAA06955.1. AF057700 mRNA. Translation: AAD15800.1. AF100338 mRNA. Translation: AAD16428.1. AF127386 mRNA. Translation: AAD32597.1. AF134395 mRNA. Translation: AAD39147.1. AF105066 mRNA. Translation: AAF06894.1. AF082283 mRNA. Translation: AAC99767.1. AF097732 Genomic DNA. Translation: AAD24918.1. BC053617 mRNA. Translation: AAH53617.1.
IPI	IPI00022477.
RefSeq	NP_003912.1. NM_003921.4.
UniGene	Hs.193516.
3D structure databases
ProteinModelPortal	O95999.
SMR	O95999. Positions 13-99.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29740N.
IntAct	O95999. 9 interactions.
MINT	MINT-89139.
STRING	O95999.
PTM databases
PhosphoSite	O95999.
Proteomic databases
PRIDE	O95999.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000271015; ENSP00000271015; ENSG00000142867. ENST00000370580; ENSP00000359612; ENSG00000142867. ENST00000394761; ENSP00000378242; ENSG00000142867.
GeneID	8915.
KEGG	hsa:8915.
UCSC	uc001dkz.1. human.
Organism-specific databases
CTD	8915.
GeneCards	GC01M085731.
H-InvDB	HIX0000744.
HGNC	HGNC:989. BCL10.
HPA	CAB001944. HPA017925.
MIM	156240. phenotype. 603517. gene.
neXtProt	NX_O95999.
PharmGKB	PA25299.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG716968.
HOVERGEN	HBG050680.
InParanoid	O95999.
OMA	ASTVIYH.
OrthoDB	EOG41JZD7.
PhylomeDB	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. Immune System.
Gene expression databases
ArrayExpress	O95999.
Bgee	O95999.
CleanEx	HS_BCL10.
Genevestigator	O95999.
GermOnline	ENSG00000142867. Homo sapiens.
Family and domain databases
InterPro	IPR001315. CARD. IPR011029. DEATH-like. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
KO	K07368.
Pfam	PF00619. CARD. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33536.
SOURCE	Search...

Entry information

Entry name

BCL10_HUMAN

Accession

Primary (citable) accession number: O95999

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.