BCL10

BCL10
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MB9
Identifiers
Aliases	BCL10, CARMEN, CIPER, CLAP, c-E10, mE10, IMD37, B-cell CLL/lymphoma 10
External IDs	MGI: 1337994 HomoloGene: 2912 GeneCards: BCL10
Gene ontology Molecular function • transcription coactivator activity • transcription factor binding • protein kinase B binding • NF-kappaB binding • protease binding • protein self-association • kinase binding • protein C-terminus binding • ubiquitin binding • protein binding • kinase activator activity • enzyme binding • protein kinase binding • ubiquitin protein ligase binding • identical protein binding Cellular component • cytoplasm • cytosol • membrane • plasma membrane • T cell receptor complex • protein complex • lipopolysaccharide receptor complex • immunological synapse • perinuclear region of cytoplasm • membrane raft • cytoplasmic microtubule • lysosome • nucleus • CBM complex Biological process • apoptotic process • T cell apoptotic process • regulation of apoptotic process • adaptive immune response • B cell apoptotic process • protein heterooligomerization • regulation of T cell receptor signaling pathway • immune system process • cell death • stimulatory C-type lectin receptor signaling pathway • negative regulation of mature B cell apoptotic process • toll-like receptor signaling pathway • positive regulation of transcription, DNA-templated • Fc-epsilon receptor signaling pathway • cellular defense response • interleukin-6 biosynthetic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • cellular response to mechanical stimulus • neural tube closure • response to fungus • positive regulation of T cell activation • positive regulation of NF-kappaB transcription factor activity • immunoglobulin mediated immune response • protein oligomerization • positive regulation of mast cell cytokine production • response to food • positive regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of interleukin-8 biosynthetic process • positive regulation of extrinsic apoptotic signaling pathway • positive regulation of apoptotic process • lymphotoxin A biosynthetic process • positive regulation of phosphorylation • response to molecule of bacterial origin • I-kappaB kinase/NF-kappaB signaling • positive regulation of protein ubiquitination • T cell receptor signaling pathway • protein homooligomerization • innate immune response Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8915	12042
Ensembl	ENSG00000142867	ENSMUSG00000028191
UniProt	O95999	Q9Z0H7
RefSeq (mRNA)	NM_003921 NM_001320715	NM_009740
RefSeq (protein)	NP_003912.1 NP_001307644.1	NP_033870.1
Location (UCSC)	Chr 1: 85.27 – 85.28 Mb	Chr 3: 145.92 – 145.93 Mb
PubMed search	[1]	[2]
Wikidata

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B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the BCL10 gene.^[3][4] Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma.

Function

This gene was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. This protein is found to form a complex with the paracaspase MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and this protein are thought to synergize in the activation of NF-kappaB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy.^[4] Bcl10 has been shown to be functionally conserved all the way back to zebrafish ^[5]

Interactions

BCL10 has been shown to interact with:

• CARD10,^[6]
• CARD11,^[7]
• CARD14,^[7]
• CARD9^[8]
• CRADD,^[9]
• IKBKG,^[10]
• MALT1,^[11] and
• TRAF2.^[12]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ (March 1999). "Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types". Cell. 96 (1): 35–45. doi:10.1016/S0092-8674(00)80957-5. PMID 9989495.
4. "Entrez Gene: BCL10 B-cell CLL/lymphoma 10".
5. Mazzone P, Scudiero I, Ferravante A, Paolucci M, D'Andrea LE, Varricchio E, Telesio G, De Maio C, Pizzulo M, Zotti T, Reale C, Vito P, Stilo R (April 2015). "Functional characterization of zebrafish (Danio rerio) Bcl10". PLOS ONE. 10 (4): e0122365. doi:10.1371/journal.pone.0122365. PMC 4388727. PMID 25849213.
6. Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J (June 2001). "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B". J. Biol. Chem. 276 (24): 21405–9. doi:10.1074/jbc.M102488200. PMID 11259443.
7. Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES (April 2001). "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877–82. doi:10.1074/jbc.M010512200. PMID 11278692.
8. Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (Dec 2000). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. Biol. Chem. 275 (52): 41082–6. doi:10.1074/jbc.C000726200. PMID 11053425.
9. Lin Q, Liu Y, Moore DJ, Elizer SK, Veach RA, Hawiger J, Ruley HE (2012). "Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes". J. Immunol. 188 (6): 2493–7. doi:10.4049/jimmunol.1101502. PMC 3294148. PMID 22323537.
10. Wu CJ, Ashwell JD (February 2008). "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation". Proc. Natl. Acad. Sci. U.S.A. 105 (8): 3023–8. doi:10.1073/pnas.0712313105. PMC 2268578. PMID 18287044.
11. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (October 2000). "Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma". Mol. Cell. 6 (4): 961–7. doi:10.1016/S1097-2765(05)00086-9. PMID 11090634.
12. Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M (April 2000). "Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein". J. Biol. Chem. 275 (15): 11114–20. doi:10.1074/jbc.275.15.11114. PMID 10753917.

Further reading

• Bertoni F, Cavalli F, Cotter FE, Zucca E (2003). "Genetic alterations underlying the pathogenesis of MALT lymphoma". Hematol. J. 3 (1): 10–3. doi:10.1038/sj/thj/6200146. PMID 11960389.
• Lee WC, Balsara B, Liu Z, Jhanwar SC, Testa JR (1996). "Loss of heterozygosity analysis defines a critical region in chromosome 1p22 commonly deleted in human malignant mesothelioma". Cancer Res. 56 (19): 4297–301. PMID 8813110.
• Koseki T, Inohara N, Chen S, Carrio R, Merino J, Hottiger MO, Nabel GJ, Núñez G (1999). "CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10". J. Biol. Chem. 274 (15): 9955–9961. doi:10.1074/jbc.274.15.9955. PMID 10187770.
• Thome M, Martinon F, Hofmann K, Rubio V, Steiner V, Schneider P, Mattmann C, Tschopp J (1999). "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 (15): 9962–9968. doi:10.1074/jbc.274.15.9962. PMID 10187771.
• Yan M, Lee J, Schilbach S, Goddard A, Dixit V (1999). "mE10, a novel caspase recruitment domain-containing proapoptotic molecule". J. Biol. Chem. 274 (15): 10287–10292. doi:10.1074/jbc.274.15.10287. PMID 10187815.
• Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW (1999). "Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32)". Nat. Genet. 22 (1): 63–68. doi:10.1038/8767. PMID 10319863.
• Srinivasula SM, Ahmad M, Lin JH, Poyet JL, Fernandes-Alnemri T, Tsichlis PN, Alnemri ES (1999). "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 (25): 17946–17954. doi:10.1074/jbc.274.25.17946. PMID 10364242.
• Apostolou S, De Rienzo A, Murthy SS, Jhanwar SC, Testa JR (1999). "Absence of BCL10 mutations in human malignant mesothelioma". Cell. 97 (6): 684–686. doi:10.1016/S0092-8674(02)09765-9. PMID 10380921.
• Costanzo A, Guiet C, Vito P (1999). "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 (29): 20127–20132. doi:10.1074/jbc.274.29.20127. PMID 10400625.
• Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M (2000). "Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein". J. Biol. Chem. 275 (15): 11114–11120. doi:10.1074/jbc.275.15.11114. PMID 10753917.
• Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I, Dyer MJ, Isaacson PG, Du MQ (2000). "BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma". Am. J. Pathol. 157 (4): 1147–1154. doi:10.1016/S0002-9440(10)64630-5. PMC 1850175. PMID 11021819.
• Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (2001). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. Biol. Chem. 275 (52): 41082–41086. doi:10.1074/jbc.C000726200. PMID 11053425.
• Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (2000). "Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma". Mol. Cell. 6 (4): 961–967. doi:10.1016/S1097-2765(05)00086-9. PMID 11090634.
• Poyet JL, Srinivasula SM, Alnemri ES (2001). "vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma". J. Biol. Chem. 276 (5): 3183–3187. doi:10.1074/jbc.C000792200. PMID 11113112.
• Ruland J, Duncan GS, Elia A, del Barco Barrantes I, Nguyen L, Plyte S, Millar DG, Bouchard D, Wakeham A, Ohashi PS, Mak TW (2001). "Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure". Cell. 104 (1): 33–42. doi:10.1016/S0092-8674(01)00189-1. PMID 11163238.
• Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J (2001). "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B". J. Biol. Chem. 276 (24): 21405–21409. doi:10.1074/jbc.M102488200. PMID 11259443.
• Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G (2001). "Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway". J. Biol. Chem. 276 (22): 19012–19019. doi:10.1074/jbc.M009984200. PMID 11262391.
• Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES (2001). "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877–11882. doi:10.1074/jbc.M010512200. PMID 11278692.
• Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J (2001). "Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation". FEBS Lett. 496 (2–3): 121–127. doi:10.1016/S0014-5793(01)02414-0. PMID 11356195.