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, B cell CLL/lymphoma 10, immune signaling adaptor, BCL10 immune signaling adaptor
External IDs	OMIM: 603517 MGI: 1337994 HomoloGene: 2912 GeneCards: BCL10
Gene location (Human)
Chr.	Chromosome 1 (human)
End	85,276,632 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	145,640,111 bp
RNA expression pattern
	Top expressed in
	oocyte; ; secondary oocyte; ; palpebral conjunctiva; ; germinal epithelium; ; amniotic fluid; ; tibia; ; jejunal mucosa; ; cavity of mouth; ; visceral pleura; ; endothelial cell;
	Top expressed in
	saccule; ; otic placode; ; Paneth cell; ; cumulus cell; ; blood; ; renal corpuscle; ; conjunctival fornix; ; endocardial cushion; ; left colon; ; medial ganglionic eminence;
	More reference expression data
	n/a
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 ; protein binding ; kinase activator activity ; enzyme binding ; protein kinase binding ; ubiquitin protein ligase binding ; identical protein binding ; CARD domain binding ;
Cellular component	cytoplasm ; cytosol ; membrane ; T cell receptor complex ; lipopolysaccharide receptor complex ; immunological synapse ; perinuclear region of cytoplasm ; membrane raft ; cytoplasmic microtubule ; lysosome ; nucleus ; CBM complex ; protein-containing complex ;
Biological process	apoptotic process ; T cell apoptotic process ; regulation of apoptotic process ; adaptive immune response ; B cell apoptotic process ; 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 ; 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 complex oligomerization ; positive regulation of mast cell cytokine production ; response to food ; positive regulation of I-kappaB kinase/NF-kappaB signaling ; positive regulation of extrinsic apoptotic signaling pathway ; 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 ; protein ubiquitination ; positive regulation of apoptotic process ; protein heterooligomerization ; lipopolysaccharide-mediated signaling pathway ; positive regulation of kinase activity ;
	Sources:Amigo / QuickGO
Orthologs
	8915
	12042
	ENSG00000142867
	ENSMUSG00000028191
	O95999
	Q9Z0H7
	NM_003921 ; NM_001320715
	NM_009740
	NP_001307644 ; NP_003912 ; NP_001307644.1
	NP_033870
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 27, 2024

B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the BCL10 gene.^[5]^[6] Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma.

Function

Bcl10 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 activate NF-κB. This protein is reported to interact with other CARD and coiled coil domain containing proteins including CARD9, -10, -11 and -14, which are thought to function as upstream regulators in NF-κB 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 Bcl10 thought to synergize in the activation of NF-κB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy.^[6] Bcl10 is evolutionary conserved since cnidaria and has been shown to be functionally conserved all the way back to zebrafish.^[7]^[8] Notably, just like the upstream CARD-CC family, Bcl10 is absent in insects and nematodes, and the correlated phylogenetic distribution of Bcl10 and CARD-CC proteins indicate a conserved complex.

Interactions

BCL10 has been shown to interact with:

Related Research Articles

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Caspase recruitment domain-containing protein 14, also known as D-containing MAGUK protein 2, is a protein in the CARD-CC protein family that in humans is encoded by the CARD14 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000142867 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028191 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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. S2CID 1613152.
1 2 "Entrez Gene: BCL10 B-cell CLL/lymphoma 10".
↑ 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. Bibcode:2015PLoSO..1022365M. doi: 10.1371/journal.pone.0122365 . PMC 4388727 . PMID 25849213.
↑ Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi: 10.3389/fimmu.2018.01136 . PMC 5978004 . PMID 29881386.
↑ 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.
1 2 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. S2CID 35815019.
↑ 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.
↑ 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.
↑ 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. Bibcode:2008PNAS..105.3023W. doi: 10.1073/pnas.0712313105 . PMC 2268578 . PMID 18287044.
↑ 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.
↑ 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.

External links

Human BCL10 genome location and BCL10 gene details page in the UCSC Genome Browser .

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. S2CID 1858018.
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. S2CID 9100379.
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. S2CID 35815019.
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. S2CID 22024213.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000142867 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028191 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9989495-5] 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. S2CID 1613152.

[entrez-6] 1 2 "Entrez Gene: BCL10 B-cell CLL/lymphoma 10".

[pmid25849213-7] 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. Bibcode:2015PLoSO..1022365M. doi: 10.1371/journal.pone.0122365 . PMC 4388727 . PMID 25849213.

[8] Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi: 10.3389/fimmu.2018.01136 . PMC 5978004 . PMID 29881386.

[pmid11259443-9] 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.

[pmid11278692-10] 1 2 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. S2CID 35815019.

[pmid11053425-11] 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.

[pmid22323537-12] 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.

[pmid18287044-13] 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. Bibcode:2008PNAS..105.3023W. doi: 10.1073/pnas.0712313105 . PMC 2268578 . PMID 18287044.

[pmid11090634-14] 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.

[pmid10753917-15] 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.

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