Mouse anti-Human/Mouse/Rat sapiens (Human) BCL10 Monoclonal Antibody

Function

Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation (PubMed:10187770, PubMed:10364242, PubMed:10400625, PubMed:24074955, PubMed:25365219). Acts by channeling adaptive and innate immune signaling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:24074955). Recruited by activated CARD domain-containing proteins: homooligomerized CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex (PubMed:24074955). This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:18287044, PubMed:24074955, PubMed:27777308). Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity (PubMed:26488816). Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR) (PubMed:18264101, PubMed:18287044, PubMed:24074955, PubMed:27777308). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK (PubMed:10187815)

Subcellular Location

Cytoplasm, perinuclear region; Membrane raft

Disease Association

[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] | Immunodeficiency 37 (IMD37) : A form of primary combined immunodeficiency, a group of disorders characterized by severe recurrent infections, with normal numbers or an absence of T and B lymphocytes, and impaired cellular and humoral immunity. IMD37 is characterized by hypogammaglobulinemia without lymphopenia, but with profoundly reduced memory B cells and memory T cells, and increased numbers of circulating naive lymphocytes. Inheritance is autosomal recessive. [The disease is caused by variants affecting the gene represented in this entry] | Lymphoma, mucosa-associated lymphoid type (MALTOMA) : A subtype of non-Hodgkin lymphoma, originating in mucosa-associated lymphoid tissue. MALT lymphomas occur most commonly in the gastro-intestinal tract but have been described in a variety of extranodal sites including the ocular adnexa, salivary gland, thyroid, lung, thymus, and breast. Histologically, they are characterized by an infiltrate of small to medium-sized lymphocytes with abundant cytoplasm and irregularly shaped nuclei. Scattered transformed blasts (large cells) also are present. Non-malignant reactive follicles are observed frequently. A pivotal feature is the presence of lymphoepithelial lesions, with invasion and partial destruction of mucosal glands and crypts by aggregates of tumor cells. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Ubiquitous

Subunit

Homomultimer; homooligomerized following recruitment by CARD domain-containing proteins that form a nucleating helical template that recruits BCL10 via CARD-CARD interaction (PubMed:24074955). Self-associates by CARD-CARD interaction and interacts with other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14 (PubMed:24074955, PubMed:26488816, PubMed:27113748, PubMed:27777308, PubMed:28628108, PubMed:31296852). Forms a complex with CARD14 and MALT1; resulting in the formation of a CBM (CARD14-BCL10-MALT1) complex (PubMed:27113748). Forms a complex with CARD11 and MALT1; resulting in the formation of a CBM (CARD11-BCL10-MALT1) complex (PubMed:24074955, PubMed:28628108). Forms a complex with CARD9 and MALT1; resulting in the formation of a CBM (CARD9-BCL10-MALT1) complex (By similarity). Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Binds caspase-9 with its C-terminal domain (PubMed:10187815). Interacts with TRAF2 and BIRC2/c-IAP2 (PubMed:11466612). Interacts with PELI2 and SOCS3; these interactions may be mutually exclusive (By similarity)

• Willis T.G. et al. Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. — Cell (1999)
• Koseki T. et al. CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. — J. Biol. Chem. (1999)
• Thome M. et al. 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. (1999)
• Yan M. et al. mE10, a novel caspase recruitment domain-containing proapoptotic molecule. — J. Biol. Chem. (1999)
• Srinivasula S.M. et al. CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-kappaB activation and apoptosis. — J. Biol. Chem. (1999)
• Costanzo A. et al. 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. (1999)
• Zhang Q. et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). — Nat. Genet. (1999)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)