BCL10

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 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

B Cell CLL/Lymphoma 10

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:25365219, PubMed:24074955).
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:27777308, PubMed:24074955).
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:27777308, PubMed:24074955).
Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK (PubMed:10187815).

Adaptive immune response Source: UniProtKB
B cell apoptotic process Source: Ensembl
Cell death Source: UniProtKB
Cellular defense response Source: Ensembl
Cellular response to lipopolysaccharide Source: UniProtKB
Cellular response to mechanical stimulus Source: UniProtKB
Fc-epsilon receptor signaling pathway Source: Reactome
I-kappaB kinase/NF-kappaB signaling Source: GO_Central
Immunoglobulin mediated immune response Source: Ensembl
Innate immune response Source: UniProtKB
Lipopolysaccharide-mediated signaling pathway Source: UniProtKB
Negative regulation of mature B cell apoptotic process Source: UniProtKB
Neural tube closure Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
Positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of interleukin-6 production Source: GO_Central
Positive regulation of interleukin-8 production Source: UniProtKB
Positive regulation of kinase activity Source: GOC
Positive regulation of lymphotoxin A production Source: GO_Central
Positive regulation of mast cell cytokine production Source: GO_Central
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of phosphorylation Source: UniProtKB
Positive regulation of protein ubiquitination Source: UniProtKB
Positive regulation of T cell activation Source: Ensembl
Positive regulation of transcription, DNA-templated Source: UniProtKB
Protein ubiquitination Source: Reactome
Regulation of T cell receptor signaling pathway Source: Ensembl
Response to food Source: UniProtKB
Response to fungus Source: Ensembl
Stimulatory C-type lectin receptor signaling pathway Source: Reactome
T cell apoptotic process Source: Ensembl
T cell receptor signaling pathway Source: UniProtKB
Toll-like receptor signaling pathway Source: UniProtKB

Perinuclear region; Membrane raft. 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.

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.
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.

Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2 (PubMed:11466612). Phosphorylated by IKBKB/IKKB (PubMed:17213322).
Ubiquitinated via both 'Lys-63'-linked and linear ('Met-1'-linked) polyubiquitin chains in response to T-cell receptor (TCR) activation (PubMed:18287044, PubMed:27777308). Ubiquitination is recognized by IKBKG/NEMO, the regulatory subunit of I-kappa-B kinase (IKK), and is required for TCR-induced NF-kappa-B activation (PubMed:18287044, PubMed:27777308). Linear ubiquitination at Lys-17, Lys-31 and Lys-63 is mediated by RNF31/HOIP; linear ubiquitination is recognized with much higher affinity than 'Lys-63'-linked ubiquitin by IKBKG/NEMO (PubMed:27777308). CARD11 is required for linear ubiquitination by HOIP by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308).
Proteolytically cleaved by MALT1; required for T-cell activation.