BCL10 (B-cell CLL/lymphoma 10)

2009-01-01   Pei Lin 

Department of Hematopathology, University of Texas-MD Anderson Cancer Center Houston, Texas, 77030 USA

Identity

HGNC
LOCATION
1p22.3
LOCUSID
ALIAS
CARMEN,CIPER,CLAP,IMD37,c-E10,mE10
FUSION GENES

DNA/RNA

Description

12,308 bases, 4 exons, Transcription: 4.2 kb.

Transcription

Transcription produces 4 alternatively spliced variants and 1 unspliced form with 2,974 bps or 2,819 bps.

Proteins

Description

233 amino acids with a molecular weight of 26252 Da.

Expression

BCL10 is expressed in all normal and malignant tissues. In the lymphoid tissue, it is highly expressed in the germinal center but low in the mantle zone, and intermediate in the marginal zone. BCL10 is likely to play a role in the normal development of the germinal center.

Localisation

BCL10 resides in the cytoplasm or perinuclear region of normal cells.

Function

BCL10 functions normally as a proapoptotic protein through caspase recruitment domain (CARD) at the animo terminal and activation of NF-kappaB pathway. This activity requires oligomerization via the CARD domain and interaction between BCL10 and other CARD domain containing proteins including CARD9, CARD10, CARD11 and CARD14.

Homology

Equine herpesvirus-2 E10 gene.

Implicated in

Entity name
1p rearrangement/Non-Hodgkin lymphoma
Disease
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).
  • Phenotype stem cell origin: Marginal zone B-cells.
  • Epidemiology: Commonly seen in MALT lymphoma involving stomach (approximately 4%) and lung (approximately 9%). Uncommon in MALT lymphoma involving other sites.
  • Evolution: MALT lymphoma may evolve to diffuse large B-cell lymphoma.
  • Prognosis
    Generally indolent.
    Cytogenetics
    In t(1;14)(p22;q32). The gene on 14q32 is IgH. The breakpoint on 1p22 involves a recurrent breakpoint upstream of the promoter of BCL10.
    Hybrid gene
    BCL10-IgH.
    The translocation t(1;14)(p22;q32) is associated with frameshift mutation of BCL10 and truncation of BCL10 protein distal to CARD. The mutant type of BCL10 enhances cell survival and proliferation through activation of NF-kappaB pathway. MALT lymphomas without BCL10 rearrangement may also carry BCL10 mutation however.
    Atlas Image
    MALT lymphoma expressing BCL10 (courtesy of Dr. Du M-Q).
    Fusion protein
    MALT lymphomas with t(1;14)(p22;q32) demonstrate strong nuclear BCL10 staining regardless of BCL10 mutation status. MALT lymphoma without t(1;14)(p22;q32) may also show strong nuclear staining.So a strong nuclear BCL10 staining is not always a presumptive evidence of t(1;14)(p22;q32). This pattern is different from the weak cytoplasmic expression observed in normal germinal center B-cells.
    Oncogenesis
    Loss of CARD domain through translocation and mutations lead to loss of proapoptotic activity. In addition, MALT1 and BCL10 may synergize in the activation of NF-kappaB leading to enhanced cell survival and downstream activation of anti-apoptotic/proliferative signals.
    Entity name
    Various Cancers
    Disease
    BCL10 mutations have also been described in follicular lymphoma, Sezary syndrome, malignant mesothelioma, germ cell tumor, and colon cancer.

    Bibliography

    Pubmed IDLast YearTitleAuthors
    180401432007MALT lymphoma : recent advances in aetiology and molecular genetics.Du MQ et al
    108459242000BCL10 gene mutation in lymphoma.Du MQ et al
    99894951999Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.Willis TG et al
    103198631999Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32).Zhang Q et al

    Other Information

    Locus ID:

    NCBI: 8915
    MIM: 603517
    HGNC: 989
    Ensembl: ENSG00000142867

    Variants:

    dbSNP: 8915
    ClinVar: 8915
    TCGA: ENSG00000142867
    COSMIC: BCL10

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000142867ENST00000620248A0A087WWW9
    ENSG00000142867ENST00000648566O95999
    ENSG00000142867ENST00000649060A0A3B3ISX2

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30

    Pathways

    PathwaySourceExternal ID
    T cell receptor signaling pathwayKEGGko04660
    B cell receptor signaling pathwayKEGGko04662
    T cell receptor signaling pathwayKEGGhsa04660
    B cell receptor signaling pathwayKEGGhsa04662
    TuberculosisKEGGko05152
    TuberculosisKEGGhsa05152
    NF-kappa B signaling pathwayKEGGhsa04064
    NF-kappa B signaling pathwayKEGGko04064
    Metabolism of proteinsREACTOMER-HSA-392499
    Post-translational protein modificationREACTOMER-HSA-597592
    Immune SystemREACTOMER-HSA-168256
    Adaptive Immune SystemREACTOMER-HSA-1280218
    TCR signalingREACTOMER-HSA-202403
    Downstream TCR signalingREACTOMER-HSA-202424
    Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
    Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
    Activation of NF-kappaB in B cellsREACTOMER-HSA-1169091
    Innate Immune SystemREACTOMER-HSA-168249
    Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
    FCERI mediated NF-kB activationREACTOMER-HSA-2871837
    C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
    CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
    Protein ubiquitinationREACTOMER-HSA-8852135
    E3 ubiquitin ligases ubiquitinate target proteinsREACTOMER-HSA-8866654

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    146954752004Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO.167
    191121072009CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex.131
    171019772007CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.81
    182870442008NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation.65
    240749552013Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly.59
    171792152007Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.48
    182527142008Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells.47
    260381142015Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation.42
    172133222007Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10.36
    186257282008The protein kinase C-responsive inhibitory domain of CARD11 functions in NF-kappaB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association.34

    Citation

    Pei Lin

    BCL10 (B-cell CLL/lymphoma 10)

    Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

    Online version: http://atlasgeneticsoncology.org/gene/222/bcl10-(b-cell-cll-lymphoma-10)