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Protein

B-cell lymphoma/leukemia 10

Gene

BCL10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in adaptive immune response (PubMed:25365219). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1 (PubMed:18264101).2 Publications

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • kinase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • protease binding Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • protein kinase B binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein self-association Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • B cell apoptotic process Source: Ensembl
  • cell death Source: UniProtKB
  • cellular defense response Source: Ensembl
  • cellular response to mechanical stimulus Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • immunoglobulin mediated immune response Source: Ensembl
  • innate immune response Source: UniProtKB
  • interleukin-6 biosynthetic process Source: UniProtKB
  • lymphotoxin A biosynthetic process 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: Ensembl
  • positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-8 biosynthetic process Source: UniProtKB
  • positive regulation of mast cell cytokine production Source: UniProtKB
  • 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 heterooligomerization Source: Ensembl
  • protein homooligomerization Source: UniProtKB
  • protein oligomerization 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
  • response to molecule of bacterial origin Source: UniProtKB
  • 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

Keywordsi

Biological processApoptosis, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-8866654. E3 ubiquitin ligases ubiquitinate target proteins.
SignaLinkiO95999.
SIGNORiO95999.

Names & Taxonomyi

Protein namesi
Recommended name:
B-cell lymphoma/leukemia 10
Alternative name(s):
B-cell CLL/lymphoma 10
Short name:
Bcl-10
CARD-containing molecule enhancing NF-kappa-B
CARD-like apoptotic protein
Short name:
hCLAP
CED-3/ICH-1 prodomain homologous E10-like regulator
Short name:
CIPER
Cellular homolog of vCARMEN
Short name:
cCARMEN
Cellular-E10
Short name:
c-E10
Mammalian CARD-containing adapter molecule E10
Short name:
mE10
Gene namesi
Name:BCL10
Synonyms:CIPER, CLAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000142867.12.
HGNCiHGNC:989. BCL10.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

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)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:616098
Lymphoma, mucosa-associated lymphoid type (MALTOMA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:137245

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28L → A: Abolishes cell death-inducing capability. 1 Publication1
Mutagenesisi41L → A: Abolishes cell death-inducing capability. 2 Publications1
Mutagenesisi41L → Q: Abolishes NF-kappa-B activation and homo/hetero-dimerization. 2 Publications1
Mutagenesisi46I → A: Abolishes cell death-inducing capability. 1 Publication1
Mutagenesisi47L → A: Abolishes cell death-inducing capability. 1 Publication1
Mutagenesisi53E → A: Abolishes cell death-inducing capability. 1 Publication1
Mutagenesisi55I → A: Abolishes cell death-inducing capability. 1 Publication1
Mutagenesisi78G → R: Abolishes NF-kappa-B activation. 1 Publication1
Mutagenesisi81 – 85TLVES → ALVEA: Complete loss of IKBKB/IKKB-mediated phosphorylation. 1 Publication5
Mutagenesisi228R → G: Abolishes MALT1-mediated cleavage. 1 Publication1
Mutagenesisi231S → A: Promotes NF-kappa-B activation. 1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi8915.
MalaCardsiBCL10.
MIMi137245. phenotype.
616098. phenotype.
OpenTargetsiENSG00000142867.
PharmGKBiPA25299.

Polymorphism and mutation databases

BioMutaiBCL10.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440741 – 233B-cell lymphoma/leukemia 10Add BLAST233

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei138PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2. Phosphorylated by IKBKB/IKKB.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO95999.
PaxDbiO95999.
PeptideAtlasiO95999.
PRIDEiO95999.

PTM databases

iPTMnetiO95999.
PhosphoSitePlusiO95999.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000142867.
CleanExiHS_BCL10.
ExpressionAtlasiO95999. baseline and differential.
GenevisibleiO95999. HS.

Organism-specific databases

HPAiCAB001944.
HPA017925.

Interactioni

Subunit structurei

Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Self-associates by CARD-CARD interaction and forms a tight complex with MALT1. Interacts with other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14. Forms a complex with CARD14 and MALT1; resulting in the formation of a CBM (CARD14-BCL10-MALT1) complex (PubMed:27113748). Binds caspase-9 with its C-terminal domain. Interacts with TRAF2 and BIRC2/c-IAP2. Interacts with PELI2 and SOCS3; these interactions may be mutually exclusive (By similarity). Interacts with CARD11 and MALT1; as part of a CBM (CARD11-BCL10-MALT1) complex involved in NF-kappa-B activation.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • kinase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • protease binding Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • protein kinase B binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein self-association Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114429. 65 interactors.
CORUMiO95999.
DIPiDIP-29740N.
IntActiO95999. 39 interactors.
MINTiMINT-89139.
STRINGi9606.ENSP00000271015.

Structurei

Secondary structure

1233
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 14Combined sources4
Helixi17 – 28Combined sources12
Turni29 – 31Combined sources3
Beta strandi32 – 38Combined sources7
Helixi39 – 42Combined sources4
Helixi49 – 53Combined sources5
Turni54 – 57Combined sources4
Helixi61 – 72Combined sources12
Turni76 – 79Combined sources4
Helixi80 – 86Combined sources7
Beta strandi89 – 92Combined sources4
Helixi94 – 105Combined sources12
Helixi107 – 113Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MB9NMR-A1-115[»]
ProteinModelPortaliO95999.
SMRiO95999.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 101CARDPROSITE-ProRule annotationAdd BLAST89

Phylogenomic databases

eggNOGiENOG410IVMM. Eukaryota.
ENOG4111JRA. LUCA.
GeneTreeiENSGT00490000043442.
HOGENOMiHOG000008671.
HOVERGENiHBG050680.
InParanoidiO95999.
KOiK07368.
OMAiRHYLCDK.
OrthoDBiEOG091G0UTQ.
PhylomeDBiO95999.
TreeFamiTF328636.

Family and domain databases

InterProiView protein in InterPro
IPR033238. BCL10/E10.
IPR001315. CARD.
IPR011029. DEATH-like_dom_sf.
PANTHERiPTHR34920. PTHR34920. 1 hit.
PfamiView protein in Pfam
PF00619. CARD. 1 hit.
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiView protein in PROSITE
PS50209. CARD. 1 hit.

Sequencei

Sequence statusi: Complete.

O95999-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPTAPSLTE EDLTEVKKDA LENLRVYLCE KIIAERHFDH LRAKKILSRE
60 70 80 90 100
DTEEISCRTS SRKRAGKLLD YLQENPKGLD TLVESIRREK TQNFLIQKIT
110 120 130 140 150
DEVLKLRNIK LEHLKGLKCS SCEPFPDGAT NNLSRSNSDE SNFSEKLRAS
160 170 180 190 200
TVMYHPEGES STTPFFSTNS SLNLPVLEVG RTENTIFSST TLPRPGDPGA
210 220 230
PPLPPDLQLE EEGTCANSSE MFLPLRSRTV SRQ
Length:233
Mass (Da):26,252
Last modified:May 1, 1999 - v1
Checksum:iF87C97F2B784BA4B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0132085A → S Found in a MALT lymphoma sample; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs12037217Ensembl.1
Natural variantiVAR_01320916V → E Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_01321031K → E Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_01321145K → Q1 Publication1
Natural variantiVAR_01321252T → I Found in a mesothelioma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_01321357C → R Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_01321458R → G Found in a germ cell tumor sample; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121918314Ensembl.1
Natural variantiVAR_01321558R → Q1 Publication1
Natural variantiVAR_01321664R → K Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_01321793N → S1 Publication1
Natural variantiVAR_013218101D → E Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_013219134S → P Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_013220153M → V1 Publication1
Natural variantiVAR_077898162T → M Found in a testicular teratoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs200837308Ensembl.1
Natural variantiVAR_013221168T → A Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_013222174L → S Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_013223210Missing Found in a follicular lymphoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_013224213G → E Found in a MALT lymphoma sample; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs3768235Ensembl.1
Natural variantiVAR_013225218S → F Found in a germ cell tumor and other cancer cell lines; unknown pathological significance. 2 Publications1
Natural variantiVAR_013226230V → I Found in a MALT lymphoma sample; unknown pathological significance. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006288 mRNA. Translation: CAA06955.1.
AF057700 mRNA. Translation: AAD15800.1.
AF100338 mRNA. Translation: AAD16428.1.
AF127386 mRNA. Translation: AAD32597.1.
AF134395 mRNA. Translation: AAD39147.1.
AF105066 mRNA. Translation: AAF06894.1.
AF082283 mRNA. Translation: AAC99767.1.
AF097732 Genomic DNA. Translation: AAD24918.1.
AK291346 mRNA. Translation: BAF84035.1.
AL590113 Genomic DNA. No translation available.
CH471097 Genomic DNA. Translation: EAW73208.1.
BC053617 mRNA. Translation: AAH53617.1.
CCDSiCCDS704.1.
RefSeqiNP_003912.1. NM_003921.4.
UniGeneiHs.193516.

Genome annotation databases

EnsembliENST00000370580; ENSP00000359612; ENSG00000142867.
GeneIDi8915.
KEGGihsa:8915.
UCSCiuc021opd.3. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiBCL10_HUMAN
AccessioniPrimary (citable) accession number: O95999
Secondary accession number(s): Q5VUF1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 1, 1999
Last modified: November 22, 2017
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references