ID BCL3_HUMAN Reviewed; 454 AA.
AC P20749;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 2.
DT 27-MAR-2024, entry version 214.
DE RecName: Full=B-cell lymphoma 3 protein;
DE Short=BCL-3;
DE AltName: Full=Proto-oncogene BCL3;
GN Name=BCL3; Synonyms=BCL4, D19S37;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND CHROMOSOMAL TRANSLOCATION.
RX PubMed=2180580; DOI=10.1016/0092-8674(90)90347-h;
RA Ohno H., Takimoto G., McKeithan T.W.;
RT "The candidate proto-oncogene bcl-3 is related to genes implicated in cell
RT lineage determination and cell cycle control.";
RL Cell 60:991-997(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 87-454, AND CHROMOSOMAL TRANSLOCATION.
RC TISSUE=Leukemia;
RX PubMed=7896265; DOI=10.1006/geno.1994.1588;
RA McKeithan T.W., Ohno H., Dickstein J., Hume E.;
RT "Genomic structure of the candidate proto-oncogene BCL3.";
RL Genomics 24:120-126(1994).
RN [4]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH NFKB2/P52.
RX PubMed=8453667; DOI=10.1016/0092-8674(93)90401-b;
RA Bours V., Franzoso G., Azarenko V., Park S., Kanno T., Brown K.,
RA Siebenlist U.;
RT "The oncoprotein Bcl-3 directly transactivates through kappa B motifs via
RT association with DNA-binding p50B homodimers.";
RL Cell 72:729-739(1993).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH NFKB1/P50.
RX PubMed=10469655; DOI=10.1093/emboj/18.17.4766;
RA Heissmeyer V., Krappmann D., Wulczyn F.G., Scheidereit C.;
RT "NF-kappaB p105 is a target of IkappaB kinases and controls signal
RT induction of Bcl-3-p50 complexes.";
RL EMBO J. 18:4766-4778(1999).
RN [6]
RP INTERACTION WITH COPS5 AND PIR.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., Wulczyn F.G.,
RA Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and
RT nuclear co-regulators.";
RL Oncogene 18:3316-3323(1999).
RN [7]
RP INTERACTION WITH N4BP2.
RX PubMed=12730195; DOI=10.1074/jbc.m303518200;
RA Watanabe N., Wachi S., Fujita T.;
RT "Identification and characterization of BCL-3-binding protein: implications
RT for transcription and DNA repair or recombination.";
RL J. Biol. Chem. 278:26102-26110(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-374, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 127-367.
RX PubMed=11707390; DOI=10.1093/emboj/20.22.6180;
RA Michel F., Soler-Lopez M., Petosa C., Cramer P., Siebenlist U.,
RA Muller C.W.;
RT "Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member
RT of the IkappaB protein family.";
RL EMBO J. 20:6180-6190(2001).
RN [10]
RP PHOSPHORYLATION AT SER-402 AND SER-406.
RX PubMed=15469820; DOI=10.1016/j.molcel.2004.09.004;
RA Viatour P., Dejardin E., Warnier M., Lair F., Claudio E., Bureau F.,
RA Marine J.C., Merville M.P., Maurer U., Green D., Piette J., Siebenlist U.,
RA Bours V., Chariot A.;
RT "GSK3-mediated BCL-3 phosphorylation modulates its degradation and its
RT oncogenicity.";
RL Mol. Cell 16:35-45(2004).
CC -!- FUNCTION: Contributes to the regulation of transcriptional activation
CC of NF-kappa-B target genes. In the cytoplasm, inhibits the nuclear
CC translocation of the NF-kappa-B p50 subunit. In the nucleus, acts as
CC transcriptional activator that promotes transcription of NF-kappa-B
CC target genes. Contributes to the regulation of cell proliferation (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:8453667}.
CC -!- SUBUNIT: Component of a complex consisting of the NF-kappa-B p52-p52
CC homodimer and BCL3. Component of a complex consisting of the NF-kappa-B
CC p50-p50 homodimer and BCL3. Interacts with N4BP2, COPS5 and PIR.
CC Interacts with CYLD (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P20749; O95999: BCL10; NbExp=3; IntAct=EBI-958997, EBI-958922;
CC P20749; P56545: CTBP2; NbExp=2; IntAct=EBI-958997, EBI-741533;
CC P20749; P06239: LCK; NbExp=3; IntAct=EBI-958997, EBI-1348;
CC P20749; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-958997, EBI-2811583;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Cytoplasm,
CC perinuclear region {ECO:0000250}. Note=Ubiquitination via 'Lys-63'-
CC linked ubiquitin chains is required for nuclear accumulation.
CC {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. Ubiquitination via 'Lys-63'-linked ubiquitin
CC chains is required for nuclear accumulation. Deubiquitinated by CYLD,
CC which acts on 'Lys-63'-linked ubiquitin chains. Deubiquitination by
CC CYLD prevents nuclear accumulation (By similarity). {ECO:0000250}.
CC -!- PTM: Activated by phosphorylation. {ECO:0000269|PubMed:15469820}.
CC -!- DISEASE: Note=A chromosomal aberration involving BCL3 may be a cause of
CC B-cell chronic lymphocytic leukemia (B-CLL). Translocation
CC t(14;19)(q32;q13.1) with immunoglobulin gene regions.
CC {ECO:0000269|PubMed:2180580, ECO:0000269|PubMed:7896265}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA51815.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA51816.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH64993.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M31731; AAA51816.1; ALT_INIT; Genomic_DNA.
DR EMBL; M31732; AAA51815.1; ALT_INIT; mRNA.
DR EMBL; AC092066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064993; AAH64993.1; ALT_INIT; mRNA.
DR EMBL; AH006679; AAC51348.1; -; Genomic_DNA.
DR CCDS; CCDS12642.2; -.
DR PIR; A34794; A34794.
DR RefSeq; NP_005169.2; NM_005178.4.
DR PDB; 1K1A; X-ray; 1.86 A; A=127-367.
DR PDB; 1K1B; X-ray; 1.90 A; A=127-367.
DR PDBsum; 1K1A; -.
DR PDBsum; 1K1B; -.
DR AlphaFoldDB; P20749; -.
DR SMR; P20749; -.
DR BioGRID; 107074; 49.
DR CORUM; P20749; -.
DR IntAct; P20749; 12.
DR MINT; P20749; -.
DR STRING; 9606.ENSP00000164227; -.
DR ChEMBL; CHEMBL4523197; -.
DR GuidetoPHARMACOLOGY; 3232; -.
DR iPTMnet; P20749; -.
DR PhosphoSitePlus; P20749; -.
DR BioMuta; BCL3; -.
DR DMDM; 294862410; -.
DR EPD; P20749; -.
DR jPOST; P20749; -.
DR MassIVE; P20749; -.
DR MaxQB; P20749; -.
DR PaxDb; 9606-ENSP00000164227; -.
DR PeptideAtlas; P20749; -.
DR ProteomicsDB; 53783; -.
DR Pumba; P20749; -.
DR Antibodypedia; 3672; 418 antibodies from 41 providers.
DR DNASU; 602; -.
DR Ensembl; ENST00000164227.10; ENSP00000164227.5; ENSG00000069399.15.
DR GeneID; 602; -.
DR KEGG; hsa:602; -.
DR MANE-Select; ENST00000164227.10; ENSP00000164227.5; NM_005178.5; NP_005169.2.
DR UCSC; uc010xxe.3; human.
DR AGR; HGNC:998; -.
DR DisGeNET; 602; -.
DR GeneCards; BCL3; -.
DR HGNC; HGNC:998; BCL3.
DR HPA; ENSG00000069399; Tissue enhanced (liver).
DR MIM; 109560; gene.
DR neXtProt; NX_P20749; -.
DR OpenTargets; ENSG00000069399; -.
DR PharmGKB; PA25310; -.
DR VEuPathDB; HostDB:ENSG00000069399; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000161392; -.
DR HOGENOM; CLU_720685_0_0_1; -.
DR InParanoid; P20749; -.
DR OMA; MMCSMEH; -.
DR OrthoDB; 621606at2759; -.
DR PhylomeDB; P20749; -.
DR TreeFam; TF320166; -.
DR PathwayCommons; P20749; -.
DR SignaLink; P20749; -.
DR SIGNOR; P20749; -.
DR BioGRID-ORCS; 602; 14 hits in 1160 CRISPR screens.
DR ChiTaRS; BCL3; human.
DR EvolutionaryTrace; P20749; -.
DR GeneWiki; BCL3; -.
DR GenomeRNAi; 602; -.
DR Pharos; P20749; Tchem.
DR PRO; PR:P20749; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P20749; Protein.
DR Bgee; ENSG00000069399; Expressed in left uterine tube and 177 other cell types or tissues.
DR ExpressionAtlas; P20749; baseline and differential.
DR Genevisible; P20749; HS.
DR GO; GO:0032996; C:Bcl3-Bcl10 complex; IDA:UniProtKB.
DR GO; GO:0033257; C:Bcl3/NF-kappaB2 complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030496; C:midbody; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0019730; P:antimicrobial humoral response; IEA:Ensembl.
DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0042832; P:defense response to protozoan; IEA:Ensembl.
DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0002268; P:follicular dendritic cell differentiation; IEA:Ensembl.
DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl.
DR GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI.
DR GO; GO:0002315; P:marginal zone B cell differentiation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of type II interferon production; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0051101; P:regulation of DNA binding; IEP:UniProtKB.
DR GO; GO:1901222; P:regulation of non-canonical NF-kappaB signal transduction; IEP:UniProtKB.
DR GO; GO:0010225; P:response to UV-C; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl.
DR GO; GO:0045064; P:T-helper 2 cell differentiation; IEA:Ensembl.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR IDEAL; IID00445; -.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR PANTHER; PTHR24118:SF51; B-CELL LYMPHOMA 3 PROTEIN; 1.
DR PANTHER; PTHR24118; POTE ANKYRIN DOMAIN; 1.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 2.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; ANK repeat; Chromosomal rearrangement; Cytoplasm;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..454
FT /note="B-cell lymphoma 3 protein"
FT /id="PRO_0000066976"
FT REPEAT 134..163
FT /note="ANK 1"
FT REPEAT 171..200
FT /note="ANK 2"
FT REPEAT 204..235
FT /note="ANK 3"
FT REPEAT 241..270
FT /note="ANK 4"
FT REPEAT 275..304
FT /note="ANK 5"
FT REPEAT 308..337
FT /note="ANK 6"
FT REPEAT 338..367
FT /note="ANK 7"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..403
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..431
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..454
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 402
FT /note="Phosphoserine; by GSK3"
FT /evidence="ECO:0000269|PubMed:15469820"
FT MOD_RES 406
FT /note="Phosphoserine; by GSK3"
FT /evidence="ECO:0000269|PubMed:15469820"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 148..160
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 175..181
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 185..193
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 208..214
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 218..227
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 245..252
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 255..263
FT /evidence="ECO:0007829|PDB:1K1A"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 279..285
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 289..297
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 312..319
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:1K1A"
FT TURN 345..348
FT /evidence="ECO:0007829|PDB:1K1A"
FT HELIX 352..358
FT /evidence="ECO:0007829|PDB:1K1A"
SQ SEQUENCE 454 AA; 47584 MW; 385F5320DB72C0E0 CRC64;
MPRCPAGAMD EGPVDLRTRP KAAGLPGAAL PLRKRPLRAP SPEPAAPRGA AGLVVPLDPL
RGGCDLPAVP GPPHGLARPE ALYYPGALLP LYPTRAMGSP FPLVNLPTPL YPMMCPMEHP
LSADIAMATR ADEDGDTPLH IAVVQGNLPA VHRLVNLFQQ GGRELDIYNN LRQTPLHLAV
ITTLPSVVRL LVTAGASPMA LDRHGQTAAH LACEHRSPTC LRALLDSAAP GTLDLEARNY
DGLTALHVAV NTECQETVQL LLERGADIDA VDIKSGRSPL IHAVENNSLS MVQLLLQHGA
NVNAQMYSGS SALHSASGRG LLPLVRTLVR SGADSSLKNC HNDTPLMVAR SRRVIDILRG
KATRPASTSQ PDPSPDRSAN TSPESSSRLS SNGLLSASPS SSPSQSPPRD PPGFPMAPPN
FFLPSPSPPA FLPFAGVLRG PGRPVPPSPA PGGS
//
