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   04-NOV-2026, entry version 225.
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.
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};
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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_005178.5.
DR   PDB; 1K1A; X-ray; 1.86 A; A=127-367.
DR   PDB; 1K1B; X-ray; 1.90 A; A=127-367.
DR   AlphaFoldDB; P20749; -.
DR   SMR; P20749; -.
DR   BioGRID; 107074; 50.
DR   CORUM; P20749; -.
DR   FunCoup; P20749; 312.
DR   IntAct; P20749; 12.
DR   NDEx; IQUERY-CP-BCL3; 3 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000164227; -.
DR   ChEMBL; CHEMBL4523197; -.
DR   GuidetoPHARMACOLOGY; 3232; -.
DR   iPTMnet; P20749; -.
DR   PhosphoSitePlus; P20749; -.
DR   BioMuta; BCL3; -.
DR   DMDM; 294862410; -.
DR   jPOST; P20749; -.
DR   MassIVE; P20749; -.
DR   PaxDb; 9606-ENSP00000164227; -.
DR   PeptideAtlas; P20749; -.
DR   ProteomicsDB; 53783; -.
DR   Pumba; P20749; -.
DR   Antibodypedia; 3672; 452 antibodies from 44 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   ClinPGx; PA25310; -.
DR   CTD; 602; -.
DR   DisGeNET; 602; -.
DR   GeneCards; BCL3; -.
DR   HGNC; HGNC:998; BCL3.
DR   HPA; ENSG00000069399; Tissue enhanced (liver).
DR   MalaCards; BCL3; -.
DR   MIM; 109560; gene.
DR   OpenTargets; ENSG00000069399; -.
DR   VEuPathDB; HostDB:ENSG00000069399; -.
DR   eggNOG; KOG0504; Eukaryota.
DR   GeneTree; ENSGT00940000161392; -.
DR   HOGENOM; CLU_720685_0_0_1; -.
DR   InParanoid; P20749; -.
DR   OMA; ACPLWPF; -.
DR   OrthoDB; 10254947at2759; -.
DR   PAN-GO; P20749; 7 GO annotations based on evolutionary models.
DR   PhylomeDB; P20749; -.
DR   PathwayCommons; P20749; -.
DR   SignaLink; P20749; -.
DR   SIGNOR; P20749; -.
DR   Agora; ENSG00000069399; -.
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   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: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: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:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR   GO; GO:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProtKB.
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:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI.
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:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR   GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
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: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   FunFam; 1.25.40.20:FF:000187; B-cell lymphoma 3 protein; 1.
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   InterPro; IPR051070; NF-kappa-B_inhibitor.
DR   PANTHER; PTHR46680; NF-KAPPA-B INHIBITOR ALPHA; 1.
DR   PANTHER; PTHR46680:SF2; NF-KAPPA-B INHIBITOR ZETA; 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; Proteomics identification; Proto-oncogene;
KW   Reference proteome; Repeat; Transcription; Transcription regulation;
KW   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        21..31
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        365..381
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        382..404
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        405..418
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        432..442
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        443..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
//