P41182 (BCL6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
B-cell lymphoma 6 protein
Short name=BCL-6

Alternative name(s):
B-cell lymphoma 5 protein
Short name=BCL-5
Protein LAZ-3
Zinc finger and BTB domain-containing protein 27
Zinc finger protein 51

Gene names

Name:	BCL6
Synonyms:	BCL5, LAZ3, ZBTB27, ZNF51

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	706 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis. Ref.7 Ref.12
Subunit structure	Homodimer. Interacts (via BTB domain) with BCOR; the interaction is direct. Interacts (via BTB domain) with NCOR2; the interaction is direct. Interacts with ZBTB7 and BCL6B By similarity. Interacts with the catalytic domain of HDAC9. Ref.8 Ref.12
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in germinal center T and B cells and in primary immature dendritic cells. Ref.7 Ref.9
Induction	Down-regulated during maturation of dendritic cells by selective stimuli such as bacterial lipopolysaccharides (LPS), CD40LG and zymosan. Ref.9
Domain	The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2.
Post-translational modification	Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-333 and Ser-343. Phosphorylation induces its degradation by ubiquitin/proteasome pathway. Ref.7 Polyubiquitinated. Polyubiquitination leads to degradation by the proteasome.
Involvement in disease	Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Sequence similarities	Contains 1 BTB (POZ) domain. Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of B cell apoptosis Non-traceable author statement. Source: UniProtKB negative regulation of S phase of mitotic cell cycle Non-traceable author statement. Source: UniProtKB negative regulation of cell growth Inferred from direct assay. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB positive regulation of apoptotic process Inferred from direct assay. Source: UniProtKB protein import into nucleus, translocation Inferred from genetic interaction. Source: UniProtKB regulation of germinal center formation Non-traceable author statement. Source: UniProtKB response to DNA damage stimulus Inferred from direct assay. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HDAC4	P56524	3	EBI-765407,EBI-308629
HDAC9	Q9UKV0	2	EBI-765407,EBI-765444
ZMYND8	Q9ULU4	3	EBI-765407,EBI-765834

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 706

706

B-cell lymphoma 6 protein

PRO_0000047098

Regions

Domain

32 – 99

68

BTB

Zinc finger

518 – 541

24

C2H2-type 1

Zinc finger

546 – 568

23

C2H2-type 2

Zinc finger

574 – 596

23

C2H2-type 3

Zinc finger

602 – 624

23

C2H2-type 4

Zinc finger

630 – 652

23

C2H2-type 5

Zinc finger

658 – 681

24

C2H2-type 6

Amino acid modifications

Modified residue

333

1

Phosphoserine; by MAPK1 Ref.7

Modified residue

343

1

Phosphoserine; by MAPK1 Ref.7

Natural variations

Natural variant

252

1

N → S.
Corresponds to variant rs34463990 [ dbSNP | Ensembl ].

VAR_052709

Natural variant

493

1

A → T.
Corresponds to variant rs2229362 [ dbSNP | Ensembl ].

VAR_019970

Natural variant

676

1

H → Y.
Corresponds to variant rs1056936 [ dbSNP | Ensembl ].

VAR_014825

Experimental info

Mutagenesis

333

1

S → A: Decrease in phosphorylation by MAPK1. Ref.7

Mutagenesis

343

1

S → A: Decrease in phosphorylation by MAPK1. Ref.7

Sequence conflict

347

1

S → A in AAC50054. Ref.2

Sequence conflict

393

1

E → G in AAC50054. Ref.2

Sequence conflict

498

1

P → A in AAC50054. Ref.2

Secondary structure

1

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706

Helix Strand Turn

Details...

Helix

14 – 27

14

Beta strand

34 – 38

5

Beta strand

41 – 45

5

Helix

47 – 53

7

Helix

55 – 61

7

Turn

64 – 68

5

Beta strand

70 – 73

4

Helix

80 – 92

13

Beta strand

93 – 95

3

Turn

99 – 101

3

Helix

102 – 111

10

Helix

115 – 126

12

Beta strand

521 – 523

3

Beta strand

527 – 529

3

Helix

530 – 540

11

Beta strand

601 – 603

3

Turn

605 – 607

3

Beta strand

610 – 613

4

Helix

614 – 620

7

Helix

622 – 625

4

Beta strand

633 – 635

3

Beta strand

639 – 641

3

Helix

642 – 648

7

Turn

649 – 652

4

Sequences

	Sequence		Length	Mass (Da)
	P41182 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: E38D83C213DAE2D0	FASTA	706	78,846
	10 20 30 40 50 60 MASPADSCIQ FTRHASDVLL NLNRLRSRDI LTDVVIVVSR EQFRAHKTVL MACSGLFYSI 70 80 90 100 110 120 FTDQLKCNLS VINLDPEINP EGFCILLDFM YTSRLNLREG NIMAVMATAM YLQMEHVVDT 130 140 150 160 170 180 CRKFIKASEA EMVSAIKPPR EEFLNSRMLM PQDIMAYRGR EVVENNLPLR SAPGCESRAF 190 200 210 220 230 240 APSLYSGLST PPASYSMYSH LPVSSLLFSD EEFRDVRMPV ANPFPKERAL PCDSARPVPG 250 260 270 280 290 300 EYSRPTLEVS PNVCHSNIYS PKETIPEEAR SDMHYSVAEG LKPAAPSARN APYFPCDKAS 310 320 330 340 350 360 KEEERPSSED EIALHFEPPN APLNRKGLVS PQSPQKSDCQ PNSPTESCSS KNACILQASG 370 380 390 400 410 420 SPPAKSPTDP KACNWKKYKF IVLNSLNQNA KPEGPEQAEL GRLSPRAYTA PPACQPPMEP 430 440 450 460 470 480 ENLDLQSPTK LSASGEDSTI PQASRLNNIV NRSMTGSPRS SSESHSPLYM HPPKCTSCGS 490 500 510 520 530 540 QSPQHAEMCL HTAGPTFPEE MGETQSEYSD SSCENGAFFC NECDCRFSEE ASLKRHTLQT 550 560 570 580 590 600 HSDKPYKCDR CQASFRYKGN LASHKTVHTG EKPYRCNICG AQFNRPANLK THTRIHSGEK 610 620 630 640 650 660 PYKCETCGAR FVQVAHLRAH VLIHTGEKPY PCEICGTRFR HLQTLKSHLR IHTGEKPYHC 670 680 690 700 EKCNLHFRHK SQLRLHLRQK HGAITNTKVQ YRVSATDLPP ELPKAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas." Kerckaert J.-P., Deweindt C., Tilly H., Quief S., Lecocq G., Bastard C. Nat. Genet. 5:66-70(1993) [PubMed: 8220427] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma." Ye B.H., Lista F., Lo Coco F., Knowles D.M., Offit K., Chaganti R.S.K., Dalla-Favera R. Science 262:747-750(1993) [PubMed: 8235596] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Kruppel-like zinc-finger protein." Miki T., Kawamata N., Hirosawa S., Aoki N. Blood 83:26-32(1994) [PubMed: 8274740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas." Baron B.W., Nucifora G., McCabe N., Espinosa R. III, le Beau M.M., McKeithan T.W. Proc. Natl. Acad. Sci. U.S.A. 90:5262-5266(1993) [PubMed: 8506375] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor." Niu H., Ye B.H., Dalla-Favera R. Genes Dev. 12:1953-1961(1998) [PubMed: 9649500] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-333 AND SER-343, MUTAGENESIS OF SER-333 AND SER-343, UBIQUITINATION.
[8]	"The histone deacetylase 9 gene encodes multiple protein isoforms." Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A. J. Biol. Chem. 278:16059-16072(2003) [PubMed: 12590135] [Abstract] Cited for: INTERACTION WITH HDAC9.
[9]	"Plastic downregulation of the transcriptional repressor BCL6 during maturation of human dendritic cells." Pantano S., Jarrossay D., Saccani S., Bosisio D., Natoli G. Exp. Cell Res. 312:1312-1322(2006) [PubMed: 16455075] [Abstract] Cited for: INDUCTION, TISSUE SPECIFICITY.
[10]	"Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain." Ahmad K.F., Melnick A., Lax S., Bouchard D., Liu J., Kiang C.L., Mayer S., Takahashi S., Licht J.D., Prive G.G. Mol. Cell 12:1551-1564(2003) [PubMed: 14690607] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 5-129 IN COMPLEX WITH NCOR2.
[11]	"Solution structure of the C2H2 type zinc finger (region 598-654) of human B-cell lymphoma 6 protein." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 598-657.
[12]	"Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer." Ghetu A.F., Corcoran C.M., Cerchietti L., Bardwell V.J., Melnick A., Prive G.G. Mol. Cell 29:384-391(2008) [PubMed: 18280243] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 5-129 IN COMPLEX WITH BCOR, FUNCTION, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z21943 mRNA. Translation: CAA79937.1.
U00115 mRNA. Translation: AAC50054.1.
S67779 mRNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78140.1.
CH471052 Genomic DNA. Translation: EAW78141.1.
BC150184 mRNA. Translation: AAI50185.1.

IPI

IPI00012820.

PIR

A48752.
I52586.

RefSeq

NP_001124317.1. NM_001130845.1.
NP_001128210.1. NM_001134738.1.
NP_001697.2. NM_001706.4.

UniGene

Hs.478588.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R28	X-ray	2.20	A/B	5-129	[»]
1R29	X-ray	1.30	A	5-129	[»]
1R2B	X-ray	2.20	A/B	5-129	[»]
2EN2	NMR	-	A	598-626	[»]
2EOS	NMR	-	A	626-654	[»]
2LCE	NMR	-	A	540-602	[»]
2YRM	NMR	-	A	515-544	[»]
3BIM	X-ray	2.60	A/B/C/D/E/F/G/H	5-129	[»]
3E4U	X-ray	2.10	A/B/C/D/E/F	5-129	[»]
3LBZ	X-ray	2.30	A/B	5-129	[»]

ProteinModelPortal

P41182.

SMR

P41182. Positions 5-129, 471-680.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2651N.

IntAct

P41182. 66 interactions.

MINT

MINT-158757.

STRING

P41182.

PTM databases

PhosphoSite

P41182.

Polymorphism databases

DMDM

728952.

Proteomic databases

PRIDE

P41182.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000232014; ENSP00000232014; ENSG00000113916.
ENST00000406870; ENSP00000384371; ENSG00000113916.

GeneID

604.

KEGG

hsa:604.

UCSC

uc003frp.2. human.

Organism-specific databases

CTD

604.

GeneCards

GC03M187439.

H-InvDB

HIX0024343.

HGNC

HGNC:1001. BCL6.

HPA

CAB000307.
HPA004899.

MIM

109565. gene.

neXtProt

NX_P41182.

Orphanet

544. Diffuse large B-cell lymphoma.
545. Follicular lymphoma.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11184.

GeneTree

ENSGT00600000084004.

HOGENOM

HBG445860.

HOVERGEN

HBG004831.

InParanoid

P41182.

OMA

QASFRYK.

OrthoDB

EOG4NVZJS.

PhylomeDB

P41182.

Enzyme and pathway databases

Pathway_Interaction_DB

foxopathway. FoxO family signaling.
il4_2pathway. IL4-mediated signaling events.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.

Gene expression databases

ArrayExpress

P41182.

Bgee

P41182.

CleanEx

HS_BCL6.

Genevestigator

P41182.

GermOnline

ENSG00000113916. Homo sapiens.

Family and domain databases

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.
G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 5 hits.

KO

K15618.

Pfam

PF00651. BTB. 1 hit.
PF00096. zf-C2H2. 4 hits.
[Graphical view]

SMART

SM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 6 hits.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.

PROSITE

PS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 6 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2453.

SOURCE

Search...

Entry information

Entry name

BCL6_HUMAN

Accession

Primary (citable) accession number: P41182
Secondary accession number(s): A7E241, D3DNV5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	January 25, 2012
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.