BCL6 BCL6 transcription repressor [Homo sapiens (human)] - Gene

Summary

Official Symbol: BCL6provided by HGNC
Official Full Name: BCL6 transcription repressorprovided by HGNC
Primary source: HGNC:HGNC:1001
See related: Ensembl:ENSG00000113916 MIM:109565
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BCL5; LAZ3; BCL6A; ZNF51; ZBTB27
Summary: The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
Expression: Ubiquitous expression in fat (RPKM 29.2), bone marrow (RPKM 20.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 3q27.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	3	NC_000003.12 (187721377..187745725, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (187439165..187463513, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL
Title: Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90.
ML364 decreases the BCL6 protein stability in K562/G01 by inhibiting the USP2-mediated deubiquitination, and down-regulate the BCL6 protein experssion
Title: [Effects of Ubiquitination on the Expression of BCL6 Protein，Cell Proliferation and Apoptosis in K562/G01 Cells].
Study identified RANKL and BCL6 mRNA as targets of AUF1 p42. Detailed analysis of 3'UTRs revealed for both that full instability required two elements, which are conserved in evolution. In RANKL mRNA both elements are AU-rich and separated by 30 bases, while in BCL6 mRNA one is AU-rich and 60 bases from a non-AU-rich element that potentially forms a stem-loop structure.
Title: Short-lived AUF1 p42-binding mRNAs of RANKL and BCL6 have two distinct instability elements each.
BCL6 attenuates proliferation and oxidative stress of vascular smooth muscle cells in hypertension.
Title: BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension.
Studied role of B cell CLL/lymphoma 6 (BCL6) in malignancy and found BCL6 is expressed at a high level in glioma when compared with non-tumor brain tissues. The downregulation of BCL6 was shown to inhibit proliferation, migration, and invasion, promote apoptosis, and induce cell cycle arrest via the AKT and MAPK pathway.
Title: Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway.
KRAS, SIRT1 and BCL6 are coordinately over-expressed in eutopic endometrium of women with endometriosis
Title: KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance.
BCL6 translocation was detected in 15 (12%) cases. Translocation involving MYC and BCL2 was identified in 3 cases (3.8%) and 1 case (1.3%) respectively. One double hit lymphoma was discovered with both MYC/BCL2 translocation (1.3%).
Title: MYC, BCL2, and BCL6 rearrangements in primary central nervous system lymphoma of large B cell type.
Fluorescence in situ hybridization studies (histologic sections) confirmed translocations of MYC (8q24), BCL2 (18q21) and BCL6 (3q27) in all patients.
Title: "Triple hit" lymphomas: A retrospective cytology case series of an uncommon high grade B-cell malignancy with C-MYC, BCL-2 and BCL-6 rearrangements.
our exploratory study suggests that EOMES, BCL6 and GZMB gene expression are aberrant within the PB T cell transcriptome of HT patients. The association of this transcription signature with the heterogeneity of HT and disease control is suggested.
Title: Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto's thyroiditis - an observational study.
Cryptic t(3;8)(q27;q24) and/or MYC-BCL6 linkage associated with MYC expression by immunohistochemistry is frequent in multiple-hit B-cell lymphomas
Title: Cryptic t(3;8)(q27;q24) and/or MYC-BCL6 linkage associated with MYC expression by immunohistochemistry is frequent in multiple-hit B-cell lymphomas.

Submit: New GeneRIF Correction See all GeneRIFs (258)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Generalization of variants identified by genome-wide association studies for electrocardiographic traits in African Americans. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of B cell non-Hodgkin lymphoma identifies 3q27 as a susceptibility locus in the Chinese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of B-cell CLL/lymphoma 6 (BCL6) in human B cells	PubMed
Tat	tat	HIV-1 Tat upregulates the expression of T-bet, Eomesdermin, Blimp-1, Bcl-6, and Bcl-2 in stimulated but not in unstimulated CD8+T lymphocytes	PubMed
	tat	HIV-1 Tat upregulates the expression of BCL-6 in Kaposi's sarcoma cells and human primary T cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
B Cell Receptor Signaling Pathway, organism-specific biosystemThe functional B-cell receptor is a multi-protein complex consisting of an antigen binding subunit and a signaling subunit. The antigen binding subunit is the membrane bound immunoglobulin and the si...
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
DNA Damage Response (only ATM dependent), organism-specific biosystem (from WikiPathways)
DNA Damage Response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...
Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
Direct p53 effectors, organism-specific biosystem
Direct p53 effectors
FoxO family signaling, organism-specific biosystem (from Pathway Interaction Database)
FoxO family signaling, organism-specific biosystem
FoxO family signaling
FoxO signaling pathway, organism-specific biosystem (from KEGG)
FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL4-mediated signaling events, organism-specific biosystem
IL4-mediated signaling events
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Interleukin-4 and 13 signaling, organism-specific biosystem (from REACTOME)
Interleukin-4 and 13 signaling, organism-specific biosystemInterleukin-4 (IL4) is a principal regulatory cytokine during the immune response, crucially important in allergy and asthma (Nelms et al. 1999). When resting T cells are antigen-activated and expand...
MECP2 and Associated Rett Syndrome, organism-specific biosystem (from WikiPathways)
MECP2 and Associated Rett Syndrome, organism-specific biosystemMecp2 is in many mammals an important regulator of neuronal function and development. It affects all cell types, especially neurons but also astrocytes, oligodendrocytes, and glial cells. Mecp2 plays...
Signaling by Interleukins, organism-specific biosystem (from REACTOME)
Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
Signaling events mediated by HDAC Class II, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by HDAC Class II, organism-specific biosystem
Signaling events mediated by HDAC Class II
TP53 Regulates Transcription of Cell Death Genes, organism-specific biosystem (from REACTOME)
TP53 Regulates Transcription of Cell Death Genes, organism-specific biosystemThe tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptot...
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain, organism-specific biosystem (from REACTOME)
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain, organism-specific biosystemThe exact mechanisms of action of several other pro-apoptotic TP53 (p53) targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP, remain uncertain (Attardi et al. 2000, Guo et al. 2001...
Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...
Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
Transcriptional misregulation in cancer, organism-specific biosystem
Transcriptional misregulation in cancer
Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
Transcriptional misregulation in cancer, conserved biosystem
Transcriptional misregulation in cancer

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-77640 (e-PCR)
- UniSTS:58625

SHGC-64334 (e-PCR)
- UniSTS:34563

RH70520 (e-PCR)
- UniSTS:64302

STS-W46183 (e-PCR)
- UniSTS:74552

SHGC-77610 (e-PCR)
- UniSTS:82745

RH47862 (e-PCR)
- UniSTS:18348

BCL6 (e-PCR)
- UniSTS:505525

PMC309637P2 (e-PCR)
- UniSTS:272596

RH69801 (e-PCR)
- UniSTS:61681

PMC137537P1 (e-PCR)
- UniSTS:270834

SHGC-34056 (e-PCR)
- UniSTS:19451

Homology

Homologs of the BCL6 gene: The BCL6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 265 organisms have orthologs with human gene BCL6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription repressor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA polymerase II regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chromatin DNA binding	IEA Inferred from Electronic Annotation more info
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
intronic transcription regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
B cell differentiation	IEA Inferred from Electronic Annotation more info
Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
cell morphogenesis	IEA Inferred from Electronic Annotation more info
cellular response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
erythrocyte development	IEA Inferred from Electronic Annotation more info
germinal center formation	IEA Inferred from Electronic Annotation more info
inflammatory response	IEA Inferred from Electronic Annotation more info
negative regulation of B cell apoptotic process	NAS Non-traceable Author Statement more info	PubMed
negative regulation of Notch signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
negative regulation of T-helper 2 cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of cell-matrix adhesion	IEA Inferred from Electronic Annotation more info
negative regulation of cellular senescence	IEA Inferred from Electronic Annotation more info
negative regulation of isotype switching to IgE isotypes	IEA Inferred from Electronic Annotation more info
negative regulation of mast cell cytokine production	IEA Inferred from Electronic Annotation more info
negative regulation of mitotic cell cycle DNA replication	NAS Non-traceable Author Statement more info	PubMed
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription, DNA-templated	NAS Non-traceable Author Statement more info	PubMed
positive regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cellular component movement	IEA Inferred from Electronic Annotation more info
positive regulation of histone deacetylation	IEA Inferred from Electronic Annotation more info
positive regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of regulatory T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
protein localization	IEA Inferred from Electronic Annotation more info
regulation of GTPase activity	IEA Inferred from Electronic Annotation more info
regulation of apoptotic process	TAS Traceable Author Statement more info
regulation of cell proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of germinal center formation	NAS Non-traceable Author Statement more info	PubMed
regulation of immune response	NAS Non-traceable Author Statement more info	PubMed
regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of memory T cell differentiation	IEA Inferred from Electronic Annotation more info
spermatogenesis	IEA Inferred from Electronic Annotation more info
type 2 immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with replication fork	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: B-cell lymphoma 6 protein

Names: B cell CLL/lymphoma 6; B-cell lymphoma 5 protein; B-cell lymphoma 6 protein transcript; BCL-5; BCL-6; cys-his2 zinc finger transcription factor; lymphoma-associated zinc finger gene on chromosome 3; protein LAZ-3; zinc finger and BTB domain-containing protein 27; zinc finger protein 51; zinc finger transcription factor BCL6S

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007149.1 RefSeqGene

Range

4811..29159

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001130845.1 → NP_001124317.1 B-cell lymphoma 6 protein isoform 1

See identical proteins and their annotated locations for NP_001124317.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has a downstream and alternate 5' UTR exon, as compared to variant 1.

Source sequence(s)

AW470156, BC146796, BC150184, CN401512

Consensus CDS

CCDS3289.1

UniProtKB/Swiss-Prot

P41182

Related

ENSP00000232014.4, ENST00000232014.8

Conserved Domains (4) summary

smart00225
Location:33 → 126

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00017
Location:576 → 596

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:22 → 126

BTB; BTB/POZ domain

pfam13465
Location:588 → 613

zf-H2C2_2; Zinc-finger double domain
NM_001134738.1 → NP_001128210.1 B-cell lymphoma 6 protein isoform 2

See identical proteins and their annotated locations for NP_001128210.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks a coding exon, as compared to variant 1. The reading frame is not affected and the resulting isoform (2) lacks an internal segment, as compared to isoform 2.

Source sequence(s)

AW337942, BC146796, BC150184, EU883531, Z21943

Consensus CDS

CCDS46975.1

UniProtKB/Swiss-Prot

P41182

UniProtKB/TrEMBL

B5B0A5

Related

ENSP00000413122.2, ENST00000450123.6

Conserved Domains (5) summary

smart00225
Location:33 → 126

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00017
Location:520 → 540

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:518 → 540

zf-C2H2; Zinc finger, C2H2 type

pfam00651
Location:22 → 126

BTB; BTB/POZ domain

pfam13465
Location:532 → 557

zf-H2C2_2; Zinc-finger double domain
NM_001706.5 → NP_001697.2 B-cell lymphoma 6 protein isoform 1

See identical proteins and their annotated locations for NP_001697.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) and variant 2 encode the same isoform (1).

Source sequence(s)

BC146796, BC150184, DB079847

Consensus CDS

CCDS3289.1

UniProtKB/Swiss-Prot

P41182

Related

ENSP00000384371.2, ENST00000406870.7

Conserved Domains (4) summary

smart00225
Location:33 → 126

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00017
Location:576 → 596

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:22 → 126

BTB; BTB/POZ domain

pfam13465
Location:588 → 613

zf-H2C2_2; Zinc-finger double domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p12 Primary Assembly

Range

187721377..187745725 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011513062.3 → XP_011511364.1 B-cell lymphoma 6 protein isoform X2

See identical proteins and their annotated locations for XP_011511364.1

UniProtKB/Swiss-Prot

P41182

Related

ENSP00000479784.1, ENST00000621333.4

Conserved Domains (5) summary

smart00225
Location:33 → 126

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00017
Location:520 → 540

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:518 → 540

zf-C2H2; Zinc finger, C2H2 type

pfam00651
Location:22 → 126

BTB; BTB/POZ domain

pfam13465
Location:532 → 557

zf-H2C2_2; Zinc-finger double domain
XM_005247694.4 → XP_005247751.1 B-cell lymphoma 6 protein isoform X1

See identical proteins and their annotated locations for XP_005247751.1

UniProtKB/Swiss-Prot

P41182

Conserved Domains (4) summary

smart00225
Location:33 → 126

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00017
Location:576 → 596

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:22 → 126

BTB; BTB/POZ domain

pfam13465
Location:588 → 613

zf-H2C2_2; Zinc-finger double domain

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_138931.1: Suppressed sequence

Description

NM_138931.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.