BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2)
2010-01-01 Malene Krag Kjeldsen  , Karen Dybkaer  , Jinghua Liu  , Finn Skou Pedersen   AffiliationDNA/RNA
Description
NCBI Reference Sequence: NC_000006.11;
370316 bp DNA;
BACH2 consists of 9 exons and 8 intervening introns.
RNA:
NCBI Reference Sequence: NM_021813.2;
9215 bp mRNA.
Transcription
Pseudogene
Proteins
Description
BACH2 contains 841 amino acid residues with a molecular weight of 92536 Da.
BACH2 belongs to the bZIP family and CNC subfamily.
BACH2 contains a BTB domain for protein interaction in the N-terminal region starting at amino acid residue 37 to 103. In the C-terminus from amino acid residue 651 to amino acid residue 666 a basic DNA binding domain, followed by a hydrophobic leucine zipper domain ranging from amino acid residue 674 to 695 responsible for dimerisation.
The four alternative spliced variants generate four different proteins:
1) BACH2-003, transcript ID: ENST00000257749 and protein ID: ENSP00000257749. This transcript contains all 9 exons and have the full length transcript at 9215 bps and a full length protein with 841 aa.
2) BACH2-005, transcript ID: ENST00000343122 and protein ID: ENSP00000345642. This transcript contains 7 exons (1, 4, 5, 6, 7, 8, 9) resulting in a transcript with 3981 bps and a protein with 841 aa.
3) BACH2-002, transcript ID: ENST00000406998 and protein ID: ENSP00000384145. This transcript contains only 4 alternative exons (1, 4, 5, 6) producing a transcript at 780 bps and a protein with 81 aa. This alternative protein only contains the BTB domain.
4) BACH2-007, transcript ID : ENST00000453877 and protein ID: ENSP00000397668. This transcript contains only 5 alternative exons (1, 2, 4, 5, 6), producing a transcript at 868 bps and 81 aa. This alterniative protein only contains the BTB domain.
Liu et al. have, in mice, identified an alternative promoter and new isoforms of BACH2 by using murine insertional mutagenesis (Liu et al., 2009).
Related proteins:
BACH1 and BACH2 are highly homologous proteins with significant similarity to each other in the bZIP and BTB domains. But the expression pattern and function of the two proteins are different. BACH1 is more ubiquitously expressed whereas BACH2 expression is restricted to mononuclear and neuronal cells. (Shim et al., 2006; Hoshino and Igarashi, 2002; Muto et al., 1998; Oyake et al., 1996).
Expression
Localisation
Function
BACH2 in B-cell differentation:
BACH2 is critical for antibody responses including class switch recombination (CSR) and somatic hypermutation (SH) of immunoglobulin genes (Muto et al., 2004). BACH2 and Bcl-6 cooporates to repress Prdm1, and thereby regulating B-cell differentiation through the germinal center (Ochiai et al., 2008).
Neuronal differentiation:
BACH2 seems to be involed in neuronal differentiation, by upregulating both cytoplasmic and nuclear p21 protein levels. P21 is a cdk inhibitor known to arrest the cell cycle. In N1E-115 cells regulation of differentiation involves a down regulation of cellular proliferation (Shim et al., 2006).
Immune response:
BACH2 is involved in the antiviral response triggered by dsRNA or dsDNA molecular patterns (Hong et al., 2008).
Homology
NP_068585.1 BACH2 Homo sapiens
XP_539044.2 BACH2 Canis lupus familiaris
XP_618496.2 BACH2 Bos taurus
XP_232858.3 RGD1562865 Rattus norvegicus
XP_419833.2 BACH2 Gallus gallus
XP_682933.2 bach2 Danio rerio
Mutations
Note
Bach2 is considered a B-cell specific tumor suppressor since loss of heterozygosity (LOH) is frequently observed for non-hodgkin lymphomas (Sasaki et al., 2000).
High throughput screens using retroviral and transposon insertion into mouse models have identified BACH2 as a common insertion site (CIS) (http://rtcgd.abcc.ncifcrf.gov/). BACH2 expression is in these models disrupted or activated in the resulting B cell tumours.
Homozygous null mice display impaired B cell differentiation and reduced B cell numbers.
Implicated in
The translocation between the Bcl-2 and the immunoglobulin heavy-chain (IgH) gene, t(14;18)(q21;q34), is a common genetic alteration in follicular and DLBCL lymphomas, bringing the antiapoptotic Bcl-2 gene under regulation of the active IgH promoter in B-cells. This translocation should result in an upregulation of Bcl-2 due to the activity of the IgH promoter in B-cells. Green et al. demonstrated that patients with t(14;18) and a high expression of BACH2 had significantly lower Bcl-2 expression from the t(14;18) translocation (Green et al., 2009).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18978792 | 2008 | Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. | Cooper JD et al |
| 18840781 | 2009 | Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. | Grant SF et al |
| 18929412 | 2009 | High levels of BACH2 associated with lower levels of BCL2 transcript abundance in t(14;18)(q21;q34) translocation positive non-Hodgkin's lymphoma. | Green M et al |
| 17991429 | 2008 | The role of Bach2 in nucleic acid-triggered antiviral innate immune responses. | Hong SW et al |
| 12204112 | 2002 | Expression of the oxidative stress-regulated transcription factor bach2 in differentiating neuronal cells. | Hoshino H et al |
| 10809773 | 2000 | Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element. | Hoshino H et al |
| 17569706 | 2007 | Architecture and dynamics of the transcription factor network that regulates B-to-plasma cell differentiation. | Igarashi K et al |
| 12829606 | 2003 | B-cell-specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs. | Kamio T et al |
| 10669750 | 2000 | A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain. | Kobayashi A et al |
| 18769450 | 2008 | Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells. | Lesniewski ML et al |
| 19159451 | 2009 | Identification of novel Bach2 transcripts and protein isoforms through tagging analysis of retroviral integrations in B-cell lymphomas. | Liu J et al |
| 16832351 | 2007 | Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression. | Motamed-Khorasani A et al |
| 9755173 | 1998 | Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3' enhancer. | Muto A et al |
| 15152264 | 2004 | The transcriptional programme of antibody class switching involves the repressor Bach2. | Muto A et al |
| 17046816 | 2006 | Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells. | Ochiai K et al |
| 18256039 | 2008 | Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6. | Ochiai K et al |
| 8887638 | 1996 | Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. | Oyake T et al |
| 16258099 | 2005 | Prognostic significance of BACH2 expression in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. | Sakane-Ishikawa E et al |
| 10949928 | 2000 | Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15. | Sasaki S et al |
| 16631738 | 2006 | Bach2 is involved in neuronal differentiation of N1E-115 neuroblastoma cells. | Shim KS et al |
| 14982850 | 2004 | Integration of Epstein-Barr virus into chromosome 6q15 of Burkitt lymphoma cell line (Raji) induces loss of BACH2 expression. | Takakuwa T et al |
| 11746976 | 2001 | Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL oncogene. | Vieira SA et al |
| 17018862 | 2007 | Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1. | Yoshida C et al |
Other Information
Locus ID:
NCBI: 60468
MIM: 605394
HGNC: 14078
Ensembl: ENSG00000112182
Variants:
dbSNP: 60468
ClinVar: 60468
TCGA: ENSG00000112182
COSMIC: BACH2
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38459508 | 2024 | The role of Bach2 in regulating CD8 + T cell development and function. | 0 |
| 38459508 | 2024 | The role of Bach2 in regulating CD8 + T cell development and function. | 0 |
| 36573315 | 2023 | Exploring novel functions of BACH2 in the acquisition of antigen-specific antibodies. | 4 |
| 36781170 | 2023 | Bach2 in CD4(+) T cells from SLE patients modulates B-cell differentiation and IgG production. | 0 |
| 36573315 | 2023 | Exploring novel functions of BACH2 in the acquisition of antigen-specific antibodies. | 4 |
| 36781170 | 2023 | Bach2 in CD4(+) T cells from SLE patients modulates B-cell differentiation and IgG production. | 0 |
| 35264460 | 2022 | CRISPR/Cas9-Mediated Insertion of HIV Long Terminal Repeat within BACH2 Promotes Expansion of T Regulatory-like Cells. | 5 |
| 35544467 | 2022 | Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients. | 2 |
| 36178457 | 2022 | BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis. | 5 |
| 35264460 | 2022 | CRISPR/Cas9-Mediated Insertion of HIV Long Terminal Repeat within BACH2 Promotes Expansion of T Regulatory-like Cells. | 5 |
| 35544467 | 2022 | Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients. | 2 |
| 36178457 | 2022 | BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis. | 5 |
| 33249782 | 2021 | Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus. | 6 |
| 33316352 | 2021 | Transcriptional behavior of the HIV-1 promoter in context of the BACH2 prominent proviral integration gene. | 3 |
| 33393145 | 2021 | BACH2-mediated FOS confers cytarabine resistance via stromal microenvironment alterations in pediatric ALL. | 3 |
Citation
Malene Krag Kjeldsen ; Karen Dybkaer ; Jinghua Liu ; Finn Skou Pedersen
BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2)
Atlas Genet Cytogenet Oncol Haematol. 2010-01-01
Online version: http://atlasgeneticsoncology.org/gene/741/bach2-(btb-and-cnc-homology-1-basic-leucine-zipper-transcription-factor-2)
