BACH2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation placing BACH2 as a regulator of RNA Pol II transcription, inferred from phylogenetic analysis of the CNC-bZIP family. BACH2 is a well-established transcriptional regulator that binds MARE elements as a heterodimer with small MAF proteins and modulates Pol II-dependent gene expression in lymphocytes (PMID:28530713, PMID:27052415). Reason: This is a core function of BACH2. As a bZIP transcription factor, it directly regulates Pol II-dependent transcription. The IBA annotation is well supported by the phylogenetic relationship of BACH2 to other CNC-bZIP family members (NRF2, BACH1, NFE2L1) that all regulate Pol II transcription. The annotation is at the right level of generality for an IBA inference since BACH2 can act as both repressor and (in some contexts) activator. Supporting Evidence: PMID:17018862 we showed that Bach2 transcriptionally represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML PMID:28530713 BACH2 is a typical example of an SE-regulated gene associated with autoimmune disease. It is a highly conserved member of the basic and leucine zipper domain (bZIP) superfamily of TFs and a critical regulator of both T and B lymphocyte differentiation and maturation
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for sequence-specific DNA binding at Pol II cis-regulatory regions. BACH2 contains a bZIP DNA-binding domain (residues 646-709) and binds MARE motifs (TRE/CRE-like sequences with flanking TGC) as a heterodimer with small MAF proteins. This has been demonstrated by SELEX (PMID:28473536) and is consistent with its role as a sequence-specific DNA-binding transcription factor. Reason: BACH2 has a characterized bZIP DNA-binding domain and binds specific DNA sequences (MARE elements) at regulatory regions. The IBA annotation is phylogenetically consistent and directly supported by experimental evidence showing sequence-specific DNA binding via SELEX analysis (PMID:28473536). Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for DNA-binding transcription factor activity (Pol II-specific). BACH2 is a bona fide sequence-specific DNA-binding transcription factor that modulates Pol II transcription. It primarily acts as a transcriptional repressor, though it can also activate transcription in some contexts (UniProt, by similarity). Given BACH2's predominant repressor function, a more specific child term (GO:0001227, DNA-binding transcription repressor activity, RNA polymerase II-specific) would be more informative, but the parent term is not wrong. Reason: The IBA annotation is correct and at a reasonable level of specificity since the phylogenetic inference groups BACH2 with family members that can act as both activators and repressors. BACH2 is primarily a repressor but has been reported to also activate in some contexts, so the parent term GO:0000981 is defensible. Supporting Evidence: PMID:27052415 The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for generic DNA binding based on combined automated methods including InterPro domain matches (bZIP, bZIP_Maf) and orthology to mouse BACH2 (P97303). BACH2 does bind DNA through its bZIP domain, but this term is very general and is subsumed by the more specific annotations already present. Reason: While overly general, IEA annotations to broad parent terms are acceptable when more specific annotations exist. The more specific GO:0000978 (IBA) and GO:1990837 (IDA) already capture the DNA binding activity of BACH2 more precisely. This IEA annotation is not wrong and will be naturally superseded. Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for generic DNA-binding transcription factor activity based on InterPro domain matches and orthology. This is the parent of GO:0000981 which is already annotated via IBA. The annotation is correct but less specific. Reason: Correct but general. The more specific GO:0000981 (IBA) already captures the Pol II-specific transcription factor activity. This broader IEA term is acceptable as a computationally derived parent annotation.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for nuclear localization based on combined automated methods including orthology to mouse BACH2 and UniProt subcellular location data. BACH2 localizes to the nucleus where it functions as a transcriptional repressor. Nuclear localization is experimentally confirmed (PMID:17018862, PMID:28530713) and noted in UniProt. Reason: Correct. BACH2 functions in the nucleus as a transcription factor. UniProt confirms nuclear localization supported by experimental evidence from PMID:17018862 and PMID:28530713. BACH2 undergoes regulated nucleocytoplasmic shuttling, but the nucleus is a primary functional location. Supporting Evidence: PMID:17018862 Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization PMID:28530713 BACH2 dimers translocate to the nucleus where they interact with target DNA loci at palindromic Maf recognition elements (MARE), either alone or in collaboration with other members of the bZIP family, such as the small Maf proteins (MafF, MafG and MafK)
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for cytoplasmic localization based on UniProt subcellular location vocabulary mapping. UniProt lists cytoplasm as a subcellular location for BACH2, supported by experimental evidence showing that PI3K-AKT-dependent phosphorylation at Ser-521 promotes cytoplasmic accumulation (PMID:17018862). BACH2 also forms cytoplasmic aggregates when mutated (E788K variant in IMD60). Reason: Correct. BACH2 undergoes regulated nucleocytoplasmic shuttling. Phosphorylation at Ser-521 downstream of the PI3K pathway promotes cytoplasmic localization (PMID:17018862). The cytoplasm is a bona fide subcellular location for BACH2, particularly in its inactive/phosphorylated state. Supporting Evidence: PMID:17018862 Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization PMID:28530713 we found that wild-type BACH2 protein was evenly distributed in both cytoplasm and nucleus, whereas the E788K mutant protein was aggregated in the cytoplasm with relatively little in the nucleus
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for regulation of DNA-templated transcription based on InterPro domain associations (bZIP, bZIP_Maf, TF_DNA-bd domains). This is a parent term of GO:0006357 (regulation of transcription by RNA polymerase II) which is already annotated via IBA. Reason: Correct but more general than GO:0006357 already captured by IBA. As an IEA derived from domain associations, this broad annotation is acceptable and will be naturally superseded by the more specific annotations.
GO:0005515 protein binding	IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov...	MODIFY	Summary: IPI annotation for protein binding based on the Reinke et al. 2013 study that systematically measured bZIP dimerization networks across species. The with/from fields indicate interactions with MAFG (O15525), BATF3 (Q9NR55), and MAFF (Q9ULX9). These are biologically meaningful interactions: small MAF proteins are the canonical dimerization partners of BACH2 for DNA binding, and BATF3 is a bZIP family member. However, 'protein binding' is uninformative. Reason: The interactions with MAFG, MAFF, and BATF3 are biologically relevant dimerization events for a bZIP transcription factor. However, GO:0005515 (protein binding) is uninformative per GO curation guidelines. The actual function is DNA-binding transcription factor activity enabled by dimerization with small MAF proteins. The protein-protein interactions are integral to the transcription factor activity and are better captured by the ComplexPortal entries (CPX-2484 for BACH2-MAFF, CPX-2485 for BACH2-MAFG). Proposed replacements: protein homodimerization activity protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MODIFY	Summary: IPI annotation for protein binding based on BioPlex 2.0 high-throughput AP-MS study (Huttlin et al. 2017). The with/from fields include TULP3 (O75386), FOSL2 (P15408), BATF3 (Q9NR55), and MAFF (Q9ULX9). The interactions with FOSL2 (an AP-1 factor) and small MAFs are biologically meaningful for a bZIP TF, but TULP3 interaction is likely from high-throughput noise. Reason: High-throughput AP-MS data. Some interactors (FOSL2, BATF3, MAFF) are biologically plausible bZIP dimerization partners. Others (TULP3) may be spurious. GO:0005515 is uninformative per curation guidelines. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome	MODIFY	Summary: IPI annotation for protein binding based on the HuRI reference binary interactome study (Luck et al. 2020). This study identified numerous interaction partners including MAFG (O15525), MAFK (O60675), FOSL2 (P15408), BATF3 (Q9NR55), and many other proteins. The MAF/BATF3 interactions are biologically meaningful as canonical bZIP dimerization partners. Many others (CTSZ, CENPP, CFAP58, etc.) are likely high-throughput artifacts. Reason: Large-scale binary interactome study. GO:0005515 is uninformative. The meaningful interactions (with MAF proteins and bZIP family members) reflect heterodimerization activity integral to transcription factor function. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: IPI annotation for protein binding based on BioPlex 3.0 (Huttlin et al. 2021). Interactors include MAFG (O15525), MAFK (O60675), MAFF (Q9ULX9), FOSL2 (P15408), BATF3 (Q9NR55), ZBTB24, and ZBTB34. The MAF interactions are canonical and biologically validated. Reason: Proteome-scale interactome study. GO:0005515 is uninformative per curation guidelines. The biologically meaningful interactions are bZIP dimerization with small MAFs and other bZIP family members. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MODIFY	Summary: IPI annotation for protein binding from multimodal cell maps study (Schaffer et al. 2025). The with/from field indicates interaction with MAFK (O60675), a canonical small MAF dimerization partner of BACH2. Reason: GO:0005515 is uninformative. The MAFK interaction is a canonical bZIP heterodimerization that is integral to BACH2's transcription factor function. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics
GO:0000122 negative regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog (P97303) via Ensembl Compara. BACH2 is well established as a transcriptional repressor. It represses PRDM1 (Blimp-1) to maintain germinal center programs in B cells, and represses effector gene programs (Gata3, Irf4, Prdm1, Gzmb) in T cells. The mouse ortholog has extensive experimental evidence for transcriptional repression. Reason: Correct and central to BACH2 biology. BACH2 is predominantly a transcriptional repressor. PMID:17018862 shows repression of HMOX1, and PMID:28530713 shows BACH2 represses PRDM1 to control B cell differentiation. This IEA from Ensembl Compara is well supported by the biology. Supporting Evidence: PMID:17018862 we showed that Bach2 transcriptionally represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML PMID:28530713 In B cells, BACH2 controls the balance between Pax5 and Blimp1 by repressing the latter
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog via Ensembl Compara. Duplicates the IBA annotation for the same term. BACH2 does bind DNA in a sequence-specific manner at Pol II-regulated genes. Reason: Correct and consistent with the IBA annotation for the same term. Duplication of evidence from different sources (IBA and IEA) is normal and acceptable.
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for transcription repressor activity transferred from mouse ortholog via Ensembl Compara. This is the most specific and accurate molecular function term for BACH2, which primarily functions as a DNA-binding transcriptional repressor at MARE elements in Pol II-transcribed genes. Reason: This is the most accurate MF term for BACH2's primary molecular function. BACH2 predominantly represses transcription by binding MARE elements as a heterodimer with small MAF proteins. It represses PRDM1/Blimp-1 in B cells and effector gene programs in T cells. Per GO TF annotation guidelines, a child of GO:0000981 specifying repressor activity is the ideal annotation for a predominantly repressive DNA-binding transcription factor. Supporting Evidence: PMID:17018862 we showed that Bach2 transcriptionally represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML PMID:28530713 BACH2 acts as a repressive "guardian" TF that regulates the balance between a network of other TFs critical to T and B cell specification and maturation
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation for nucleoplasm localization based on HPA immunofluorescence data curation. BACH2 functions in the nucleoplasm as a transcription factor. When in the nucleus, it would be expected to be in the nucleoplasm where it accesses chromatin and regulatory DNA elements. Reason: Correct. BACH2 is a transcription factor that functions in the nucleoplasm. IDA from HPA immunofluorescence is appropriate evidence for subcellular localization.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation for cytosol localization based on HPA immunofluorescence data. BACH2 is known to undergo regulated nucleocytoplasmic shuttling, with PI3K-AKT-dependent phosphorylation at Ser-521 promoting cytoplasmic accumulation (PMID:17018862). The cytosol is a bona fide localization for the inactive/phosphorylated form. Reason: Correct. BACH2 accumulates in the cytoplasm/cytosol when phosphorylated by the PI3K-AKT pathway. This is more specific than GO:0005737 (cytoplasm) already annotated via IEA. HPA immunofluorescence data supports this. Supporting Evidence: PMID:17018862 Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization
GO:0000122 negative regulation of transcription by RNA polymerase II	NAS PMID:27052415 The Bach Family of Transcription Factors: A Comprehensive Re...	ACCEPT	Summary: NAS annotation from ComplexPortal for negative regulation of Pol II transcription, citing PMID:27052415 (Zhou et al. 2016). This review describes how BACH2 represses target gene expression by forming heterodimers with small Maf proteins. BACH2's primary role as a transcriptional repressor is well documented across multiple studies. Reason: Correct and well supported. PMID:27052415 is a comprehensive review of the Bach family of transcription factors that clearly describes BACH2 as repressing target gene expression. The same term is also annotated via IEA from Ensembl Compara. Both annotations are correct for this core function of BACH2. Supporting Evidence: PMID:27052415 The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins
GO:0005634 nucleus	NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov...	ACCEPT	Summary: NAS annotation from ComplexPortal for nuclear localization, citing the Reinke et al. 2013 bZIP network study. This study characterized bZIP protein-protein interactions in vitro and does not directly demonstrate nuclear localization. However, nuclear localization is well established for BACH2 from other studies. Reason: Nuclear localization of BACH2 is well supported by multiple lines of evidence (PMID:17018862, PMID:28530713, UniProt subcellular location). The NAS evidence code from ComplexPortal is acceptable since BACH2 functions as a nuclear transcription factor in complex with MAF proteins. Supporting Evidence: PMID:28530713 BACH2 dimers translocate to the nucleus where they interact with target DNA loci at palindromic Maf recognition elements (MARE), either alone or in collaboration with other members of the bZIP family, such as the small Maf proteins (MafF, MafG and MafK)
GO:0005634 nucleus	NAS PMID:27052415 The Bach Family of Transcription Factors: A Comprehensive Re...	ACCEPT	Summary: NAS annotation from ComplexPortal for nuclear localization, citing PMID:27052415 (Zhou et al. 2016). This review confirms BACH2 is a nuclear transcription factor that represses gene expression. Reason: Correct. Nuclear localization is well established for BACH2 as a transcription factor. PMID:27052415 describes BACH2 as a transcription factor that represses target gene expression, which requires nuclear localization. This is consistent with the other nuclear localization annotations from IEA, NAS, and IDA evidence. Supporting Evidence: PMID:27052415 The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins
GO:0006357 regulation of transcription by RNA polymerase II	NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov...	ACCEPT	Summary: NAS annotation from ComplexPortal for regulation of Pol II transcription, citing the Reinke et al. 2013 bZIP dimerization study. The study demonstrated BACH2 forms heterodimers with small MAF proteins and other bZIP factors, consistent with regulation of Pol II transcription. This is a duplicate of the IBA annotation for the same term. Reason: Correct. BACH2 regulates Pol II transcription as a bZIP transcription factor. The NAS evidence from ComplexPortal is based on the bZIP dimerization data. Same term already captured by IBA with stronger phylogenetic evidence. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ...	ACCEPT	Summary: IDA annotation for sequence-specific double-stranded DNA binding based on Yin et al. 2017, a systematic SELEX study of 542 human TFs. BACH2 was among the TFs tested, and its binding specificities to double-stranded DNA sequences were characterized. This directly demonstrates BACH2 binds specific dsDNA sequences. Reason: Strong experimental evidence (IDA from SELEX) directly demonstrating that BACH2 binds specific dsDNA sequences. This is consistent with BACH2's bZIP domain and its function as a sequence-specific DNA-binding transcription factor that recognizes MARE motifs. Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences
GO:0090721 primary adaptive immune response involving T cells and B cells	IMP PMID:28530713 BACH2 immunodeficiency illustrates an association between su...	KEEP AS NON CORE	Summary: IMP annotation for involvement in primary adaptive immune response based on Afzali et al. 2017, which characterized human BACH2 haploinsufficiency (BRIDA/IMD60). Patients with heterozygous BACH2 variants showed impaired lymphocyte maturation, decreased immunoglobulin production, and autoimmunity, demonstrating BACH2 is essential for proper adaptive immune responses. Reason: While BACH2 is clearly required for proper adaptive immune function (as demonstrated by the BRIDA phenotype), this is a very broad biological process term that describes the downstream consequence of BACH2's transcriptional repressor activity rather than its core molecular function. The primary role of BACH2 is as a DNA-binding transcriptional repressor; its involvement in adaptive immunity is a downstream effect of that core function in lymphocytes. Marking as non-core since the annotation is correct but represents a broad organismal phenotype rather than a core molecular-level function. Supporting Evidence: PMID:28530713 Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency
GO:0000785 chromatin	ISA GO_REF:0000113	ACCEPT	Summary: ISA annotation for chromatin localization based on TFClass database annotation of BACH2 as a sequence-specific DNA-binding transcription factor (class 1.1.1, basic leucine zipper factors / Jun-related). TFClass classification places BACH2 as a DNA-binding TF expected to localize to chromatin when bound to DNA. Reason: Correct. As a DNA-binding transcription factor, BACH2 localizes to chromatin where it binds MARE elements. ChIP-seq studies in lymphocytes have mapped BACH2 binding across the genome. The ISA inference from TFClass classification is sound.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISA GO_REF:0000113	ACCEPT	Summary: ISA annotation for DNA-binding transcription factor activity based on TFClass database classification (class 1.1.1). This duplicates the IBA annotation for the same term. TFClass independently confirms BACH2 as a bona fide DNA-binding transcription factor. Reason: Correct and consistent with the IBA annotation. TFClass independently classifies BACH2 as a DNA-binding transcription factor (basic leucine zipper factor class). Duplicate annotations from independent evidence sources are acceptable.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

📄 View Raw YAML