BTB and CNC homology 1 (BACH1) is a BTB-bZIP transcription factor of the CNC family that acts mainly as a heme-regulated transcriptional repressor. Through its bZIP domain it heterodimerizes with small Maf proteins (MAFK, MAFG, MAFF) and binds Maf recognition / antioxidant response elements (MARE/ARE) in RNA polymerase II enhancers, repressing genes of heme degradation, iron storage and export and redox defence (HMOX1, FTL, FTH1, SLC40A1, GCLM, SLC7A11) and, in macrophage precursors, the iron-recycling macrophage lineage factor SPIC; it antagonizes NRF2 (NFE2L2) at shared sites. Its N-terminal BTB domain mediates homodimerization and co-repressor recruitment. BACH1 is a direct heme sensor: heme binds cysteine-proline motifs in its C-terminal region, inhibits DNA binding, triggers CRM1-dependent nuclear export and promotes polyubiquitination and proteasomal degradation (SCF-FBXO22, SCF-FBXL17, and HOIL-1 in mouse cells), so rising heme derepresses its targets. Oxidative stress also releases it from chromatin and exposes BTB-domain degrons. In some cancer contexts BACH1 activates pro-metastatic genes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12511571 Bach1 functions as a hypoxia-inducible repressor for the hem... | ACCEPT | Summary: Kitamuro et al. 2003 show that BACH1 represses the human HMOX1 gene through a MARE that is required for hypoxia-induced repression. Reason: Repression of RNA polymerase II target genes (HMOX1, ferritins, SLC40A1, SPIC, GCLM, SLC7A11) through MARE/ARE elements, as a heterodimer with small Maf proteins, is the core biological role of BACH1, established in human cells and in Bach1-deficient mice. Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:24035498 Parallel SCF adaptor capture proteomics reveals a role for S... | ACCEPT | Summary: Tan et al. 2013 show that SCF-FBXL17 controls HMOX1 transcription through turnover of the repressor BACH1 in human cells. Reason: Repression of RNA polymerase II target genes (HMOX1, ferritins, SLC40A1, SPIC, GCLM, SLC7A11) through MARE/ARE elements, as a heterodimer with small Maf proteins, is the core biological role of BACH1, established in human cells and in Bach1-deficient mice. Supporting Evidence: PMID:24035498 FBXL17 controls the transcription of the NRF2 target HMOX1 via turnover of the transcriptional repressor BACH1 file:human/BACH1/BACH1-uniprot.txt Together with MAF, represses the transcription of genes under the control of the NFE2L2 oxidative stress pathway |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Bach1, the experimentally established Hmox1 repressor. Reason: Repression of RNA polymerase II target genes (HMOX1, ferritins, SLC40A1, SPIC, GCLM, SLC7A11) through MARE/ARE elements, as a heterodimer with small Maf proteins, is the core biological role of BACH1, established in human cells and in Bach1-deficient mice. Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:21555518 The BTB and CNC homology 1 (BACH1) target genes are involved... | ACCEPT | Summary: Warnatz et al. 2011 combined BACH1 ChIP-seq and three independent knockdowns in HEK293 cells; BACH1 targets were derepressed on knockdown. Reason: Repression of RNA polymerase II target genes (HMOX1, ferritins, SLC40A1, SPIC, GCLM, SLC7A11) through MARE/ARE elements, as a heterodimer with small Maf proteins, is the core biological role of BACH1, established in human cells and in Bach1-deficient mice. Supporting Evidence: PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | NAS PMID:33897412 Challenges and Limitations of Targeting the Keap1-Nrf2 Pathw... | ACCEPT | Summary: ComplexPortal NAS from a review describing BACH1 repression of NRF2 target genes at AREs. Reason: Repression of RNA polymerase II target genes (HMOX1, ferritins, SLC40A1, SPIC, GCLM, SLC7A11) through MARE/ARE elements, as a heterodimer with small Maf proteins, is the core biological role of BACH1, established in human cells and in Bach1-deficient mice. Supporting Evidence: PMID:33897412 Bach1 binds to ARE site present on the promoter to repress Nrf2 target genes. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based ISA assignment of chromatin location for a bZIP sequence-specific transcription factor. Reason: BACH1 occupies MARE-containing enhancers in chromatin (ChIP in mouse tissues and ChIP-seq in HEK293 cells) and is released from chromatin by heme or oxidative stress, so chromatin is where its repressor activity is exerted. Supporting Evidence: PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. PMID:39504958 FBXO22 recognizes a degron constructed by the BACH1 BTB domain dimer interface, which is unmasked from transcriptional co-repressors after oxidative stress releases BACH1 from chromatin. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT node PTN002918884, CNC/BACH clade) / Ensembl ortholog transfer of sequence-specific binding to Pol II cis-regulatory regions. Reason: BACH1-small Maf heterodimers bind MARE/ARE sites in HMOX1 enhancers and other Pol II target regulatory regions; heme inhibits this DNA binding. The CNC-bZIP clade placement is sound and BACH1 has no evidence of loss of DNA binding. Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo PMID:11387216 The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: IBA (PAINT node PTN002918884, CNC/BACH clade) / Ensembl ortholog transfer of sequence-specific binding to Pol II cis-regulatory regions. Reason: BACH1-small Maf heterodimers bind MARE/ARE sites in HMOX1 enhancers and other Pol II target regulatory regions; heme inhibits this DNA binding. The CNC-bZIP clade placement is sound and BACH1 has no evidence of loss of DNA binding. Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo PMID:11387216 The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | MODIFY | Summary: IBA (PTN002918884) and TFClass ISA assignment of Pol II-specific DNA-binding transcription factor activity. Reason: Correct, but BACH1's established activity is the more specific repressor child term GO:0001227, which the gene already carries by IDA (PMID:12511571, PMID:24035498). Context-dependent activation of pro-metastatic genes is a non-core addition, so the repressor term is the right refinement. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002918884 SUPPORTS TRANSFER CNC/BACH bZIP ancestral node; the general transcription-regulation term is sound for the clade, which includes activators (NFE2, NRF) and repressors (BACH). For BACH1 the experimentally supported refinement is repression, so the row is refined, not rejected. Proposed replacements: DNA-binding transcription repressor activity, RNA polymerase II-specific Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | MODIFY | Summary: IBA (PTN002918884) and TFClass ISA assignment of Pol II-specific DNA-binding transcription factor activity. Reason: Correct, but BACH1's established activity is the more specific repressor child term GO:0001227, which the gene already carries by IDA (PMID:12511571, PMID:24035498). Context-dependent activation of pro-metastatic genes is a non-core addition, so the repressor term is the right refinement. Proposed replacements: DNA-binding transcription repressor activity, RNA polymerase II-specific Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:12511571 Bach1 functions as a hypoxia-inducible repressor for the hem... | ACCEPT | Summary: BACH1 represses a human HMOX1 MARE reporter in human cells (Kitamuro et al. 2003). Reason: Core molecular function. BACH1 binds MAREs with MafK and represses Pol II target genes; heme relieves the repression. Supported in human cells and by the mouse knockout, in which Hmox1 is constitutively derepressed. Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:24035498 Parallel SCF adaptor capture proteomics reveals a role for S... | ACCEPT | Summary: BACH1 acts as the HMOX1 transcriptional repressor whose FBXL17-mediated turnover licenses NRF2 target activation (Tan et al. 2013). Reason: Core molecular function. BACH1 binds MAREs with MafK and represses Pol II target genes; heme relieves the repression. Supported in human cells and by the mouse knockout, in which Hmox1 is constitutively derepressed. Supporting Evidence: PMID:24035498 FBXL17 controls the transcription of the NRF2 target HMOX1 via turnover of the transcriptional repressor BACH1 file:human/BACH1/BACH1-uniprot.txt Together with MAF, represses the transcription of genes under the control of the NFE2L2 oxidative stress pathway |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Bach1. Reason: Core molecular function. BACH1 binds MAREs with MafK and represses Pol II target genes; heme relieves the repression. Supported in human cells and by the mouse knockout, in which Hmox1 is constitutively derepressed. Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of Pol II-specific transcription activator activity from mouse Bach1. Reason: BACH1 is predominantly a repressor, but it has been reported to activate transcription of pro-metastatic genes in lung cancer cells, and UniProt describes it as a repressor or activator depending on context. The activator role is context-specific and peripheral to the heme-regulated repressor function. Supporting Evidence: PMID:31257023 Bach1 promotes invasion and metastasis by activating the transcription of critical metastatic genes file:human/BACH1/BACH1-uniprot.txt Transcriptional regulator that acts as a repressor or activator, depending on the context. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: InterPro/ortholog-combined IEA for generic DNA binding (bZIP Maf / TF DNA-binding superfamily signatures). Reason: True but general. The DNA binding of BACH1 is sequence-specific binding to MARE/ARE elements in Pol II cis-regulatory regions, a term the gene already carries (IBA, IEA). Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo file:human/BACH1/BACH1-uniprot.txt Belongs to the bZIP family. CNC subfamily. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: Combined IEA from bZIP InterPro signatures and mouse ortholog. Reason: Correct but general. BACH1 is a Pol II-specific DNA-binding transcription repressor; the specific term GO:0001227 is already carried by IDA. Proposed replacements: DNA-binding transcription repressor activity, RNA polymerase II-specific Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse Bach1 (P97302). Reason: Correct but general. BACH1 is a Pol II-specific DNA-binding transcription repressor; the specific term GO:0001227 is already carried by IDA. Proposed replacements: DNA-binding transcription repressor activity, RNA polymerase II-specific Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:12356737 Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAFG (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAFG pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAF (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAF pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with ATF2 (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the ATF2 pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with ATF7 (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the ATF7 pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with DDIT3 (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the DDIT3 pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | REMOVE | Summary: In vitro coiled-coil array interaction with the Marek's disease virus bZIP oncoprotein MEQ. Reason: Bare protein binding is uninformative under the protein-binding policy, and the partner is an avian herpesvirus protein with no bearing on human BACH1 function. Removal does not assert that the in vitro interaction is false. Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAFB (Reinke et al. 2010). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAFB pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAFG (Reinke et al. 2013). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAFG pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with ATF2 (Reinke et al. 2013). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the ATF2 pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with DDIT3 (Reinke et al. 2013). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the DDIT3 pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAFF (Reinke et al. 2013). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAFF pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP coiled-coil interaction of BACH1 with MAFB (Reinke et al. 2013). Reason: Bare protein binding is uninformative. These coiled-coil array / in vitro dimerization assays measure leucine-zipper heterodimer formation between bZIP proteins, which is captured by protein heterodimerization activity. BACH1 functions as a heterodimer with small Maf proteins; the MAFB pairing is an assayed bZIP heterodimer. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Generic protein binding with MAFG from a quantitative AP-MS interactome (Hein et al. 2015). Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Generic protein binding with MAFF from a quantitative AP-MS interactome (Hein et al. 2015). Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding with MAFG from the BioPlex AP-MS interactome. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding with MAFF from the BioPlex AP-MS interactome. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein binding with PRKN isoform from a neurodegenerative-disease protein interactome screen. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein binding with VHL isoform from a neurodegenerative-disease protein interactome screen. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with MAFG from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with ATF2 from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with ATF7 from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with DYNLL1 from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. No follow-up study links DYNLL1 binding to a specific BACH1 molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with MAFF from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with MAFB from BioPlex 3.0 dual-cell-line AP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding with DYNLL1 from OpenCell endogenous-tag IP-MS. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. No follow-up study links DYNLL1 binding to a specific BACH1 molecular function. |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | REMOVE | Summary: Generic protein binding with DYNLL1 from a chromosome 21 protein-protein interaction screen. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. No follow-up study links DYNLL1 binding to a specific BACH1 molecular function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with MAFG from a multimodal cell-map interaction dataset. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with ATF2 from a multimodal cell-map interaction dataset. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with ATF7 from a multimodal cell-map interaction dataset. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with DYNLL1 from a multimodal cell-map interaction dataset. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. No follow-up study links DYNLL1 binding to a specific BACH1 molecular function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with MAFF from a multimodal cell-map interaction dataset. Reason: Bare protein binding is uninformative under the project protein-binding policy; this high-throughput interaction does not by itself establish a specific molecular function. Removal does not assert that the interaction is false. The BACH1-small Maf association is genuine and functionally central; it is captured by protein heterodimerization activity (from the in vitro bZIP dimerization data) and by the RNA polymerase II transcription regulator complex annotations. |
| GO:0005634 nucleus | HDA PMID:16780588 Cell array-based intracellular localization screening reveal... | ACCEPT | Summary: Cell-array localization screen of chromosome 21 proteins (colocalizes_with). Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. This overexpression screen saw BACH1 mainly cytosolic at interphase and near condensing chromatin in mitosis; the colocalizes_with nucleus row is consistent with nucleocytoplasmic shuttling. Supporting Evidence: PMID:16780588 At interphase, BACH1 was distributed in the entire cytosol. During the early phase of mitosis, however, the protein accumulated in the vicinity of condensing chromatin PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp... | ACCEPT | Summary: Dynamic proteomics (tagged protein imaging) in H1299 cells. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN002918884) nuclear activity across the CNC-bZIP clade. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | IDA PMID:12511571 Bach1 functions as a hypoxia-inducible repressor for the hem... | ACCEPT | Summary: Nuclear localization reported for BACH1 in human cells (Kitamuro et al. 2003). Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | IDA PMID:24035498 Parallel SCF adaptor capture proteomics reveals a role for S... | ACCEPT | Summary: Nuclear BACH1 reported by Tan et al. 2013; UniProt subcellular location cites this paper. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from UniProt subcellular location and ARBA. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | NAS PMID:1655749 The cAMP-regulated enhancer-binding protein ATF-1 activates ... | ACCEPT | Summary: ComplexPortal NAS; the cited paper is the ATF-1 cDNA characterization and does not mention BACH1. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. The cited reference (ATF-1 cDNA, 1991) does not support a BACH1 claim; the location is nevertheless correct and is accepted on independent evidence. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: ComplexPortal NAS for a BACH1-containing bZIP heterodimer complex. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005634 nucleus | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: ComplexPortal NAS for a BACH1-containing bZIP heterodimer complex. Reason: BACH1 is a nuclear transcription repressor that occupies MAREs on chromatin; heme triggers its CRM1-dependent export, so nuclear localization is regulated but is where the core activity occurs. Supporting Evidence: file:human/BACH1/BACH1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9707523 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9707523) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9707690 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9707690) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9707690 Transcription regulator protein BACH1 is a heterodimerization partner of MAFK PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708423 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708423) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708430 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708430) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708466 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708466) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708517 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708517) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708525 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708525) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708533 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708533) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708557 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9708557) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9762209 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9762209) placing BACH1 in the nucleoplasm in heme signalling / HMOX1 regulation reactions. Reason: BACH1 acts as a nucleoplasmic, chromatin-bound repressor with small Maf partners. Nucleoplasm is consistent with the nuclear localization evidence and with heme-regulated export from the nucleus. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005737 cytoplasm | HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp... | KEEP AS NON CORE | Summary: Dynamic proteomics (HDA) detection of tagged BACH1 in the cytoplasm. Reason: BACH1 shuttles: heme and oxidants trigger CRM1-dependent nuclear export and it is then degraded. Cytoplasmic presence is real but reflects inactivation/turnover, not the site of its function. Supporting Evidence: PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005829 cytosol | HDA PMID:16780588 Cell array-based intracellular localization screening reveal... | KEEP AS NON CORE | Summary: Cell-array overexpression screen: BACH1 distributed in the cytosol at interphase (colocalizes_with). Reason: Cytosolic BACH1 is the newly synthesized or heme/oxidant-exported, inactivated pool destined for proteasomal degradation. The location is real but peripheral to the repressor function. Supporting Evidence: PMID:16780588 At interphase, BACH1 was distributed in the entire cytosol. During the early phase of mitosis, however, the protein accumulated in the vicinity of condensing chromatin |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9708423 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-9708423) placing BACH1 in the cytosol (synthesis, heme/oxidant-induced export, re-import). Reason: Cytosolic BACH1 is the newly synthesized or heme/oxidant-exported, inactivated pool destined for proteasomal degradation. The location is real but peripheral to the repressor function. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9708466 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-9708466) placing BACH1 in the cytosol (synthesis, heme/oxidant-induced export, re-import). Reason: Cytosolic BACH1 is the newly synthesized or heme/oxidant-exported, inactivated pool destined for proteasomal degradation. The location is real but peripheral to the repressor function. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9708497 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-9708497) placing BACH1 in the cytosol (synthesis, heme/oxidant-induced export, re-import). Reason: Cytosolic BACH1 is the newly synthesized or heme/oxidant-exported, inactivated pool destined for proteasomal degradation. The location is real but peripheral to the repressor function. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9708533 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-9708533) placing BACH1 in the cytosol (synthesis, heme/oxidant-induced export, re-import). Reason: Cytosolic BACH1 is the newly synthesized or heme/oxidant-exported, inactivated pool destined for proteasomal degradation. The location is real but peripheral to the repressor function. Supporting Evidence: Reactome:R-HSA-9708423 Inhibition of heme synthesis enhances the nuclear accumulation of BACH1, whereas treating cells with hemin results in nuclear exclusion of BACH1. PMID:15175654 Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. |
| GO:0006281 DNA repair | IMP PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | REMOVE | Summary: IMP for DNA repair from Cantor et al. 2001, which characterizes the DEAH-box helicase BRCA1-associated C-terminal helicase 1, originally named BACH1 (now BRIP1/FANCJ, Q9BX63). Reason: Gene-product mis-attribution from a symbol collision. The cited abstract explicitly describes a DEAH helicase that binds BRCA1 BRCT repeats; O14867 is a BTB-bZIP transcription factor with no helicase domain. No evidence implicates the bZIP BACH1 in DNA repair. Supporting Evidence: PMID:11301010 BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. file:human/BACH1/BACH1-uniprot.txt Belongs to the bZIP family. CNC subfamily. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from bZIP signatures. Reason: Correct but general. BACH1 regulates RNA polymerase II genes and predominantly represses them; the specific term GO:0000122 is supported by IDA/IMP rows in this review. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0006355 regulation of DNA-templated transcription | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse Bach1 (P97302). Reason: Correct but general. BACH1 regulates RNA polymerase II genes and predominantly represses them; the specific term GO:0000122 is supported by IDA/IMP rows in this review. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | MODIFY | Summary: IBA (PTN002918884) regulation of Pol II transcription across the CNC-bZIP clade. Reason: True, but BACH1's documented direction of regulation is repression; GO:0000122 is carried by IDA and IMP in this review and is the appropriate refinement. The context-dependent activator role is captured separately as non-core. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002918884 SUPPORTS TRANSFER CNC/BACH bZIP ancestral node; the general transcription-regulation term is sound for the clade, which includes activators (NFE2, NRF) and repressors (BACH). For BACH1 the experimentally supported refinement is repression, so the row is refined, not rejected. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:1655749 The cAMP-regulated enhancer-binding protein ATF-1 activates ... | MODIFY | Summary: ComplexPortal NAS; the cited ATF-1 paper does not mention BACH1. Reason: True, but BACH1's documented direction of regulation is repression; GO:0000122 is carried by IDA and IMP in this review and is the appropriate refinement. The context-dependent activator role is captured separately as non-core. The cited reference itself does not concern BACH1. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: ComplexPortal NAS for BACH1-containing bZIP heterodimer complexes. Reason: True, but BACH1's documented direction of regulation is repression; GO:0000122 is carried by IDA and IMP in this review and is the appropriate refinement. The context-dependent activator role is captured separately as non-core. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: ComplexPortal NAS for BACH1-containing bZIP heterodimer complexes. Reason: True, but BACH1's documented direction of regulation is repression; GO:0000122 is carried by IDA and IMP in this review and is the appropriate refinement. The context-dependent activator role is captured separately as non-core. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12511571 We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. PMID:21555518 The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. |
| GO:0020037 heme binding | NAS PMID:21555518 The BTB and CNC homology 1 (BACH1) target genes are involved... | ACCEPT | Summary: NAS (UniProt) from Warnatz et al. 2011, which describes BACH1 as a heme-binding transcription factor. Reason: Heme binding is central to BACH1 biology: heme binds the C-terminal cysteine-proline motifs, inhibits DNA binding, triggers nuclear export and promotes polyubiquitination and degradation. Direct binding was shown biochemically by Ogawa et al. 2001. Supporting Evidence: PMID:21555518 BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels. PMID:11387216 Mutations in all of the CP motifs of Bach1 abolished its interaction with heme. PMID:11387216 The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of positive regulation of Pol II transcription from mouse Bach1. Reason: Context-dependent activation (pro-metastatic genes in lung cancer) has been reported, but BACH1's core role is repression; kept as non-core. Supporting Evidence: PMID:31257023 Bach1 promotes invasion and metastasis by activating the transcription of critical metastatic genes |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: ComplexPortal (IPI) membership in BACH1-small Maf bZIP heterodimer transcription regulator complexes. Reason: BACH1 binds DNA and represses transcription as a heterodimer with small Maf proteins (MAFK, MAFG, MAFF); these heterodimers are the functional unit of the repressor. Supporting Evidence: PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription PMID:20102225 using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: ComplexPortal (IPI) membership in BACH1-small Maf bZIP heterodimer transcription regulator complexes. Reason: BACH1 binds DNA and represses transcription as a heterodimer with small Maf proteins (MAFK, MAFG, MAFF); these heterodimers are the functional unit of the repressor. Supporting Evidence: PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs |
| GO:0090575 RNA polymerase II transcription regulator complex | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: ComplexPortal (NAS) membership in BACH1-small Maf bZIP heterodimer transcription regulator complexes. Reason: BACH1 binds DNA and represses transcription as a heterodimer with small Maf proteins (MAFK, MAFG, MAFF); these heterodimers are the functional unit of the repressor. Supporting Evidence: PMID:12356737 While Bach1 forms heterodimers with the small Maf proteins (as does Nrf2), the resulting Bach1 heterodimers repress MARE-dependent transcription PMID:23661758 quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs |
| GO:0098531 ligand-modulated transcription factor activity | IMP PMID:21555518 The BTB and CNC homology 1 (BACH1) target genes are involved... | ACCEPT | Summary: IMP (UniProt) from Warnatz et al. 2011 for ligand-modulated transcription factor activity. Reason: BACH1 is the archetypal heme-modulated mammalian transcription factor: heme binding to its CP motifs abolishes MARE binding and repression, analogous to the lac repressor (the GO definition's example). The Warnatz paper characterizes BACH1 targets by knockdown rather than testing heme modulation, but the claim is well supported by the heme-binding literature. Supporting Evidence: PMID:21555518 BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels. PMID:11387216 The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. PMID:12356737 regulation of ho-1 involves a direct sensing of heme levels by Bach1 (by analogy to lac repressor sensitivity to lactose) |
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Download this section (compressed HTML)Q: Which of the four (mouse) or corresponding human C-terminal cysteine-proline motifs are required for heme-induced FBXO22 versus FBXL17 recognition, and does heme act by unmasking BTB-domain degrons or by a separate heme-dependent E3 (HOIL-1/RBCK1)?
Q: Does BACH1 directly occupy the human SPIC locus in monocytes, and is heme-induced BACH1 degradation the rate-limiting step for human red pulp macrophage specification as in mouse?
Q: Is the reported activator function of BACH1 at pro-metastatic genes a direct DNA-binding activity (with which partner, and on which elements) or an indirect consequence of repressing other regulators?
Q: Should the CACAO DNA repair annotation from PMID:11301010 be moved from BACH1 (O14867) to BRIP1/FANCJ (Q9BX63), the helicase actually studied?
Experiment: CUT&RUN for BACH1 and MAFK in primary human monocytes with and without heme, combined with BACH1 CRISPR knockout and RNA-seq, to define the direct heme-derepressed target set (SPIC, HMOX1, SLC40A1) in human cells.
Experiment: Reconstitute heme-dependent ubiquitination of purified human BACH1 (wild type vs CP-motif mutants) with SCF-FBXO22, SCF-FBXL17 and LUBAC/HOIL-1 to determine which E3 directly reads the heme-bound state.
Experiment: Measure heme-binding stoichiometry and affinity of human BACH1 C-terminal region (UV-vis/resonance Raman, ITC) for each CP motif mutant to define the sensing threshold relative to labile heme concentrations.
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