BACH1 (human, O14867) curation notes

No deep-research provider output was available for this review (no provider API keys).
These notes were compiled manually from the cached UniProt record, the cached
publications under publications/, and Europe PMC searches. Every assertion below
carries its provenance.

Identity and architecture

• BTB-bZIP transcription regulator of the CNC subfamily; BTB/POZ domain (34-100) and
  bZIP domain (557-620) [file:human/BACH1/BACH1-uniprot.txt "Belongs to the bZIP family. CNC subfamily."].
• Heterodimerises with small Maf proteins (MAFK, MAFG, MAFF) and binds MARE/ARE
  elements PMID:12356737.
• The BTB domain mediates repression and homodimerisation; the bZIP mediates
  heterodimerisation PMID:24630724.

Heme sensing (primary papers verified in Europe PMC)

• Ogawa et al. 2001 EMBO J, PMID:11387216 (Europe PMC search "Ogawa Bach1 heme EMBO";
  title "Heme mediates derepression of Maf recognition element through direct binding to
  transcription repressor Bach1."). Heme binds the C-terminal cysteine-proline (CP) motifs
  and inhibits DNA binding PMID:11387216
  PMID:11387216
• Sun et al. 2002 EMBO J, PMID:12356737: Bach1 is the physiological repressor of
  Hmox1 in mice; heme inhibits its binding to the enhancers PMID:12356737.
• Suzuki et al. 2004 EMBO J, PMID:15175654: heme triggers CRM1-dependent nuclear export
  PMID:15175654
• Zenke-Kawasaki et al. 2007 Mol Cell Biol, PMID:17682061 (Europe PMC search
  "Zenke-Kawasaki ... Bach1"): heme induces polyubiquitination and degradation
  PMID:17682061
  HOIL-1 (RBCK1) proposed as an E3 PMID:17682061
• Lignitto et al. 2019 Cell, PMID:31257023: heme promotes FBXO22-mediated degradation
  PMID:31257023
• Cao et al. 2024 Cell, PMID:39504958: FBXO22 and FBXL17 recognise quaternary BTB degrons
  after oxidative stress releases BACH1 from chromatin
  PMID:39504958
• Tan et al. 2013 Mol Cell, PMID:24035498: SCF-FBXL17 turnover of BACH1 controls HMOX1
  PMID:24035498.

Most of the heme-binding/export/degradation biochemistry was done with mouse Bach1 or in
mouse cells; human-cell experiments include Suzuki 2004 (293T, GM02063) and Kitamuro 2003
(PMID:12511571, human HMOX1 repression).

Targets and biology

• Human HMOX1 repression via a MARE PMID:12511571
• ChIP-seq + knockdown in HEK293: HMOX1, FTL, FTH1, ME1, SLC48A1, GCLC, GCLM, SLC7A11 etc.
  PMID:21555518.
• Ferroportin (SLC40A1) is co-regulated with HMOX1 by heme via BACH1 at a MARE/ARE
  (PMID:20179090, abstract only, mouse RAW264.7).
• Spic repression in macrophage precursors: heme-induced proteasomal degradation of
  Bach1 de-represses Spic, driving red pulp / bone marrow iron-recycling macrophage
  development (mouse) PMID:24630724
  PMID:24630724
• Activator role: pro-metastatic genes in lung cancer PMID:31257023.

Annotation issues found

• GO:0006281 DNA repair (IMP, PMID:11301010, CACAO): the paper describes the DEAH helicase
  "BACH1" = BRIP1/FANCJ (UniProtKB:Q9BX63, gene names BRIP1 BACH1 FANCJ), not the bZIP
  BACH1. The abstract states "BRCA1 interacts in vivo with a novel protein, BACH1, a member
  of the DEAH helicase family." O14867 has no helicase domain. Recorded as a source defect
  (symbol collision).
• NAS rows from ComplexPortal citing PMID:1655749 (ATF-1 cDNA paper) do not mention BACH1;
  the claims (nucleus; regulation of Pol II transcription) are correct anyway.
• Protein-binding rows: bZIP coiled-coil array data (Reinke 2010, 2013) support
  leucine-zipper heterodimerisation with MAF/ATF/DDIT3 partners -> protein
  heterodimerization activity; AP-MS/Y2H rows removed per policy.
• Comparator/NEW: no NEW process terms proposed. "cellular response to heme" was
  considered; the guessed id turned out to be a different term (checked in QuickGO), and
  the existing ligand-modulated TF activity row already captures heme sensing.