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FLASH GENE

Symbol

BACH1

contributors: mct - updated : 03-10-2016

HGNC name	BTB and CNC homology 1, basic leucine zipper transcription factor 1
HGNC id	935

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	anonymous DNA segment
STRUCTURE	63.10 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D21S190 - D21S298 - D21S260 - D21S226 - D21S1442 - BACH1 - D21S213 - D21S262 - D21S404 - qter
Text	see GRIK1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_206866 5 - 5770 NP_996749 32 736 - 1998 9479503 also called variant 1 variant 3 - - 2743 isoform 3 - 623 . ubiquitous, highly in testis . nuclear 2001 11069897 also called BACH1-T lacking the C terminal leucine zipper domain NM_001186 5 - 5642 NP_001177 82 736 - 2001 11069897 also called variant 2

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel         Homo sapiens Endocrine adrenal gland       highly Reproductive male system testis     highly Respiratory respiratory tract trachea     highly

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal BTB (broad complex-tamtrack-bric-a-brac) domain, that is thought to contribute to DNA binding through oligomerization with neighboring BACH1 heterodimers to stabilize their interactions with DNA
	POZ (pox virus and zinc finger) protein interaction domain
	a C terminal basic leucine zipper (bZIP) of the cap'n'collar type, and is also excluded from mitotic chromatin by a C-terminal cytoplasmic localization sequence dependent and leptomycin B sensitive process

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

homolog to murine Bac-1 transcription factor

Homologene

FAMILY	DEAH helicase family
	bZIP family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	predominantly localized to the nucleus of control cells
	despite its role in transcription, is predominantly exported to the cytoplasm in a XPO1-dependent manner

basic FUNCTION	activator in cultured erythroid cells
	transcription repressor in fibroblasts
	hematopoietic transcription factor implicated in megakaryocytes differentiation
	having a specific and selective ability to repress expression of hepatic HMOX1
	heme-regulated repressor of alpha-globin genes, playing a role in redox induction of HMOX1 and NQO1, though the exact mechanism of this repression is not clear
	confers an additional level of regulation to ARE-dependent genes that reveals a new dimension to the oxidative stress response
	may serve to not only facilitate DNA repair, but also maintain BRCA1 in DNA damage foci
	may function as a rheostat regulating levels of intracellular free heme
	acts as a relatively specific transcription factor, as judged by the small number of target regions compared with other bZIP transcription factors for which up to several thousands of peaks have been observed
	plays a specific role in sensing and regulating HMOX-dependent heme turnover and maintains intracellular heme homeostasis by functioning as a fulcrum that balances intracellular heme levels with cellular redox status through the expression of HMOX1
	repressor of the oxidative stress response
	inhibits oxidative stress-inducible genes, and is a crucial negative regulator of oxidative stress–induced cellular senescence
	connects oxygen metabolism and cellular senescence as a negative regulator of TP53
	TOPBP1 and BACH1 are required for ATR-dependent phosphorylation events in response to replication stress
	plays a critical role in regulating HMOX1 gene expression in acute myeloid leukemia cells and its expression suppresses their
	survival by downregulating HMOX1 expression
	in response to oxidative stress, regulates the oxidation state through the negative control of heme oxygenase-1 expression prior to terminal keratinocyte differentiation
	its function may affect not only the pathogenesis of skin diseases but also the process of skin aging
	heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels
	is a repressor of the oxidative stress response, and a negative regulator of ROS-induced cellular senescence directed by TP53
	is the master regulator of breast cancer bone metastasis
	heme may regulate BACH1 as an extracellular signaling molecule
	BACH2 functions with BACH1 and EBF1 to promote B cell development by repressing myeloid genes in common lymphoid progenitor (CLP) (
	regulates genes involved in the oxidative stress response and cell-cycle progression
	suppresses cell proliferation and induces cell-cycle arrest and apoptosis by increasing mitochondrial ROS production
	acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative
	BACH1 and BACH2 work in a complementary manner to maintain the normal function of the alveolar macrophages (AMs) and surfactant homeostasis in the lung

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	heterodimer with MAFK
	forms a heterodimer with the small Maf oncoproteins and binds to the Maf-recognition element (MARE) to inhibit target genes, including HMOX1
	bound to the ARE enhancer motifs preventing NFE2L2 from binding and thereby repressing transcription
	complex with TP53 on a subset of its target genes to restrain the transcriptional activity of TP53 by recruiting histone deacetylase 1 (HDAC1), thus inhibiting the process of cellular senescence
	novel role of BACH1 in the regulation of mitotic chromosome dynamics

INTERACTION

DNA

RNA

small molecule

protein	binding NF-E2 binding sites with MAFK coordinating transcription activation and repression by MAFK
	binding directly to BRCT repeats of BRCA1 and contributing to its activity
	interacting with NFE2L2, bound to the ARE enhancer motifs preventing NFE2L2 from binding and thereby
	binds HMOX1 antioxidant response elements and represses transcription
	repressing transcription (dynamic roles of BACH1 and NFE2L2 in the transcription of the heme oxygenase-1 (HMOX1) gene)
	interacts directly with the BRCA1 C-terminal BRCT repeats, which are important for BRCA1 DNA repair
	increased expression of the BACH1 target sequestosome 1 (SQSTM1), a multifunctional ubiquitin-binding protein that serves as a storage place for ubiquitinated protein
	specific interaction between TOPBP1 and BACH1/FANCJ, a DNA helicase involved in the repair of DNA crosslinks
	key player in the physiological regulation of oxidative stress, where it acts as a repressor of its main target, HMOX1
	PSAP and MAPT are direct BACH1 target genes, both of which have been identified as potential biomarkers for the detection of Alzheimer disease
	the CDKN2A-BACH1 interaction constitutes a regulatory pathway of TP53 in parallel with the CDKN2A-MDM2 pathway
	critical role of BACH1 in cell transformation and tumor growth induced by activated HRAS
	TGFB1 induced expression of transcription factors MAFK and BACH1
	suppresses angiogenesis after ischemic injury and impairs Wnt/CTNNB1 signaling by disrupting the interaction between CTNNB1 and TCF4
	transcriptional repressor of Heme oxygenase-1 (HO-1), which is cytoprotective through its antioxidant effects
	HOXB8 interacted with a key metastasis regulator BACH1 and instigated BACH1-mediated transcriptional cascade by directly occupying and activating BACH1 gene transcription together with BACH1 itself

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in acute megakaryoblastic leukemia

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   promising treatment target for the treatment of vascular diseases cancer hemopathy   functional upregulation of BACH1 is a potential strategy for antileukemic therapy immunology autoimmune articular inactivation of BACH11 is a novel target and signaling pathway in OA prevention

ANIMAL & CELL MODELS