Aliases for ATF4 Gene
- Activating Transcription Factor 4 2 3 4 5
- CREB-2 2 3 4
- Tax-Responsive Enhancer Element-Binding Protein 67 3 4
- Cyclic AMP-Dependent Transcription Factor ATF-4 3 4
- Cyclic AMP-Responsive Element-Binding Protein 2 3 4
- CAMP-Dependent Transcription Factor ATF-4 3 4
- CAMP-Responsive Element-Binding Protein 2 3 4
- Tax-Responsive Enhancer Element B67 2 3
External Ids for ATF4 Gene
Previous HGNC Symbols for ATF4 Gene
Previous GeneCards Identifiers for ATF4 Gene
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]
GeneCards Summary for ATF4 Gene
ATF4 (Activating Transcription Factor 4) is a Protein Coding gene. Diseases associated with ATF4 include Coffin-Lowry Syndrome and Leukoencephalopathy With Vanishing White Matter. Among its related pathways are Apoptosis Modulation and Signaling and Pathways of neurodegeneration - multiple diseases. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is ATF5.
UniProtKB/Swiss-Prot Summary for ATF4 Gene
Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and acts both as a regulator of normal metabolic and redox processes, and as a master transcription factor during the integrated stress response (ISR) (PubMed:1847461, PubMed:16682973, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress, such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:32132707). During the ISR, ATF4 protein is translated in response to eIF-2-alpha/EIF2S1 phosphorylation caused by stress, and acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:32132707). Protects cells against metabolic consequences of ER oxidation by promoting expression of genes linked to amino acid sufficiency and resistance to oxidative stress (By similarity). Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to amino acid deprivation or endoplasmic reticulum (ER) stress (PubMed:11960987). Together with DDIT3/CHOP, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). ATF4 and DDIT3/CHOP activate the transcription of TRIB3 and promote ER stress-induced neuronal cell-death by regulating the expression of BBC3/PUMA (PubMed:15775988, PubMed:18940792). During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed:26086088). Activates expression of genes required to promote cell recovery in response to mitochondrial stress (PubMed:32132706, PubMed:32132707). Independently of the ISR, also required for normal metabolic processes: plays a key role in embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471).
(Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I.