Human Gene ATF4 (ENST00000337304.2) Description and Page Index
Description: Homo sapiens activating transcription factor 4 (ATF4), transcript variant 1, mRNA. (from RefSeq NM_001675) RefSeq Summary (NM_001675): 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]. Gencode Transcript: ENST00000337304.2 Gencode Gene: ENSG00000128272.14 Transcript (Including UTRs) Position: hg38 chr22:39,520,564-39,522,683 Size: 2,120 Total Exon Count: 2 Strand: + Coding Region Position: hg38 chr22:39,521,446-39,522,602 Size: 1,157 Coding Exon Count: 2
ID:ATF4_HUMAN DESCRIPTION: RecName: Full=Cyclic AMP-dependent transcription factor ATF-4; Short=cAMP-dependent transcription factor ATF-4; AltName: Full=Activating transcription factor 4; AltName: Full=Cyclic AMP-responsive element-binding protein 2; Short=CREB-2; Short=cAMP-responsive element-binding protein 2; AltName: Full=DNA-binding protein TAXREB67; AltName: Full=Tax-responsive enhancer element-binding protein 67; Short=TaxREB67; FUNCTION: Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to ER stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. SUBUNIT: Binds DNA as a homo- or heterodimer. Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C- termini). Interacts (via its DNA binding domain) with FOXO1 (C- terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production. Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (By similarity). Interacts with CEP290 (via an N-terminal region). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3. Forms a heterodimer with TXLNG in osteoblasts. Interacts with DDIT3/CHOP. INTERACTION: Q9NRI5:DISC1; NbExp=3; IntAct=EBI-492498, EBI-529989; Q96RU7:TRIB3; NbExp=2; IntAct=EBI-492498, EBI-492476; SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Nucleus. Cytoplasm, cytoskeleton, centrosome. Note=Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Co- localizes with NEK6 in the centrosome. PTM: Phosphorylated by NEK6. SIMILARITY: Belongs to the bZIP family. SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P18848
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001085 RNA polymerase II transcription factor binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor binding GO:0019901 protein kinase binding GO:0043522 leucine zipper domain binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0046982 protein heterodimerization activity
Biological Process: GO:0006094 gluconeogenesis GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006520 cellular amino acid metabolic process GO:0007214 gamma-aminobutyric acid signaling pathway GO:0007623 circadian rhythm GO:0009636 response to toxic substance GO:0010575 positive regulation of vascular endothelial growth factor production GO:0010628 positive regulation of gene expression GO:0030182 neuron differentiation GO:0032057 negative regulation of translational initiation in response to stress GO:0032922 circadian regulation of gene expression GO:0034198 cellular response to amino acid starvation GO:0034644 cellular response to UV GO:0034976 response to endoplasmic reticulum stress GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress GO:0036091 positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0036499 PERK-mediated unfolded protein response GO:0042149 cellular response to glucose starvation GO:0042789 mRNA transcription from RNA polymerase II promoter GO:0043065 positive regulation of apoptotic process GO:0043267 negative regulation of potassium ion transport GO:0043525 positive regulation of neuron apoptotic process GO:0045893 positive regulation of transcription, DNA-templated GO:0045943 positive regulation of transcription from RNA polymerase I promoter GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0061395 positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0090650 cellular response to oxygen-glucose deprivation GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1903204 negative regulation of oxidative stress-induced neuron death GO:1903351 cellular response to dopamine GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990737 response to manganese-induced endoplasmic reticulum stress