ATF4 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0006366Biological processtranscription by RNA polymerase II
GO_1990253Biological processcellular response to leucine starvation
GO_1903377Biological processnegative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO_0045667Biological processregulation of osteoblast differentiation
GO_0006874Biological processintracellular calcium ion homeostasis
GO_0042789Biological processmRNA transcription by RNA polymerase II
GO_1990737Biological processresponse to manganese-induced endoplasmic reticulum stress
GO_0034644Biological processcellular response to UV
GO_0034976Biological processresponse to endoplasmic reticulum stress
GO_0006357Biological processregulation of transcription by RNA polymerase II
GO_0010628Biological processpositive regulation of gene expression
GO_0140468Biological processHRI-mediated signaling
GO_0030968Biological processendoplasmic reticulum unfolded protein response
GO_0030182Biological processneuron differentiation
GO_0006355Biological processregulation of DNA-templated transcription
GO_0035162Biological processembryonic hemopoiesis
GO_0042149Biological processcellular response to glucose starvation
GO_0070059Biological processintrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO_2000120Biological processpositive regulation of sodium-dependent phosphate transport
GO_0070169Biological processpositive regulation of biomineral tissue development
GO_0036499Biological processPERK-mediated unfolded protein response
GO_0034599Biological processcellular response to oxidative stress
GO_0045893Biological processpositive regulation of DNA-templated transcription
GO_0045943Biological processpositive regulation of transcription by RNA polymerase I
GO_0043267Biological processnegative regulation of potassium ion transport
GO_0010575Biological processpositive regulation of vascular endothelial growth factor production
GO_0009636Biological processresponse to toxic substance
GO_0043065Biological processpositive regulation of apoptotic process
GO_0032057Biological processnegative regulation of translational initiation in response to stress
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0120163Biological processnegative regulation of cold-induced thermogenesis
GO_1905461Biological processpositive regulation of vascular associated smooth muscle cell apoptotic process
GO_0070982Biological processL-asparagine metabolic process
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0032922Biological processcircadian regulation of gene expression
GO_0043525Biological processpositive regulation of neuron apoptotic process
GO_0031667Biological processresponse to nutrient levels
GO_0048167Biological processregulation of synaptic plasticity
GO_0006094Biological processgluconeogenesis
GO_0070309Biological processlens fiber cell morphogenesis
GO_0030282Biological processbone mineralization
GO_0034198Biological processcellular response to amino acid starvation
GO_0007214Biological processgamma-aminobutyric acid signaling pathway
GO_0140467Biological processintegrated stress response signaling
GO_0071456Biological processcellular response to hypoxia
GO_1990617Cellular componentCHOP-ATF4 complex
GO_0043005Cellular componentneuron projection
GO_0005634Cellular componentnucleus
GO_1990589Cellular componentATF4-CREB1 transcription factor complex
GO_0005654Cellular componentnucleoplasm
GO_1990037Cellular componentLewy body core
GO_1990590Cellular componentATF1-ATF4 transcription factor complex
GO_0034399Cellular componentnuclear periphery
GO_0032590Cellular componentdendrite membrane
GO_0005813Cellular componentcentrosome
GO_0032991Cellular componentprotein-containing complex
GO_0090575Cellular componentRNA polymerase II transcription regulator complex
GO_0005737Cellular componentcytoplasm
GO_0000785Cellular componentchromatin
GO_0016607Cellular componentnuclear speck
GO_0005829Cellular componentcytosol
GO_0001228Molecular functionDNA-binding transcription activator activity, RNA polymerase II-specific
GO_0042802Molecular functionidentical protein binding
GO_0046982Molecular functionprotein heterodimerization activity
GO_0008140Molecular functioncAMP response element binding protein binding
GO_0000978Molecular functionRNA polymerase II cis-regulatory region sequence-specific DNA binding
GO_1990841Molecular functionpromoter-specific chromatin binding
GO_0043565Molecular functionsequence-specific DNA binding
GO_0043522Molecular functionleucine zipper domain binding
GO_0061629Molecular functionRNA polymerase II-specific DNA-binding transcription factor binding
GO_0140296Molecular functiongeneral transcription initiation factor binding
GO_0000976Molecular functiontranscription cis-regulatory region binding
GO_0003700Molecular functionDNA-binding transcription factor activity
GO_0005515Molecular functionprotein binding
GO_0003677Molecular functionDNA binding
GO_0000977Molecular functionRNA polymerase II transcription regulatory region sequence-specific DNA binding
GO_0000981Molecular functionDNA-binding transcription factor activity, RNA polymerase II-specific
GO_1990837Molecular functionsequence-specific double-stranded DNA binding
GO_0019901Molecular functionprotein kinase binding

IV. Literature review

[source]
Gene nameATF4
Protein nameCyclic AMP-dependent transcription factor ATF-4 (Activating transcription factor 4)
Cyclic AMP-dependent transcription factor ATF-4 (cAMP-dependent transcription factor ATF-4) (Activating transcription factor 4) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (Tax-responsive enhancer element-binding protein 67) (TaxREB67)
Cyclic AMP-dependent transcription factor ATF-4
Activating transcription factor 4
SynonymsTXREB
CREB2
DescriptionFUNCTION: Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) . 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 . During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery . Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress . Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress . However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation . Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress . May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress . In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as 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 . 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 . .; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. .

AccessionsENST00000680748.1
ENST00000674835
ENST00000676346
ENST00000674920.3
A0A6Q8PGY1
ENST00000680446.1
A0A6Q8PFH6
ENST00000676346.2
ENST00000404241.6
P18848
A0A6Q8PG17
ENST00000674835.2
ENST00000396680.3
Q6ICP0
ENST00000674568.2
ENST00000675582.2
ENST00000674568
ENST00000679776.1
ENST00000337304.2
B4DJD4
A0A6Q8PHB3
A0A7P0Z4J5