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ATF4 (activating transcription factor 4 (tax-responsive enhancer element B67))

Written2009-10Kurosh Ameri, Adrian L Harris
Stanford University School of Medicine, Department of Surgery, Medical School Lab Surge Building 1201 Welch Road, Stanford, CA 94305, USA (KA); University of Oxford, Cancer Research UK, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK (ALH)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesTXREB
activating transcription factor 4 (tax-responsive enhancer element B67)
Alias_symbol (synonym)TAXREB67
CREB-2
Other aliasCREB2
HGNC (Hugo) ATF4
LocusID (NCBI) 468
Atlas_Id 44413
Location 22q13.1  [Link to chromosome band 22q13]
Location_base_pair Starts at 39916564 and ends at 39918691 bp from pter ( according to hg19-Feb_2009)  [Mapping ATF4.png]
Fusion genes
(updated 2016)
ATF4 (22q13.1) / CDV3 (3q22.1)ATF4 (22q13.1) / ZDHHC7 (16q24.1)LINC00312 (3p26.1) / ATF4 (22q13.1)
PARG (10q11.23) / ATF4 (22q13.1)
Note ATF4 has a genomic size of 2122.bp
The mouse ATFx has been classified as a member of the ATF4 subgroup due to 55% identity to mATF4.

DNA/RNA

Note ATF4 gene is transcribed at very high levels (according to ACEview). Several stress conditions such as hypoxia, anoxia, and glucose deprivation result in endoplasmic reticulum stress (ER stress), initiating the unfolded protein response pathway (UPR pathway) that increases the synthesis (increased mRNA translation) of ATF4.
 
Description The mouse ATF4 mRNA contains two upstream open reading frames, uORF1 and uORF2, and the human ATF4 contains three open reading frames, uORF1 (uO1), uORF2 (uO2), and uORF3 (uO3) that are located 5' to the ATF4 coding sequence. These uORFs are translated in non-stressed conditions, which result in exclusion of ATF4 translation. In mouse, uORF2, or in humans, uORF3 overlap ATF4 ORF in an out of frame manner. After translation of uORF1, sufficient eIF2-GTP makes it possible to reinitiate translation from the uORF2 in mouse, and uORF3 in human, and therefore ATF4 synthesis is minimized. During ER stress, PERK phosphorylates eIF2alpha resulting in a decrease of functional eIF2 complex. Stress-induced p-elF2alpha leads to limited eIF2-GTP and prolongs the duration for the scanning ribosome to reinitiate following uORF1, 2, and 3. Consequently ribosome scanning bypasses the mouse uORF2 or human uORF3, and translation re-initiation occurs at the ATF4 ORF (initiation at the ATF4 coding region is increased). Therefore, translation of ATF4 is increased in response to stress including hypoxia, anoxia, nutrition deprivation, including amino acid limitation and glucose deprivation.

Protein

Note ATF4 protein consists of 351 amino acids and is 38,590 Da. The protein is structured into several domains/motifs.
 
Description ATF4 protein consists of 351 amino acids. The protein is unstable and structured into several domains/motifs that are essential for ATF4 homo/heterodimerization, DNA binding, and the regulation of ATF4 at the protein stability level. The organization of the motifs modulating ATF4 protein stability is potentially essential for the regulation of ATF4 stability in response to stress, including hypoxic and anoxic insult. ATF4 has an oxygen dependent degradation domain (ODDD) motif which is recognized by the orthologs of C. elegans Egl-9, designated as PH (prolyl hydroxylase) domain containing enzymes (PHD) [also called HIF Prolyl Hydroxylase, HPH], specifically PHD3. The betaTrCP recognition motif is another degradation motif, which when phosphorylated, is recognized by betaTrCP and targeted for proteasomal degradation.
Expression ATF4 mRNA is transcribed ubiquitously, but protein expression and level is increased in cells that are exposed to various stress factors such as hypoxia, anoxia, lack of nutrition, as well as during development.
Localisation ATF4 protein is targeted to the nucleus. Single point mutations of basic amino acids within the basic region of ATF4 identified the sequence KKLKK (amino acids 280 to 284) as important for nuclear targeting.
Function ATF4 protein can function as a transcriptional activator, as well as a repressor. It is also a protective gene regulating the adaptation of cells to stress factors such as anoxic insult, endoplasmic reticulum stress and oxidative stress. ATF4 plays an essential role in development, and is particularly required for proper skeletal and eye development as well as haematopoiesis. ATF4 is also involved in proper function of memory. Furthermore, ATF4 is also a major factor in nutrition sensing, and has also been recently implicated in extreme hypoxia/anoxia mediated metastasis.
Metabolism: ATF4 is a conserved regulator of metabolism and carbohydrate homeostasis, and provides a mechanistic link between nutrients, insulin resistance, and diabetes, and has been described as a major mediator of nutrition-sensing response pathway, regulating the expression of asparagine synthetase (ASNS). In addition to regulating the expression of ASNS during lack of nutrition, ATF4 also regulates several aspects of mammalian metabolism, such as fat storage, energy expenditure, and glycemic control. The TOR pathway regulates invertebrate and vertebrate metabolism, and ATF4 mutant mice have reduced TOR signaling, and consequently reduced expression of genes important in the intracellular concentration of amino acids. Therefore, lack of ATF4 results in reduced concentration of amino acids, attributed to reduced TOR input. Thus, there is a close relationship between ATF4 function, the TOR pathway, and metabolism. This function of ATF4 also explains why type I collagen synthesis is specifically reduced in primary osteoblast cultures lacking ATF4, which can be rescued by adding nonessential amino acids to the culture. Thus, ATF4 is required for efficient amino acid import into osteoblasts.
Bone Metabolism: ATF4 is being considered as a global regulator of osteoblast biology and bone metabolism and formation. ATF4 supports bone formation through two mechanisms, which depend on its phosphorylation by RSK2. ATF4 regulates osteoblast-specific gene transcription and the synthesis of type I collagen, the main component of the bone extracellular matrix (ECM). ATF4 does this by favoring amino acid import, and therefore is a critical determinant of the synthesis of proteins in osteoblasts. Type I collagen is the most abundant protein of the bone ECM, and therefore, ATF4 is a major regulator of bone formation and of bone ECM mineralization. Consequently, ATF4-deficient mice are runted and harbor low bone mass, reduced osteoblast activity, decreased type I collagen synthesis, and inhibited osteocalcin and bone sialoprotein gene transcription.
Skeletogenesis: ATF4 plays an important role in assuring that osteoblasts fulfill their function. Rsk2-deficient mice display decreased bone mass due to impaired bone formation. ATF4 is more strongly phosphorylated by Rsk2 than any other proposed substrate. ATF4-deficient mice have revealed that this transcription factor plays several crucial roles in osteoblast differentiation and function. ATF4-deficient mice display a delayed skeletal development and result in a severe low-bone-mass phenotype caused by decreased bone formation.
Osteoclast differentiation: ATF4 regulates osteoclast differentiation and ultimately bone resorption through its expression in osteoblasts. ATF4 binds to the promoter of the receptor activator of nuclear factor-KappaB ligand (RankL) gene, which encodes a factor secreted by osteoblasts that promotes osteoclast differentiation. Accordingly, ATF4-deficient mice have decreased osteoclast numbers owing to reduced RankL expression.
Fetal liver hematopoiesis: A knockout mutation of ATF4 has demonstrated severe fetal anemia in mice. ATF4-/- Fetal livers are pale and hypoplastic, and the number of hematopoietic progenitors of multiple lineages is decreased more than 2 fold. Therefore, ATF4 is essential for the normal, high-level proliferation required for fetal-liver hematopoiesis.
Memory: ATF4 is a memory repressor that blocks the new expression of genes needed for memories, which appears to be a conserved mechanism. Decreasing the activity of ATF4 in mice or ApCREB2 (the ortholog of ATF4) in the sea slug Aplysia lowers the threshold for long-lasting changes and memory.
Homology Drosophila: Cryptocephal (CRC) gene.
C. elegans: According to WormBase, the C. elegans homologue of the human ATF4 gene is atf-5 (T04C10.4). The binding site of C. elegans ATF-5 is uncharacterized.

Mutations

Note A frameshift mutation is present in one allele of the ATF4 gene in F9 embryonal carcinoma stem cells. The mutation gives rise to the fusion of a short 5' open reading frame to the coding sequence of ATF4. Overexpression of mutant ATF4 suppresses ras-induced transformation.

Implicated in

Note
Note Implication of ATF4 in disease comes mainly from transgenic and in vitro studies. Studies in transgenic animals have indicated that ATF4 is required for skeletal and eye development, cellular proliferation, hematopoiesis, and neurological disorders, including memory. ATF4 has also been observed in greater levels in tumors than in normal tissue, suggesting that ATF4 signaling in hypoxic and anoxic areas of tumors might regulate processes relevant to cancer progression.
  
  
Entity Various cancers
Note ATF4 is a major factor induced by tumor hypoxia and anoxia, as well as lack of nutrition including low glucose levels. The expression of ATF4 has been noted to be greater in patient cancer compared to paired normal tissue. ATF4 is important for cellular survival under conditions of extreme hypoxia, including anoxia. Recently it has been shown that antiangiogenic treatment with avastin results in induction of ATF4 in vivo.
ATF4 renders cells resistant to multiple anti-cancer drugs and it has been implicated to be a multidrug resistant gene in cancer, and is involved in metastasis, by regulating the expression of the metastasis associated gene LAMP3.
Oncogenesis ATF4 is a major factor in regulating the expression of asparagine synthetase (ASNS) during hypoxia and nutritional deprivation (lack of amino acids and glucose). ASNS is associated with drug resistance in leukemia and oncogenesis triggered by mutated p53.
  
  
Entity Skeletal abnormalities of neurofibromatosis
Note There has been a link between increased Rsk2-dependent phosphorylation of ATF4 and the development of the skeletal abnormalities in human patients suffering from neurofibromatosis. This disease of tumor development in the nervous system, is caused by inactivating mutations of the neurofibromatosis 1 (NF 1), which plays a major physiological role in bone remodeling. The Nf1ob-/- (NF knockout specifically in osteoblasts) mice display a high bone mass phenotype. NF1 induces an increased production of type I collagen, attributed to Rsk2-dependent activation of ATF4. Thus, transgenic mice overexpressing ATF4 in osteoblasts display a phenotype similar to the Nf1ob-/- mice.
  
  
Entity Alzheimer's
Note In human brains, ATF4 and phospho-eIF2alpha levels are tightly correlated and up-regulated in Alzheimer disease, most probably representing an adaptive response against disease-related cellular stress rather than a correlate of neurodegeneration.
  
  
Entity Coffin-lowry syndrome
Note Coffin-Lowry Syndrome (CLS) is an X-linked mental retardation condition associated with skeletal abnormalities. ATF4 has been identified as a critical regulator of osteoblast differentiation and function, and lack of ATF4 phosphorylation by RSK2 may contribute to the skeletal phenotype of CLS.
  
  
Entity Vascular disease
Note ATF4 can be induced by both vascular injury and fibroblast growth factor-2 (FGF-2) and can serves as a conduit for the inducible expression of one growth factor by another during the process of intimal thickening.
  
  
Entity Joubert syndrome
Note The centrosomal protein, nephrocystin-6 (NPHP6), is disrupted in Joubert syndrome. NPHP6 interacts physically with and activates ATF4 as a signaling component on the level of transcriptional regulation in this disease group.
  
  
Entity Microphthalmia
Note Lack of ATF4 results in severe microphthalmia due to complete aphakia (absence of the eye lens). The affects of lack of ATF4 is attributed to p53 mediated apoptosis of anterior lens epithelial cells.
  

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Citation

This paper should be referenced as such :
Ameri, K ; Harris, AL
ATF4 (activating transcription factor 4 (tax-responsive enhancer element B67))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):739-743.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ATF4ID44413ch22q13.html


External links

Nomenclature
HGNC (Hugo)ATF4   786
Cards
AtlasATF4ID44413ch22q13
Entrez_Gene (NCBI)ATF4  468  activating transcription factor 4
AliasesCREB-2; CREB2; TAXREB67; TXREB
GeneCards (Weizmann)ATF4
Ensembl hg19 (Hinxton)ENSG00000128272 [Gene_View]  chr22:39916564-39918691 [Contig_View]  ATF4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000128272 [Gene_View]  chr22:39916564-39918691 [Contig_View]  ATF4 [Vega]
ICGC DataPortalENSG00000128272
TCGA cBioPortalATF4
AceView (NCBI)ATF4
Genatlas (Paris)ATF4
WikiGenes468
SOURCE (Princeton)ATF4
Genetics Home Reference (NIH)ATF4
Genomic and cartography
GoldenPath hg19 (UCSC)ATF4  -     chr22:39916564-39918691 +  22q13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ATF4  -     22q13.1   [Description]    (hg38-Dec_2013)
EnsemblATF4 - 22q13.1 [CytoView hg19]  ATF4 - 22q13.1 [CytoView hg38]
Mapping of homologs : NCBIATF4 [Mapview hg19]  ATF4 [Mapview hg38]
OMIM604064   
Gene and transcription
Genbank (Entrez)AK057751 AK296028 BC008090 BC011994 BC016855
RefSeq transcript (Entrez)NM_001675 NM_182810
RefSeq genomic (Entrez)NC_000022 NC_018933 NT_011520 NW_004929430
Consensus coding sequences : CCDS (NCBI)ATF4
Cluster EST : UnigeneHs.496487 [ NCBI ]
CGAP (NCI)Hs.496487
Alternative Splicing GalleryENSG00000128272
Gene ExpressionATF4 [ NCBI-GEO ]   ATF4 [ EBI - ARRAY_EXPRESS ]   ATF4 [ SEEK ]   ATF4 [ MEM ]
Gene Expression Viewer (FireBrowse)ATF4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)468
GTEX Portal (Tissue expression)ATF4
Protein : pattern, domain, 3D structure
UniProt/SwissProtP18848   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP18848  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP18848
Splice isoforms : SwissVarP18848
PhosPhoSitePlusP18848
Domaine pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domains : Interpro (EBI)ATF4    bZIP   
Domain families : Pfam (Sanger)bZIP_1 (PF00170)   
Domain families : Pfam (NCBI)pfam00170   
Domain families : Smart (EMBL)BRLZ (SM00338)  
Conserved Domain (NCBI)ATF4
DMDM Disease mutations468
Blocks (Seattle)ATF4
PDB (SRS)1CI6   
PDB (PDBSum)1CI6   
PDB (IMB)1CI6   
PDB (RSDB)1CI6   
Structural Biology KnowledgeBase1CI6   
SCOP (Structural Classification of Proteins)1CI6   
CATH (Classification of proteins structures)1CI6   
SuperfamilyP18848
Human Protein AtlasENSG00000128272
Peptide AtlasP18848
HPRD06817
IPIIPI00002503   
Protein Interaction databases
DIP (DOE-UCLA)P18848
IntAct (EBI)P18848
FunCoupENSG00000128272
BioGRIDATF4
STRING (EMBL)ATF4
ZODIACATF4
Ontologies - Pathways
QuickGOP18848
Ontology : AmiGORNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  core promoter sequence-specific DNA binding  transcription factor activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  microtubule organizing center  gluconeogenesis  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  cellular amino acid metabolic process  gamma-aminobutyric acid signaling pathway  protein C-terminus binding  positive regulation of vascular endothelial growth factor production  positive regulation of gene expression  negative regulation of translational initiation in response to stress  dendrite membrane  circadian regulation of gene expression  cellular response to amino acid starvation  nuclear periphery  cellular response to UV  response to endoplasmic reticulum stress  response to endoplasmic reticulum stress  positive regulation of transcription from RNA polymerase II promoter in response to stress  positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress  positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress  PERK-mediated unfolded protein response  cellular response to glucose starvation  mRNA transcription from RNA polymerase II promoter  neuron projection  positive regulation of apoptotic process  negative regulation of potassium ion transport  leucine zipper domain binding  positive regulation of neuron apoptotic process  sequence-specific DNA binding  transcription regulatory region DNA binding  transcription regulatory region DNA binding  transcription regulatory region DNA binding  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase I promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  negative regulation of oxidative stress-induced neuron death  Lewy body core  positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress  positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress  ATF4-CREB1 transcription factor complex  ATF1-ATF4 transcription factor complex  CHOP-ATF4 complex  CHOP-ATF4 complex  CHOP-ATF4 complex  response to manganese-induced endoplasmic reticulum stress  
Ontology : EGO-EBIRNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  core promoter sequence-specific DNA binding  transcription factor activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  microtubule organizing center  gluconeogenesis  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  cellular amino acid metabolic process  gamma-aminobutyric acid signaling pathway  protein C-terminus binding  positive regulation of vascular endothelial growth factor production  positive regulation of gene expression  negative regulation of translational initiation in response to stress  dendrite membrane  circadian regulation of gene expression  cellular response to amino acid starvation  nuclear periphery  cellular response to UV  response to endoplasmic reticulum stress  response to endoplasmic reticulum stress  positive regulation of transcription from RNA polymerase II promoter in response to stress  positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress  positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress  PERK-mediated unfolded protein response  cellular response to glucose starvation  mRNA transcription from RNA polymerase II promoter  neuron projection  positive regulation of apoptotic process  negative regulation of potassium ion transport  leucine zipper domain binding  positive regulation of neuron apoptotic process  sequence-specific DNA binding  transcription regulatory region DNA binding  transcription regulatory region DNA binding  transcription regulatory region DNA binding  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase I promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  negative regulation of oxidative stress-induced neuron death  Lewy body core  positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress  positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress  ATF4-CREB1 transcription factor complex  ATF1-ATF4 transcription factor complex  CHOP-ATF4 complex  CHOP-ATF4 complex  CHOP-ATF4 complex  response to manganese-induced endoplasmic reticulum stress  
Pathways : KEGGMAPK signaling pathway    Protein processing in endoplasmic reticulum    PI3K-Akt signaling pathway    Adrenergic signaling in cardiomyocytes    TNF signaling pathway    Long-term potentiation    Neurotrophin signaling pathway    Cholinergic synapse    Dopaminergic synapse    Insulin secretion    GnRH signaling pathway    Estrogen signaling pathway    Thyroid hormone synthesis    Non-alcoholic fatty liver disease (NAFLD)    Cocaine addiction    Amphetamine addiction    Alcoholism    Hepatitis B    HTLV-I infection    Viral carcinogenesis    Prostate cancer   
REACTOMEP18848 [protein]
REACTOME Pathways380994 [pathway]   381042 [pathway]   381183 [pathway]   
NDEx NetworkATF4
Atlas of Cancer Signalling NetworkATF4
Wikipedia pathwaysATF4
Orthology - Evolution
OrthoDB468
GeneTree (enSembl)ENSG00000128272
Phylogenetic Trees/Animal Genes : TreeFamATF4
HOVERGENP18848
HOGENOMP18848
Homologs : HomoloGeneATF4
Homology/Alignments : Family Browser (UCSC)ATF4
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerATF4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ATF4
dbVarATF4
ClinVarATF4
1000_GenomesATF4 
Exome Variant ServerATF4
ExAC (Exome Aggregation Consortium)ATF4 (select the gene name)
Genetic variants : HAPMAP468
Genomic Variants (DGV)ATF4 [DGVbeta]
DECIPHER (Syndromes)22:39916564-39918691  ENSG00000128272
CONAN: Copy Number AnalysisATF4 
Mutations
ICGC Data PortalATF4 
TCGA Data PortalATF4 
Broad Tumor PortalATF4
OASIS PortalATF4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICATF4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDATF4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ATF4
DgiDB (Drug Gene Interaction Database)ATF4
DoCM (Curated mutations)ATF4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ATF4 (select a term)
intoGenATF4
NCG5 (London)ATF4
Cancer3DATF4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604064   
Orphanet
MedgenATF4
Genetic Testing Registry ATF4
NextProtP18848 [Medical]
TSGene468
GENETestsATF4
Huge Navigator ATF4 [HugePedia]
snp3D : Map Gene to Disease468
BioCentury BCIQATF4
ClinGenATF4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD468
Chemical/Pharm GKB GenePA25086
Clinical trialATF4
Miscellaneous
canSAR (ICR)ATF4 (select the gene name)
Probes
Litterature
PubMed192 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineATF4
EVEXATF4
GoPubMedATF4
iHOPATF4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:28:03 CEST 2017

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