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Aliases for ATF4 Gene

Aliases for ATF4 Gene

  • Activating Transcription Factor 4 2 3 4
  • TAXREB67 3 4 6
  • CREB2 3 4 6
  • Tax-Responsive Enhancer Element-Binding Protein 67 3 4
  • Cyclic AMP-Responsive Element-Binding Protein 2 3 4
  • CAMP-Responsive Element-Binding Protein 2 3 4
  • CAMP-Dependent Transcription Factor ATF-4 3 4
  • Tax-Responsive Enhancer Element B67 2 3
  • DNA-Binding Protein TAXREB67 3 4
  • CREB-2 3 4
  • TXREB 3 4
  • Activating Transcription Factor 4 (Tax-Responsive Enhancer Element B67) 2
  • Cyclic AMP-Dependent Transcription Factor ATF-4 3
  • CAMP Response Element-Binding Protein 2 3

External Ids for ATF4 Gene

Previous HGNC Symbols for ATF4 Gene

  • TXREB

Previous GeneCards Identifiers for ATF4 Gene

  • GC22P036531
  • GC22P038158
  • GC22P038159
  • GC22P038241
  • GC22P039916
  • GC22P022881

Summaries for ATF4 Gene

Entrez Gene Summary 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. Among its related pathways are PI3K-Akt signaling pathway and MAPK signaling pathway. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and protein C-terminus binding. An important paralog of this gene is ATF5.

UniProtKB/Swiss-Prot for ATF4 Gene

  • 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. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. 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.

Gene Wiki entry for ATF4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ATF4 Gene

Genomics for ATF4 Gene

Regulatory Elements for ATF4 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for ATF4 Gene

Start:
39,519,695 bp from pter
End:
39,522,686 bp from pter
Size:
2,992 bases
Orientation:
Plus strand

Genomic View for ATF4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ATF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ATF4 Gene

Proteins for ATF4 Gene

  • Protein details for ATF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P18848-ATF4_HUMAN
    Recommended name:
    Cyclic AMP-dependent transcription factor ATF-4
    Protein Accession:
    P18848
    Secondary Accessions:
    • Q9UH31

    Protein attributes for ATF4 Gene

    Size:
    351 amino acids
    Molecular mass:
    38590 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for ATF4 Gene

neXtProt entry for ATF4 Gene

Proteomics data for ATF4 Gene at MOPED

Post-translational modifications for ATF4 Gene

  • Phosphorylated by NEK6 (By similarity). Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination. Phosphorylation is promoted by mTORC1 (By similarity).
  • Phosphorylated by NEK6.
  • Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4.
  • Ubiquitination at Lys329
  • Modification sites at PhosphoSitePlus

Other Protein References for ATF4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for ATF4 (ATF-4)

No data available for DME Specific Peptides for ATF4 Gene

Domains for ATF4 Gene

Gene Families for ATF4 Gene

HGNC:
  • bZIP :basic leucine zipper proteins

Protein Domains for ATF4 Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

P18848

UniProtKB/Swiss-Prot:

ATF4_HUMAN :
  • P18848
Domain:
  • The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.
  • Contains 1 bZIP (basic-leucine zipper) domain.
Family:
  • Belongs to the bZIP family.
genes like me logo Genes that share domains with ATF4: view

Function for ATF4 Gene

Molecular function for ATF4 Gene

GENATLAS Biochemistry: activation transcription factor 4,cAMP dependent,for a tax responsive enhancer element B67 in the long terminal repeat of human T cell leukemia virus type I
UniProtKB/Swiss-Prot 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. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. 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.

Gene Ontology (GO) - Molecular Function for ATF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IEA --
GO:0000981 sequence-specific DNA binding RNA polymerase II transcription factor activity IDA 11478948
GO:0001046 core promoter sequence-specific DNA binding ISS --
GO:0001076 RNA polymerase II transcription factor binding transcription factor activity IC 12871976
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IEA --
genes like me logo Genes that share ontologies with ATF4: view
genes like me logo Genes that share phenotypes with ATF4: view

Animal Models for ATF4 Gene

MGI Knock Outs for ATF4:

Animal Model Products

CRISPR Products

miRNA for ATF4 Gene

Targeting motifs for ATF4 Gene
HOMER Transcription Factor Regulatory Elements motif ATF4
  • Consensus sequence: MTGATGCAAT Submotif: canonical Cell Type: MEF GeoId: GSE35681

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for ATF4

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targeting for ATF4 Gene

Localization for ATF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ATF4 Gene

Cytoplasm. Cell membrane. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Co- localizes with NEK6 in the centrosome. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ATF4 Gene COMPARTMENTS Subcellular localization image for ATF4 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
plasma membrane 5
cytosol 3
endoplasmic reticulum 3
mitochondrion 2
extracellular 1

Gene Ontology (GO) - Cellular Components for ATF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex --
GO:0005737 cytoplasm ISS --
GO:0005815 microtubule organizing center IEA --
genes like me logo Genes that share ontologies with ATF4: view

Pathways for ATF4 Gene

genes like me logo Genes that share pathways with ATF4: view

PCR Array Products

Gene Ontology (GO) - Biological Process for ATF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006094 gluconeogenesis ISS --
GO:0006355 regulation of transcription, DNA-templated ISS --
GO:0006357 regulation of transcription from RNA polymerase II promoter --
GO:0006366 transcription from RNA polymerase II promoter ISS --
GO:0006520 cellular amino acid metabolic process TAS 12689582
genes like me logo Genes that share ontologies with ATF4: view

Compounds for ATF4 Gene

(1) HMDB Compounds for ATF4 Gene

Compound Synonyms Cas Number PubMed IDs
Cyclic AMP
  • Cyclic AMP
60-92-4

(31) Novoseek inferred chemical compound relationships for ATF4 Gene

Compound -log(P) Hits PubMed IDs
tunicamycin 77.5 6
leucine 62.1 17
bortezomib 61.5 8
amino acid 59.6 10
thapsigargin 59.2 6
genes like me logo Genes that share compounds with ATF4: view

Transcripts for ATF4 Gene

Unigene Clusters for ATF4 Gene

Activating transcription factor 4 (tax-responsive enhancer element B67):
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for ATF4

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for ATF4 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3
SP1: -
SP2:

Relevant External Links for ATF4 Gene

GeneLoc Exon Structure for
ATF4
ECgene alternative splicing isoforms for
ATF4

Expression for ATF4 Gene

mRNA expression in normal human tissues for ATF4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for ATF4 Gene

SOURCE GeneReport for Unigene cluster for ATF4 Gene Hs.496487

genes like me logo Genes that share expressions with ATF4: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for ATF4 Gene

Orthologs for ATF4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ATF4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ATF4 35
  • 99.43 (n)
  • 99.15 (a)
ATF4 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ATF4 35
  • 88.05 (n)
  • 85.55 (a)
ATF4 36
  • 85 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ATF4 35
  • 90.45 (n)
  • 91.12 (a)
ATF4 36
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Atf4 35
  • 86.49 (n)
  • 87.07 (a)
Atf4 16
Atf4 36
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ATF4 36
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ATF4 36
  • 57 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Atf4 35
  • 86.46 (n)
  • 88.18 (a)
chicken
(Gallus gallus)
Aves ATF4 35
  • 68.4 (n)
  • 63.87 (a)
ATF4 36
  • 62 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ATF4 36
  • 60 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia MGC68539 35
tropical clawed frog
(Silurana tropicalis)
Amphibia atf4 35
  • 63.8 (n)
  • 61.15 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.832 35
zebrafish
(Danio rerio)
Actinopterygii atf4b1 36
  • 35 (a)
OneToMany
atf4b2 35
  • 49.2 (n)
  • 46.49 (a)
atf4b2 36
  • 27 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2035 36
  • 21 (a)
OneToMany
Species with no ortholog for ATF4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ATF4 Gene

ENSEMBL:
Gene Tree for ATF4 (if available)
TreeFam:
Gene Tree for ATF4 (if available)

Paralogs for ATF4 Gene

Paralogs for ATF4 Gene

Pseudogenes.org Pseudogenes for ATF4 Gene

genes like me logo Genes that share paralogs with ATF4: view

Variants for ATF4 Gene

Sequence variations from dbSNP and Humsavar for ATF4 Gene

SNP ID Clin Chr 22 pos Sequence Context AA Info Type MAF
rs4894 - 39,521,510(+) CGACC(A/C)GTCGG reference, missense
rs1060000 -- 39,522,587(+) GGGAA(A/G)AAAAG synonymous-codon, reference
rs1060142 -- 39,521,024(+) GCCCC(A/G)CGAAA utr-variant-5-prime, intron-variant
rs1803323 - 39,522,318(+) CCCGT(C/G)CCAAA reference, missense
rs1803324 - 39,522,512(+) AAAGA(C/G)AGGGC missense, reference

Structural Variations from Database of Genomic Variants (DGV) for ATF4 Gene

Variant ID Type Subtype PubMed ID
nsv834199 CNV Loss 17160897
nsv915099 CNV Loss 21882294
nsv3629 CNV Insertion 18451855

Relevant External Links for ATF4 Gene

HapMap Linkage Disequilibrium report
ATF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ATF4 Gene

Disorders for ATF4 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (1) Diseases for ATF4 Gene including...

Search for ATF4 Gene in MalaCards »

(7) Novoseek inferred disease relationships for ATF4 Gene

Disease -log(P) Hits PubMed IDs
leukemia t-cell 53.7 2
cancer 31.8 8
tumors 17.9 4
pancreatic cancer 9.09 1
ischemia 0 1

Relevant External Links for ATF4

Genetic Association Database (GAD)
ATF4
Human Genome Epidemiology (HuGE) Navigator
ATF4
genes like me logo Genes that share disorders with ATF4: view

No data available for UniProtKB/Swiss-Prot for ATF4 Gene

Publications for ATF4 Gene

  1. Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA. (PMID: 11018027) Podust L.M. … Kim Y. (J. Biol. Chem. 2001) 3 4 23
  2. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. (PMID: 15775988) Ohoka N. … Hayashi H. (EMBO J. 2005) 3 4 23
  3. Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. (PMID: 17346882) Kakiuchi C. … Kato T. (Neurosci. Lett. 2007) 3 23 48
  4. Associations of ATF4 gene polymorphisms with schizophrenia in male patients. (PMID: 18163433) Qu M. … Zhang D. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008) 3 23 48
  5. Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element. (PMID: 1534408) Karpinski B.A. … Leiden J.M. (Proc. Natl. Acad. Sci. U.S.A. 1992) 2 3 4

Products for ATF4 Gene

  • Addgene plasmids for ATF4

Sources for ATF4 Gene

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