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 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr22:39,520,564-39,522,683)mRNA (may differ from genome)Protein (351 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
HGNCHPRDLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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.

-  MalaCards Disease Associations
  MalaCards Gene Search: ATF4
Diseases sorted by gene-association score: autosomal recessive nonsyndromic deafness 47 (11), coffin-lowry syndrome (10), leukoencephalopathy with vanishing white matter (9), t-cell leukemia (5), fatty liver disease (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 355.50 RPKM in Colon - Sigmoid
Total median expression: 7959.60 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -404.50882-0.459 Picture PostScript Text
3' UTR -16.3081-0.201 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004827 - bZIP

Pfam Domains:
PF00170 - bZIP transcription factor

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1CI6
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P18848
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005815 microtubule organizing center
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0032590 dendrite membrane
GO:0032991 macromolecular complex
GO:0034399 nuclear periphery
GO:0043005 neuron projection
GO:1990037 Lewy body core
GO:1990589 ATF4-CREB1 transcription factor complex
GO:1990590 ATF1-ATF4 transcription factor complex
GO:1990617 CHOP-ATF4 complex
GO:0005813 centrosome


-  Descriptions from all associated GenBank mRNAs
  AK296028 - Homo sapiens cDNA FLJ58799 complete cds, highly similar to Cyclic AMP-dependent transcription factor ATF-4.
AK057751 - Homo sapiens cDNA FLJ25022 fis, clone CBL01850, highly similar to CYCLIC-AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-4.
D90209 - Homo sapiens mRNA for DNA binding protein TAXREB67, complete cds.
BC008090 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:9337 IMAGE:3454473), complete cds.
BC022088 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:4076 IMAGE:3030097), complete cds.
BC011994 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:10001 IMAGE:3882614), complete cds.
BC024775 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:30184 IMAGE:4992862), complete cds.
BC016855 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:17066 IMAGE:3850361), complete cds.
BC073754 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:88758 IMAGE:6580199), complete cds.
BC044895 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:25133 IMAGE:4513828), complete cds.
BC073990 - Homo sapiens activating transcription factor 4 (tax-responsive enhancer element B67), mRNA (cDNA clone MGC:88042 IMAGE:6022488), complete cds.
JD106443 - Sequence 87467 from Patent EP1572962.
JD493720 - Sequence 474744 from Patent EP1572962.
JD217692 - Sequence 198716 from Patent EP1572962.
JD348513 - Sequence 329537 from Patent EP1572962.
CR456384 - Homo sapiens ATF4 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.ATF4.V4).
JD528880 - Sequence 509904 from Patent EP1572962.
JD258165 - Sequence 239189 from Patent EP1572962.
M86842 - Human cAMP response element regulatory protein (CREB2) mRNA, complete cds.
CU013230 - Homo sapiens ATF4, mRNA (cDNA clone IMAGE:100000010), complete cds, without stop codon, in Gateway system.
CU012942 - Homo sapiens ATF4, mRNA (cDNA clone IMAGE:100000106), complete cds, with stop codon, in Gateway system.
CU680154 - Synthetic construct Homo sapiens gateway clone IMAGE:100017071 5' read ATF4 mRNA.
AB489145 - Synthetic construct DNA, clone: pF1KB9540, Homo sapiens ATF4 gene for activating transcription factor 4, without stop codon, in Flexi system.
DQ894942 - Synthetic construct Homo sapiens clone IMAGE:100009402; FLH179657.01L; RZPDo839B01131D activating transcription factor 4 (tax-responsive enhancer element B67) (ATF4) gene, encodes complete protein.
KJ905692 - Synthetic construct Homo sapiens clone ccsbBroadEn_15362 ATF4 gene, encodes complete protein.
KJ890723 - Synthetic construct Homo sapiens clone ccsbBroadEn_00117 ATF4 gene, encodes complete protein.
DQ891758 - Synthetic construct clone IMAGE:100004388; FLH179661.01X; RZPDo839B01132D activating transcription factor 4 (tax-responsive enhancer element B67) (ATF4) gene, encodes complete protein.
CR450353 - Homo sapiens full open reading frame cDNA clone RZPDo834H102D for gene ATF4, activating transcription factor 4 (tax-responsive enhancer element B67); complete cds; without stopcodon.
DQ589665 - Homo sapiens piRNA piR-56777, complete sequence.
JD024990 - Sequence 6014 from Patent EP1572962.
JD029929 - Sequence 10953 from Patent EP1572962.
DQ601415 - Homo sapiens piRNA piR-39481, complete sequence.
JD023996 - Sequence 5020 from Patent EP1572962.
JD032567 - Sequence 13591 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04720 - Long-term potentiation
hsa04722 - Neurotrophin signaling pathway
hsa04912 - GnRH signaling pathway
hsa05215 - Prostate cancer

Reactome (by CSHL, EBI, and GO)

Protein P18848 (Reactome details) participates in the following event(s):

R-HSA-381042 PERK regulates gene expression
R-HSA-381119 Unfolded Protein Response (UPR)
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: ATF4_HUMAN, CREB2, NM_001675, P18848, Q9UH31, TXREB, uc003aya.1, uc003aya.2, uc003aya.3, uc003aya.4
UCSC ID: uc003aya.4
RefSeq Accession: NM_001675
Protein: P18848 (aka ATF4_HUMAN)
CCDS: CCDS13996.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.