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ATF4 Gene

protein-coding   GIFtS: 67
GCID: GC22P039916

Activating Transcription Factor 4

(Previous name: activating transcription factor 4 (tax-responsive enhancer...)
(Previous symbol: TXREB)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Activating Transcription Factor 41 2 3     CAMP-Responsive Element-Binding Protein 22 3
TXREB1 2 3     DNA-Binding Protein TAXREB672 3
CREB22 3 5     TAXREB672 5
Tax-Responsive Enhancer Element B671 2     Activating Transcription Factor 4 (Tax-Responsive Enhancer Element B67)1
Cyclic AMP-Responsive Element-Binding Protein 22 3     CAMP Response Element-Binding Protein 22
Tax-Responsive Enhancer Element-Binding Protein 672 3     Cyclic AMP-Dependent Transcription Factor ATF-42
CREB-22 3     TaxREB673
CAMP-Dependent Transcription Factor ATF-42 3     

External Ids:    HGNC: 7861   Entrez Gene: 4682   Ensembl: ENSG000001282727   OMIM: 6040645   UniProtKB: P188483   

Export aliases for ATF4 gene to outside databases

Previous GC identifers: GC22P036531 GC22P038158 GC22P038159 GC22P038241 GC22P022881


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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, and hepatitis e. GO annotations related to this gene include protein C-terminus binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is ATF5.

UniProtKB/Swiss-Prot: ATF4_HUMAN, P18848
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

Gene Wiki entry for ATF4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000022.11  NC_018933.2  NT_011520.13  
Regulatory elements:
   Regulatory transcription factor binding sites in the ATF4 gene promoter:
         CREB   C/EBPbeta   AP-1   ATF-2   deltaCREB   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidATF4 promoter sequence
   Search Chromatin IP Primers for ATF4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ATF4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q13.1   Ensembl cytogenetic band:  22q13.1   HGNC cytogenetic band: 22q13.1

ATF4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ATF4 gene location

GeneLoc information about chromosome 22         GeneLoc Exon Structure

GeneLoc location for GC22P039916:  view genomic region     (about GC identifiers)

Start:
39,915,700 bp from pter      End:
39,918,691 bp from pter
Size:
2,992 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: ATF4_HUMAN, P18848 (See protein sequence)
Recommended Name: Cyclic AMP-dependent transcription factor ATF-4  
Size: 351 amino acids; 38590 Da
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
1 PDB 3D structure from and Proteopedia for ATF4:
1CI6 (3D)    
Secondary accessions: Q9UH31

Explore the universe of human proteins at neXtProt for ATF4: NX_P18848

Explore proteomics data for ATF4 at MOPED

Post-translational modifications: 

  • Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to
    down-regulate expression of SIRT4 (By similarity)1
  • 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)1
  • Phosphorylated by NEK61
  • Ubiquitination2 at Lys329
  • Modification sites at PhosphoSitePlus

  • See ATF4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001666.2  NP_877962.1  

    ENSEMBL proteins: 
     ENSP00000384587   ENSP00000336790   ENSP00000379912  
    Reactome Protein details: P18848

    ATF4 Human Recombinant Protein Products:

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    Novus Biologicals ATF4 Proteins
    Novus Biologicals ATF4 Lysate
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    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for ATF4
    Cloud-Clone Corp. Proteins for ATF4

    ATF4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ATF4
    R&D Systems Antibodies for ATF4
    Cell Signaling Technology (CST) Antibodies for ATF4  (ATF-4)
    OriGene Antibodies for ATF4
    OriGene Custom Antibody Services for ATF4
    Novus Biologicals ATF4 Antibodies
    Abcam antibodies for ATF4 (Q96AQ3, P18848)
    Cloud-Clone Corp. Antibodies for ATF4
    ThermoFisher Antibodies for ATF4
    LSBio Antibodies in human, mouse, rat for ATF4

    ATF4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for ATF4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for ATF4
    Cloud-Clone Corp. CLIAs for ATF4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    bZIP: basic leucine zipper proteins

    1 InterPro protein domain:
     IPR004827 bZIP

    Graphical View of Domain Structure for InterPro Entry P18848

    ProtoNet protein and cluster: P18848

    1 Blocks protein domain: IPB011616 bZIP transcription factor

    UniProtKB/Swiss-Prot: ATF4_HUMAN, P18848
    Domain: The BetaTrCP degron motif promotes binding to BTRC when phosphorylated (By similarity)
    Similarity: Belongs to the bZIP family
    Similarity: Contains 1 bZIP (basic-leucine zipper) domain


    ATF4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ATF4_HUMAN, P18848
    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

         Genatlas biochemistry entry for ATF4:
    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

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding ISS--
    GO:0003700sequence-specific DNA binding transcription factor activity TAS12689582
    GO:0005515protein binding IPI11238952
    GO:0008022protein C-terminus binding IEA--
    GO:0043565sequence-specific DNA binding IEA--
         
    ATF4 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for ATF4:
     Increased cell death HMECs cel 

         15 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Atf4):
     adipose tissue  cellular  craniofacial  digestive/alimentary  endocrine/exocrine gland 
     growth/size/body  hematopoietic system  homeostasis/metabolism  integument  liver/biliary system 
     mortality/aging  muscle  reproductive system  skeleton  vision/eye 

    ATF4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for ATF4: Atf4tm1Tow Atf4tm1Jml Atf4tm1Aki

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ATF4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ATF4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ATF4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ATF4

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  MTGATGCAAT 

    miRNA
    Products:
        
    miRTarBase miRNAs that target ATF4:
    hsa-mir-214-3p (MIRT007201), hsa-mir-342-3p (MIRT043684), hsa-mir-196b-5p (MIRT042655)

    Block miRNA regulation of human, mouse, rat ATF4 using miScript Target Protectors
    2 qRT-PCR Assays for microRNAs that regulate ATF4:
    hsa-miR-1283 hsa-miR-32*
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for ATF4
    Predesigned siRNA for gene silencing in human, mouse, rat ATF4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ATF4

    Clone
    Products:
         
    OriGene clones in human, mouse for ATF4 (see all 14)
    OriGene ORF clones in mouse, rat for ATF4
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    GenScript: all cDNA clones in your preferred vector (see all 2): ATF4 (NM_001675)
    Sino Biological Human cDNA Clone for ATF4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ATF4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ATF4

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    Browse ESI BIO Cell Lines and PureStem Progenitors for ATF4 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ATF4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ATF4_HUMAN, P18848: 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    nucleus5
    plasma membrane5
    cytosol3
    endoplasmic reticulum3
    mitochondrion2
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ISS--
    GO:0005654nucleoplasm TAS--
    GO:0005667transcription factor complex IEA--
    GO:0005737cytoplasm ISS--
    GO:0005815microtubule organizing center IEA--

    ATF4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ATF4 About   (see all 55)  
    See pathways by source

    SuperPathContained pathways About
    1MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    2Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    Activation of PKA through GPCR0.71
    cAMP Pathway0.77
    PKA Signaling0.56
    3CREB Pathway
    CREB Pathway0.68
    Activation of PKC through GPCR0.63
    IP3 Pathway0.68
    Intracellular Calcium Signaling0.50
    4GPCR Pathway
    GPCR Pathway0.62
    P2Y Receptor Signaling0.38
    Estrogen Pathway0.55
    5Unfolded Protein Response
    Unfolded Protein Response0.61
    Activation of Chaperone Genes by ATF6-alpha0.00
    Activation of Chaperones by ATF6-alpha0.00

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for ATF4
        TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ATF4 (see all 53)
        FLT3 Signaling
    Nuclear Receptor Activation by Vitamin-A
    Toll-Like Receptors Pathway
    Interferon Pathway
    Intracellular Calcium Signaling

    1 Cell Signaling Technology (CST) Pathway for ATF4
        Glucose / Energy Metabolism

    2 BioSystems Pathways for ATF4
        Myometrial Relaxation and Contraction Pathways
    MAPK signaling pathway


    3 Reactome Pathways for ATF4
        PERK regulates gene expression
    ATF6-alpha activates chaperone genes
    ATF4 activates genes


    Selected Kegg Pathways  (Kegg details for ATF4) (see all 21):
        MAPK signaling pathway
    Protein processing in endoplasmic reticulum
    PI3K-Akt signaling pathway
    Adrenergic signaling in cardiomyocytes
    TNF signaling pathway


    ATF4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ATF4 (see all 9): 
              TGFB/BMP Signaling Pathway in human mouse rat
              Stress & Toxicity PathwayFinder in human mouse rat
              TGFB Signaling Targets in human mouse rat
              Neurotoxicity in human mouse rat
              Signal Transduction PathwayFinder in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ATF4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ATF4 (P188481, 2, 3 ENSP000003367904) via UniProtKB, MINT, STRING, and/or I2D (see all 113)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CREBZFQ9NS371, 2, 3, ENSP000002600584EBI-492498,EBI-632965 MINT-73538 MINT-73537 MINT-73540 MINT-73535 MINT-73539 I2D: score=2 STRING: ENSP00000260058
    POLR2CP193872, 3, ENSP000002192524MINT-49646 MINT-49647 MINT-49645 MINT-49644 MINT-49643 I2D: score=4 STRING: ENSP00000219252
    TRIB3Q96RU71, 3, ENSP000002172334EBI-492498,EBI-492476 I2D: score=6 STRING: ENSP00000217233
    DISC1Q9NRI51, 3, ENSP000003555964EBI-492498,EBI-529989 I2D: score=4 STRING: ENSP00000355596
    BTRCQ9Y2971, 3, ENSP000003592064EBI-492498,EBI-307461 I2D: score=2 STRING: ENSP00000359206
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006094gluconeogenesis ISS--
    GO:0006355regulation of transcription, DNA-templated ISS--
    GO:0006357regulation of transcription from RNA polymerase II promoter ----
    GO:0006366transcription from RNA polymerase II promoter ISS--
    GO:0006520cellular amino acid metabolic process TAS12689582

    ATF4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ATF4

    1 HMDB Compound for ATF4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Cyclic AMPCyclic AMP (see all 19)60-92-4--

    Selected Novoseek inferred chemical compound relationships for ATF4 gene (see all 31)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tunicamycin 77.5 7 15775988 (2), 19100962 (1), 16931790 (1), 17941056 (1) (see all 5)
    leucine 62.1 19 15677469 (3), 11018027 (2), 15663480 (1), 20392257 (1) (see all 14)
    bortezomib 61.5 12 19417138 (4), 20022965 (2), 16846475 (1), 18341633 (1)
    amino acid 59.6 14 14630918 (5), 16026328 (2), 16989641 (1), 17276738 (1) (see all 5)
    thapsigargin 59.2 7 19100962 (1), 20022965 (1), 15781252 (1), 19561125 (1) (see all 6)
    cyclic amp 46.6 9 15663480 (1), 18957537 (1), 17466566 (1), 16343488 (1) (see all 6)
    asparagine 45.6 1 17369260 (1)
    noxa 41.1 4 20022965 (1), 19164757 (1), 20085765 (1)
    celecoxib 38.6 12 17167033 (2), 16205636 (2), 19073601 (1)
    palmitate 30.8 8 17395747 (1), 16601139 (1), 18492819 (1), 17268797 (1)



    ATF4 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for ATF4 gene (2 alternative transcripts): 
    NM_001675.4  NM_182810.2  

    Unigene Cluster for ATF4:

    Activating transcription factor 4 (tax-responsive enhancer element B67)
    Hs.496487  [show with all ESTs]
    Unigene Representative Sequence: NM_001675
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000404241 ENST00000337304(uc003aya.3) ENST00000396680(uc011aol.1 uc003axz.3)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    2 qRT-PCR Assays for microRNAs that regulate ATF4:
    hsa-miR-1283 hsa-miR-32*
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 2): ATF4 (NM_001675)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ATF4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ATF4
    Primer
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    OriGene qPCR primer pairs and template standards for ATF4
    OriGene qSTAR qPCR primer pairs in human, mouse for ATF4
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat ATF4
      QuantiTect SYBR Green Assays in human, mouse, rat ATF4
      QuantiFast Probe-based Assays in human, mouse, rat ATF4

    Additional mRNA sequence: 

    AK057751.1 AK296028.1 BC008090.1 BC011994.1 BC016855.2 BC022088.2 BC024775.1 BC044895.1 
    BC073754.1 BC073990.1 CR450353.1 CR456384.1 D90209.1 M86842.1 

    Selected DOTS entries (see all 55):

    DT.91998220  DT.100045356  DT.95344549  DT.100706342  DT.95344559  DT.91699853  DT.100846900  DT.91842913 
    DT.100866528  DT.120639148  DT.100803506  DT.92000118  DT.91974463  DT.87017151  DT.95219578  DT.120639306 
    DT.120639096  DT.95344651  DT.100706351  DT.102839308  DT.91795184  DT.91999377  DT.95103057  DT.100855961 

    Selected AceView cDNA sequences (see all 2626):

    BI062411 BM552932 BQ066841 BU738254 BC002587 CB157745 BU857697 BQ000048 
    CR595416 CR605980 BM745128 BE281414 AA320077 BE784055 AV701556 BI870016 
    CA442297 BC002861 BX384576 AA340952 BF724703 BQ926577 AU129380 AI124836 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for ATF4    About this scheme

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


    ECgene alternative splicing isoforms for ATF4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ATF4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATCCCTCAGT
    ATF4 Expression
    About this image


    ATF4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 21) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 10 entries
             Intramembranous Osteoblasts Membranous Facial Bones
             Bone Marrow
     
     Neural Tube (Nervous System)
             Rhombencephalon
     
     Brain (Nervous System)
             Cerebral Cortex
     
     Limb (Muscoskeletal System)
             Limb Bud
     
     Colon (Gastrointestinal Tract)
    ATF4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ATF4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.496487
        Pathway & Disease-focused RT2 Profiler PCR Arrays including ATF4 (see all 9): 
              TGFB/BMP Signaling Pathway in human mouse rat
              Stress & Toxicity PathwayFinder in human mouse rat
              TGFB Signaling Targets in human mouse rat
              Neurotoxicity in human mouse rat
              Signal Transduction PathwayFinder in human mouse rat

    Primer
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for ATF4 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Atf41 , 5 activating transcription factor 41, 5 86.49(n)1
    87.07(a)1
      15 (37.85 cM)5
    119111  NM_001287180.11  NP_001274109.11 
     802551845 
    chicken
    (Gallus gallus)
    Aves ATF41 activating transcription factor 4 (tax-responsive enhancer more 68.4(n)
    63.87(a)
      395693  NM_204880.2  NP_990211.1 
    lizard
    (Anolis carolinensis)
    Reptilia ATF46
    activating transcription factor 4
    60(a)
    1 ↔ 1
    5(24911810-24913115)
    African clawed frog
    (Xenopus laevis)
    Amphibia MGC685392 hypothetical protein MGC68539 76.24(n)    BC059971.1 
    zebrafish
    (Danio rerio)
    Actinopterygii atf4b21 activating transcription factor 4b2 49.2(n)
    46.49(a)
      556410  NM_001103192.1  NP_001096662.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ATF4 gene
    ATF52  

    ATF4 for paralogs           About GeneDecksing


    3 Pseudogenes.org Pseudogenes for ATF4
    PGOHUM00000242898 PGOHUM00000241613 PGOHUM00000242094


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ATF4 (see all 182)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 22 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1123037311,2
    F--39914646(+) ACTTCC/TGTATA 2 -- us2k11Minor allele frequency- T:0.50CSA 2
    rs1406988801,2
    --39914649(+) TCTGTA/GTATCT 2 -- us2k10--------
    rs2009552391,2
    C--39914738(+) TTAAA-/GTTGTTGG 2 -- us2k10--------
    rs360598721,2
    C,F--39914792(+) CAGGAC/GGATGT 2 -- us2k10--------
    rs1882949821,2
    --39915127(+) CCATTA/GGGCCT 2 -- us2k10--------
    rs1139109981,2
    F--39915213(+) GCTTCG/CCTGGT 2 -- us2k11Minor allele frequency- C:0.50CSA 2
    rs1119378891,2
    F--39915229(+) GATATC/AACAGC 2 -- us2k11Minor allele frequency- A:0.50CSA 2
    rs787423691,2
    F--39915258(+) CAGTGA/TAATGG 2 -- us2k11Minor allele frequency- T:0.04WA 118
    rs1427628101,2
    --39915419(+) CCTGGA/GCCATG 2 -- us2k10--------
    rs594781411,2
    C--39915826(+) GCAGG-/GCCACA 2 -- us2k10--------

    HapMap Linkage Disequilibrium report for ATF4 (39915700 - 39918691 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for ATF4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv3629CNV Insertion18451855
    nsv915099CNV Loss21882294
    nsv834199CNV Loss17160897

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing ATF4
    DNA2.0 Custom Variant and Variant Library Synthesis for ATF4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604064    OMIM disorders: --

    Selected diseases for ATF4 (see all 39):    
    About MalaCards
    coffin-lowry syndrome    hepatitis e    anoxia    joubert syndrome
    idiopathic pulmonary fibrosis    human t-cell leukemia virus type 1    pulmonary fibrosis    hypoglycemia
    t-cell leukemia    hypoxia    thyroid cancer    fatty liver disease
    ischemia    bipolar disorder    pancreatic cancer    periodontitis
    hepatitis    pancreatitis    hepatitis c virus    schizophrenia


    ATF4 for disorders           About GeneDecksing

    7 Novoseek inferred disease relationships for ATF4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    leukemia t-cell 53.7 2 12202230 (1), 16458341 (1)
    cancer 31.8 11 17297441 (2), 17466566 (2), 10667576 (1), 14604972 (1) (see all 6)
    tumors 17.9 18 19519398 (2), 16148948 (1), 18829529 (1)
    pancreatic cancer 9.09 1 17409444 (1)
    ischemia 0 1 18082969 (1)
    shock 0 2 15081838 (1), 16846475 (1)
    breast cancer 0 3 19417138 (2)

    Genetic Association Database (GAD): ATF4
    Human Genome Epidemiology (HuGE) Navigator: ATF4 (6 documents)

    Export disorders for ATF4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ATF4 gene, integrated from 10 sources (see all 310):
    (articles sorted by number of sources associating them with ATF4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element. (PubMed id 1534408)1, 2, 3 Karpinski B.A.... Leiden J.M. (Proc. Natl. Acad. Sci. U.S.A. 1992)
    2. Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I. (PubMed id 1847461)1, 2, 3 Tsujimoto A.... Shimotohno K. (J. Virol. 1991)
    3. Associations of ATF4 gene polymorphisms with schizophrenia in male patients. (PubMed id 18163433)1, 4, 9 Qu M....Zhang D. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008)
    4. Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. (PubMed id 17346882)1, 4, 9 Kakiuchi C....Kato T. (Neurosci. Lett. 2007)
    5. Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA. (PubMed id 11018027)1, 2, 9 Podust L.M.... Kim Y. (J. Biol. Chem. 2001)
    6. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. (PubMed id 15775988)1, 2, 9 Ohoka N.... Hayashi H. (EMBO J. 2005)
    7. Lithium response and genetic variation in the CREB family of genes. (PubMed id 18189280)1, 4, 9 Mamdani F....Turecki G. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008)
    8. Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome. (PubMed id 20873783)1, 2 Vaz Meirelles G.... Kobarg J. (J. Proteome Res. 2010)
    9. Association between genes of Disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses. (PubMed id 19251251)1, 4 Tomppo L....Peltonen L. (Biol. Psychiatry 2009)
    10. High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. (PubMed id 19453261)1, 4 Yerges L.M....Zmuda J.M. (J. Bone Miner. Res. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 468 HGNC: 786 AceView: ATF4andFLJ20232 Ensembl:ENSG00000128272 euGenes: HUgn468
    ECgene: ATF4 Kegg: 468 H-InvDB: ATF4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ATF4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ATF4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ATF4 gene:
    Search GeneIP for patents involving ATF4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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