ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. Many of these genes are important in cell growth and differentiation, and in stress and immune responses. ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. It is a stronger activator as a heterodimer with cJun than as a homodimer. Several isoforms of ATF2 arise by differential splicing. The stable native full length ATF2 is transcriptionally inactive as a result of an inhibitory direct intramolecular interaction of its carboxy terminal DNA binding domain with the amino terminal transactivation domain. Following dimerization ATF2 becomes a short lived protein that undergoes ubiquitination and proteolysis, seemingly in a protein phosphatase-dependent mechanism. Stimulation of the transcriptional activity of ATF2 occurs following cellular stress induced by several genotoxic agents, inflammatory cytokines, and UV irradiation. This activation requires phosphorylation of two threonine residues in ATF2 by both JNK/SAP kinase and p38 MAP kinase. ATF2 is abundantly expressed in brain.
Function:
Transcriptional activator, probably constitutive, which binds to the cAMP-responsive element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Interaction with JUN redirects JUN to bind to CRES preferentially over the 12-O-tetradecanoylphorbol-13-acetate response elements (TRES) as part of an ATF2/JUN complex.
Subunit:
Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity.
Subcellular Location:
Nucleus.
Tissue Specificity:
Abundant expression seen in the brain.
Post-translational modifications:
Phosphorylation of Thr-69 by MAPK14 and MAPK11, and at Thr-71 by MAPK1/ERK2, MAPK3/ERK1, MAPK11, MAPK12 and MAPK14 in response to external stimulus like insulin causes increased transcriptional activity. Phosphorylated by PLK3 following hyperosmotic stress. Also phosphorylated and activated by JNK and CaMK4.
Similarity:
Belongs to the bZIP family. ATF subfamily.
Contains 1 bZIP domain.
Contains 1 C2H2-type zinc finger.
SWISS:
P15336
Gene ID:
1386
Database links:
Entrez Gene: 1386 Human
Entrez Gene: 100047997 Mouse
Entrez Gene: 11909 Mouse
Entrez Gene: 81647 Rat
Omim: 123811 Human
SwissProt: P15336 Human
SwissProt: P16951 Mouse
SwissProt: Q00969 Rat
Unigene: 592510 Human
Unigene: 209903 Mouse
Unigene: 9825 Rat
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Sample:Liver (Mouse)Lysate at 40 ug
Primary: Anti-p-ATF2 (Ser322)(SL5169R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution
Predicted band size: 55kD
Observed band size: 55kD
Sample:
Cerebrum (Mouse)Lysate at 40 ug
Cerebellum (Mouse)Lysate at 40 ug
Primary: Anti-p-ATF2 (Ser322)(SL5169R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution
Predicted band size: 55kD
Observed band size: 55kD
Sample: Pancreas (Mouse)Lysate at 40 ug
Primary: Anti-p-ATF2 (Ser322)(SL5169R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution
Predicted band size: 55kD
Observed band size: 55kD
Paraformaldehyde-fixed, paraffin embedded (Rat brain); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (phospho-ATF2 (Ser322)) Polyclonal Antibody, Unconjugated (SL5169R) at 1:500 overnight at 4°C, followed by a conjugated secondary (sp-0023) for 20 minutes and DAB staining.
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