ATF2 Antibody – Rabbit Polyclonal

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It forms a homodimer or a heterodimer with c-Jun and stimulates CRE-dependent transcription. This protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

Function: Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro. In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. Ref.12 Ref.15 Ref.18 Ref.27

Catalytic activity: Acetyl-CoA + [histone] = CoA + acetyl-[histone].

Subunit structure: Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Heterodimerization is essential for its transcriptional activity. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity. Interacts with the HK1/VDAC1 complex. Interacts with NBN, MRE11A, XPO1, KAT5 and CUL3. Ref.11 Ref.15 Ref.18 Ref.27 Ref.28

Subcellular location: Nucleus. Cytoplasm. Mitochondrion outer membrane. Note: Shuttles between the cytoplasm and the nucleus and heterodimerization with JUN is essential for the nuclear localization. Localization to the cytoplasm is observed under conditions of cellular stress and in disease states. Localizes at the mitochondrial outer membrane in response to genotoxic stress. Phosphorylation at Thr-52 is required for its nuclear localization and negatively regulates its mitochondrial localization. Co-localizes with the MRN complex in the IR-induced foci (IRIF). Ref.14 Ref.15 Ref.18 Ref.22 Ref.25 Ref.27 Ref.28

Tissue specificity: Ubiquitously expressed, with more abundant expression in the brain.

Domain: The nuclear export signal 1 (N-NES) negatively regulates its nuclear localization and transcriptional activity.

Post-translational modification: 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. ATM-mediated phosphorylation at Ser-490 and Ser-498 stimulates its function in DNA damage response. Phosphorylation at Ser-62, Thr-73 and Ser-121 activates its transcriptional activity. Phosphorylation at Thr-69 or Thr-71 enhances its histone acetyltransferase (HAT) activity. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.22 Ref.25 Ref.27

Sequence similarities: Belongs to the bZIP family. ATF subfamily.Contains 1 bZIP (basic-leucine zipper) domain.Contains 1 C2H2-type zinc finger.

Sequence caution: The sequence AAY17203.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.The sequence AAY17207.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.