ATF2

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions 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. The encoded protein may also be involved in cell's DNA damage response independent of its role in transcriptional regulation. Several alternatively spliced transcript variants have been found for this gene [provided by RefSeq, Jan 2014]

Activating Transcription Factor 2

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 (PubMed:10821277).
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.

Adipose tissue development Source: Ensembl
Amelogenesis Source: Ensembl
Cellular response to amino acid starvation Source: Reactome
Cellular response to DNA damage stimulus Source: UniProtKB
Fat cell differentiation Source: Ensembl
Histone H2B acetylation Source: ARUK-UCL
Histone H4 acetylation Source: ARUK-UCL
Intra-S DNA damage checkpoint Source: UniProtKB
Negative regulation of angiogenesis Source: BHF-UCL
Negative regulation of epithelial cell proliferation Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Outflow tract morphogenesis Source: Ensembl
Positive regulation of cardiac muscle myoblast proliferation Source: BHF-UCL
Positive regulation of DNA-binding transcription factor activity Source: UniProtKB
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of mitochondrial membrane permeability involved in apoptotic process Source: UniProtKB
Positive regulation of neuron apoptotic process Source: Ensembl
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Positive regulation of transforming growth factor beta2 production Source: Ensembl
Regulation of DNA-binding transcription factor activity Source: Reactome
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: BHF-UCL
Response to osmotic stress Source: UniProtKB
Response to water deprivation Source: Ensembl

Cytoplasm; Nucleus; Mitochondrion outer membrane. 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).

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 (PubMed:9430721, PubMed:12110590). Phosphorylated by PLK3 following hyperosmotic stress (PubMed:21098032). Also phosphorylated and activated by JNK and CaMK4 (PubMed:8855261). ATM-mediated phosphorylation at Ser-490 and Ser-498 stimulates its function in DNA damage response (PubMed:15916964). Phosphorylation at Ser-62, Thr-73 and Ser-121 activates its transcriptional activity (PubMed:15105425). Phosphorylation at Thr-69 or Thr-71 enhances acetylation of histones H2B and H4 (PubMed:10821277).