InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ATF2

Summary

InnateDB Protein

IDBP-245446.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ATF2

Protein Name

activating transcription factor 2

Synonyms

CRE-BP1; CREB-2; CREB2; HB16; TREB7;

Species

Homo sapiens

Ensembl Protein

ENSP00000376327

InnateDB Gene

IDBG-75609 (ATF2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10821277, ECO:0000269PubMed:15916964, ECO:0000269PubMed:18397884, ECO:0000269PubMed:22304920}.

Subcellular Localization

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).

Disease Associations

Tissue Specificity

Ubiquitously expressed, with more abundant expression in the brain.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 387 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	387 [view]
Protein-Protein	235 [view]
Protein-DNA	152 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001076	RNA polymerase II transcription factor binding transcription factor activity
GO:0001102	RNA polymerase II activating transcription factor binding
GO:0001228	RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0003713	transcription coactivator activity
GO:0004402	histone acetyltransferase activity
GO:0005515	protein binding
GO:0008140	cAMP response element binding protein binding
GO:0019901	protein kinase binding
GO:0035497	cAMP response element binding
GO:0043565	sequence-specific DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006325	chromatin organization
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:0006970	response to osmotic stress
GO:0006974	cellular response to DNA damage stimulus
GO:0016573	histone acetylation
GO:0031573	intra-S DNA damage checkpoint
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:1902110	positive regulation of mitochondrial membrane permeability involved in apoptotic process