ATF2 (activating transcription factor 2)

Gene

• Entrez ID: 1386
• Gene name: Activating transcription factor 2
• Gene symbol: ATF2
• Synonyms: CRE-BP1, CREB-2, CREB2, HB16, TREB7
• Chromosome: 2
• Chromosome location: 2q31.1
• Summary: 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016080	hsa-miR-374b-5p	Sequencing	20371350
MIRT019034	hsa-miR-335-5p	Microarray	18185580
MIRT031029	hsa-miR-21-5p	Microarray	18591254
MIRT031297	hsa-miR-19b-3p	Sequencing	20371350
MIRT051336	hsa-miR-15a-5p	CLASH	23622248
MIRT733395	hsa-miR-204-3p	Luciferase reporter assay	27588402
MIRT733395	hsa-miR-204-3p	Luciferase reporter assay	27559047

Transcription factors

Transcription factor	Regulation	Reference
DDIT3	Repression	16164412
NR3C1	Repression	17016446
RB1	Unknown	7702750
SP1	Unknown	2145272

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	IDA	23729669
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IMP	2516827
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	19861239
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IC	19861239
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000987	Function	Cis-regulatory region sequence-specific DNA binding	IDA	2196176
GO:0001102	Function	RNA polymerase II activating transcription factor binding	IPI	19861239
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	16300731, 18671972, 19861239
GO:0003151	Process	Outflow tract morphogenesis	IEA
GO:0003682	Function	Chromatin binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	8798441
GO:0004402	Function	Histone acetyltransferase activity	TAS
GO:0005515	Function	Protein binding	IPI	8440710, 9748258, 10327051, 15105425, 15916964, 16511568, 18397884, 20102225, 20116378, 20195357, 20511396, 22439931, 24705354, 25416956, 25609649, 28514442, 31515488, 32296183
GO:0005634	Component	Nucleus	IDA	8798441, 18397884, 19861239, 21098032, 22304920
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	22304920
GO:0005741	Component	Mitochondrial outer membrane	IDA	22304920
GO:0006355	Process	Regulation of transcription, DNA-templated	IMP	22304920
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	19861239
GO:0006970	Process	Response to osmotic stress	IDA	21098032
GO:0006974	Process	Cellular response to DNA damage stimulus	IDA	22304920
GO:0006974	Process	Cellular response to DNA damage stimulus	IMP	15916964
GO:0008140	Function	CAMP response element binding protein binding	IDA	19861239
GO:0009414	Process	Response to water deprivation	IEA
GO:0010485	Function	H4 histone acetyltransferase activity	IDA	10821277
GO:0010628	Process	Positive regulation of gene expression	IMP	28977001
GO:0016525	Process	Negative regulation of angiogenesis	IMP	28977001
GO:0019901	Function	Protein kinase binding	IPI	21098032
GO:0031573	Process	Intra-S DNA damage checkpoint	IMP	15916964
GO:0032915	Process	Positive regulation of transforming growth factor beta2 production	IEA
GO:0035497	Function	CAMP response element binding	IBA	21873635
GO:0035497	Function	CAMP response element binding	IDA	19861239, 23729669
GO:0035861	Component	Site of double-strand break	IDA	15916964
GO:0043525	Process	Positive regulation of neuron apoptotic process	IEA
GO:0043967	Process	Histone H4 acetylation	IDA	10821277
GO:0043969	Process	Histone H2B acetylation	IDA	10821277
GO:0044013	Function	H2B histone acetyltransferase activity	IDA	10821277
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045444	Process	Fat cell differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	16300731, 18671972
GO:0046872	Function	Metal ion binding	IEA
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IEA
GO:0051090	Process	Regulation of DNA-binding transcription factor activity	TAS
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IMP	10821277
GO:0060612	Process	Adipose tissue development	IEA
GO:0097186	Process	Amelogenesis	IEA
GO:0110024	Process	Positive regulation of cardiac muscle myoblast proliferation	IDA	22982025
GO:1902110	Process	Positive regulation of mitochondrial membrane permeability involved in apoptotic process	IMP	22304920
GO:1902562	Component	H4 histone acetyltransferase complex	IDA	10821277
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 123811
• HGNC: 784
• e!Ensembl: ENSG00000115966

Protein

• UniProt ID: P15336
• Protein name: Cyclic AMP-dependent transcription factor ATF-2 (cAMP-dependent transcription factor ATF-2) (Activating transcription factor 2) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (HB16) (cAMP response element-binding protein CRE-BP1)
• Protein 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 (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.
• PDB: 1BHI, 1T2K, 4H36, 6ZQS, 6ZR5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00170	bZIP_1	350 → 413	bZIP transcription factor	Coiled-coil

• Sequence:

  MKFKLHVNSARQYKDLWNMSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARN
  DSVIVADQTPTPTRFLKNCEEVGLFNELASPFENEFKKASEDDIKKMPLDLSPLATPIIR
  SKIEEPSVVETTHQDSPLPHPESTTSDEKEVPLAQTAQPTSAIVRPASLQVPNVLLTSSD
  SSVIIQQAVPSPTSSTVITQAPSSNRPIVPVPGPFPLLLHLPNGQTMPVAIPASITSSNV
  HVPAAVPLVRPVTMVPSVPGIPGPSSPQPVQSEAKMRLKAALTQQHPPVTNGDTVKGHGS
  GLVRTQSEESRPQSLQQPATSTTETPASPAHTTPQTQSTSGRRRRAANEDPDEKRRKFLE
  RNRAAASRCRQKRKVWVQSLEKKAEDLSSLNGQLQSEVTLLRNEVAQLKQLLLAHKDCPV
  TAMQKKSGYHTADKDDSSEDISVPSSPHTEAIQHSSVSTSNGVSSTSKAEAVATSVLTQM
  ADQSTEPALSQIVMAPSSQSQPSGS

• Sequence length: 505