Cyclic AMP-dependent transcription factor ATF-2

Details

Name
Cyclic AMP-dependent transcription factor ATF-2
Synonyms
  • 2.3.1.48
  • Activating transcription factor 2
  • cAMP response element-binding protein CRE-BP1
  • cAMP-dependent transcription factor ATF-2
  • cAMP-responsive element-binding protein 2
  • CREB-2
  • CREB2
  • CREBP1
  • Cyclic AMP-responsive element-binding protein 2
  • HB16
  • Histone acetyltransferase ATF2
Gene Name
ATF2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008698|Cyclic AMP-dependent transcription factor ATF-2
MKFKLHVNSARQYKDLWNMSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARN
DSVIVADQTPTPTRFLKNCEEVGLFNELASPFENEFKKASEDDIKKMPLDLSPLATPIIR
SKIEEPSVVETTHQDSPLPHPESTTSDEKEVPLAQTAQPTSAIVRPASLQVPNVLLTSSD
SSVIIQQAVPSPTSSTVITQAPSSNRPIVPVPGPFPLLLHLPNGQTMPVAIPASITSSNV
HVPAAVPLVRPVTMVPSVPGIPGPSSPQPVQSEAKMRLKAALTQQHPPVTNGDTVKGHGS
GLVRTQSEESRPQSLQQPATSTTETPASPAHTTPQTQSTSGRRRRAANEDPDEKRRKFLE
RNRAAASRCRQKRKVWVQSLEKKAEDLSSLNGQLQSEVTLLRNEVAQLKQLLLAHKDCPV
TAMQKKSGYHTADKDDSSEDISVPSSPHTEAIQHSSVSTSNGVSSTSKAEAVATSVLTQM
ADQSTEPALSQIVMAPSSQSQPSGS
Number of residues
505
Molecular Weight
54536.94
Theoretical pI
Not Available
GO Classification
Functions
cAMP response element binding / cAMP response element binding protein binding / chromatin binding / DNA binding transcription factor activity / enhancer sequence-specific DNA binding / histone acetyltransferase activity / metal ion binding / protein heterodimerization activity / protein kinase binding / RNA polymerase II activating transcription factor binding / RNA polymerase II distal enhancer sequence-specific DNA binding / RNA polymerase II regulatory region sequence-specific DNA binding / transcription coactivator activity / transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding / transcription factor activity, RNA polymerase II transcription factor binding / transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding / transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding
Processes
adipose tissue development / amelogenesis / cellular response to DNA damage stimulus / fat cell differentiation / intra-S DNA damage checkpoint / negative regulation of angiogenesis / negative regulation of epithelial cell proliferation / negative regulation of transcription from RNA polymerase II promoter / outflow tract morphogenesis / positive regulation of cardiac muscle myoblast proliferation / positive regulation of DNA binding transcription factor activity / positive regulation of gene expression / positive regulation of mitochondrial membrane permeability involved in apoptotic process / positive regulation of neuron apoptotic process / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transforming growth factor beta2 production / regulation of DNA binding transcription factor activity / regulation of transcription from RNA polymerase II promoter / regulation of transcription, DNA-templated / response to osmotic stress / response to water deprivation
Components
cytoplasm / mitochondrial outer membrane / nucleoplasm / nucleus / site of double-strand break
General 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.
Specific Function
Camp response element binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0017561|Cyclic AMP-dependent transcription factor ATF-2 (ATF2)
ATGAAATTCAAGTTACATGTGAATTCTGCCAGGCAATACAAGGACCTGTGGAATATGAGT
GATGACAAACCCTTTCTATGTACTGCGCCTGGATGTGGCCAGCGTTTTACCAACGAGGAT
CATTTGGCTGTCCATAAACATAAACATGAGATGACACTGAAATTTGGTCCAGCACGTAAT
GACAGTGTCATTGTGGCTGATCAGACCCCAACACCAACAAGATTCTTGAAAAACTGTGAA
GAAGTGGGTTTGTTTAATGAGTTGGCGAGTCCATTTGAGAATGAATTCAAGAAAGCTTCA
GAAGATGACATTAAAAAAATGCCTCTAGATTTATCCCCTCTTGCAACACCTATCATAAGA
AGCAAAATTGAGGAGCCTTCTGTTGTAGAAACAACTCACCAGGATAGTCCTTTACCTCAC
CCAGAGTCTACTACCAGTGATGAGAAGGAAGTACCATTGGCACAAACTGCACAGCCCACA
TCAGCTATTGTTCGTCCAGCATCATTACAGGTTCCCAATGTGCTGCTTACAAGTTCTGAC
TCAAGTGTAATTATTCAGCAGGCAGTACCTTCACCAACCTCAAGTACTGTAATCACCCAG
GCACCATCCTCTAACAGGCCAATTGTCCCTGTACCAGGCCCATTTCCTCTTCTGTTACAT
CTTCCTAATGGACAAACCATGCCTGTTGCTATTCCTGCATCAATTACAAGTTCTAATGTG
CATGTTCCAGCTGCAGTCCCACTCGTTCGACCAGTCACCATGGTGCCTAGTGTTCCAGGA
ATCCCAGGTCCTTCCTCTCCCCAACCAGTACAGTCAGAAGCAAAAATGAGATTAAAAGCT
GCTTTGACCCAGCAACATCCTCCAGTTACCAATGGTGATACTGTCAAAGGTCATGGTAGC
GGATTGGTTAGGACTCAGTCAGAGGAATCTCGACCGCAGTCATTACAACAGCCAGCCACA
TCCACTACAGAAACTCCGGCTTCTCCAGCTCACACAACTCCACAGACCCAAAGTACAAGT
GGTCGTCGGAGAAGAGCAGCTAACGAAGATCCTGATGAAAAAAGGAGAAAGTTTTTAGAG
CGAAATAGAGCAGCAGCTTCAAGATGCCGACAAAAAAGGAAAGTCTGGGTTCAGTCTTTA
GAGAAGAAAGCTGAAGACTTGAGTTCATTAAATGGTCAGCTGCAGAGTGAAGTCACCCTG
CTGAGAAATGAAGTGGCACAGCTGAAACAGCTTCTTCTGGCTCATAAAGATTGCCCTGTA
ACCGCCATGCAGAAGAAATCTGGCTATCATACTGCTGATAAAGATGATAGTTCAGAAGAC
ATTTCAGTGCCGAGTAGTCCACATACAGAAGCTATACAGCATAGTTCGGTCAGCACATCC
AATGGAGTCAGTTCAACCTCCAAGGCAGAAGCTGTAGCCACTTCAGTCCTCACCCAGATG
GCGGACCAGAGTACAGAGCCTGCTCTTTCACAGATCGTTATGGCTCCTTCCTCCCAGTCA
CAGCCCTCAGGAAGTTGA
Chromosome Location
2
Locus
2q31.1
External Identifiers
ResourceLink
UniProtKB IDP15336
UniProtKB Entry NameATF2_HUMAN
HGNC IDHGNC:784
General References
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  2. Yang L, Lanier ER, Kraig E: Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus. J Immunol. 1997 Mar 15;158(6):2522-5. [Article]
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  7. Enslen H, Tokumitsu H, Stork PJ, Davis RJ, Soderling TR: Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10803-8. [Article]
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  9. Fukushima A, Okuda A, Nishimoto M, Seki N, Hori TA, Muramatsu M: Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity. J Biol Chem. 1998 Oct 2;273(40):25840-9. [Article]
  10. Kawasaki H, Schiltz L, Chiu R, Itakura K, Taira K, Nakatani Y, Yokoyama KK: ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature. 2000 May 11;405(6783):195-200. [Article]
  11. Ouwens DM, de Ruiter ND, van der Zon GC, Carter AP, Schouten J, van der Burgt C, Kooistra K, Bos JL, Maassen JA, van Dam H: Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. EMBO J. 2002 Jul 15;21(14):3782-93. [Article]
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  17. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
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  19. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  20. Yamasaki T, Takahashi A, Pan J, Yamaguchi N, Yokoyama KK: Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription. J Biol Chem. 2009 Mar 27;284(13):8567-81. doi: 10.1074/jbc.M808719200. Epub 2009 Jan 28. [Article]
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  26. Hsu CC, Hu CD: Critical role of N-terminal end-localized nuclear export signal in regulation of activating transcription factor 2 (ATF2) subcellular localization and transcriptional activity. J Biol Chem. 2012 Mar 9;287(11):8621-32. doi: 10.1074/jbc.M111.294272. Epub 2012 Jan 24. [Article]
  27. Lau E, Ronai ZA: ATF2 - at the crossroad of nuclear and cytosolic functions. J Cell Sci. 2012 Jun 15;125(Pt 12):2815-24. doi: 10.1242/jcs.095000. Epub 2012 Jun 8. [Article]
  28. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00852PseudoephedrineapprovedunknowninhibitorDetails