Cyclic AMP-dependent transcription factor ATF-4

Details

Name
Cyclic AMP-dependent transcription factor ATF-4
Synonyms
  • Activating transcription factor 4
  • cAMP-dependent transcription factor ATF-4
  • cAMP-responsive element-binding protein 2
  • CREB-2
  • CREB2
  • Cyclic AMP-responsive element-binding protein 2
  • DNA-binding protein TAXREB67
  • Tax-responsive enhancer element-binding protein 67
  • TaxREB67
  • TXREB
Gene Name
ATF4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021415|Cyclic AMP-dependent transcription factor ATF-4
MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFSSDKAKAGSSE
WLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALLGIDDLETMPDDLLTTLDDTC
DLFAPLVQETNKQPPQTVNPIGHLPESLTKPDQVAPFTFLQPLPLSPGVLSSTPDHSFSL
ELGSEVDITEGDRKPDYTAYVAMIPQCIKEEDTPSDNDSGICMSPESYLGSPQHSPSTRG
SPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGEKLDKKLKKMEQNKTAATRYRQKKR
AEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRVP
Number of residues
351
Molecular Weight
38589.14
Theoretical pI
Not Available
GO Classification
Functions
core promoter sequence-specific DNA binding / DNA binding / DNA binding transcription factor activity / leucine zipper domain binding / protein C-terminus binding / protein heterodimerization activity / protein kinase binding / RNA polymerase II proximal promoter sequence-specific DNA binding / RNA polymerase II transcription factor activity, sequence-specific DNA binding / RNA polymerase II transcription factor binding / sequence-specific DNA binding / transcription factor activity, RNA polymerase II transcription factor binding / transcription regulatory region DNA binding / transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding
Processes
cellular amino acid metabolic process / cellular response to amino acid starvation / cellular response to dopamine / cellular response to glucose starvation / cellular response to UV / circadian regulation of gene expression / gamma-aminobutyric acid signaling pathway / gluconeogenesis / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / mRNA transcription from RNA polymerase II promoter / negative regulation of oxidative stress-induced neuron death / negative regulation of potassium ion transport / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / positive regulation of apoptotic process / positive regulation of gene expression / positive regulation of neuron apoptotic process / positive regulation of transcription from RNA polymerase I promoter / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance / positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress / positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress / positive regulation of transcription from RNA polymerase II promoter in response to stress / positive regulation of transcription, DNA-templated / positive regulation of vascular endothelial growth factor production / regulation of transcription, DNA-templated / response to endoplasmic reticulum stress / response to manganese-induced endoplasmic reticulum stress / transcription from RNA polymerase II promoter
Components
ATF1-ATF4 transcription factor complex / ATF4-CREB1 transcription factor complex / CHOP-ATF4 complex / cytoplasm / dendrite membrane / Lewy body core / microtubule organizing center / neuron projection / nuclear periphery / nucleoplasm / nucleus / protein complex
General Function
Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to endoplasmic reticulum (ER) stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed:26086088).
Specific Function
Core promoter sequence-specific dna binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021416|Cyclic AMP-dependent transcription factor ATF-4 (ATF4)
ATGACCGAAATGAGCTTCCTGAGCAGCGAGGTGTTGGTGGGGGACTTGATGTCCCCCTTC
GACCAGTCGGGTTTGGGGGCTGAAGAAAGCCTAGGTCTCTTAGATGATTACCTGGAGGTG
GCCAAGCACTTCAAACCTCATGGGTTCTCCAGCGACAAGGCTAAGGCGGGCTCCTCCGAA
TGGCTGGCTGTGGATGGGTTGGTCAGTCCCTCCAACAACAGCAAGGAGGATGCCTTCTCC
GGGACAGATTGGATGTTGGAGAAAATGGATTTGAAGGAGTTCGACTTGGATGCCCTGTTG
GGTATAGATGACCTGGAAACCATGCCAGATGACCTTCTGACCACGTTGGATGACACTTGT
GATCTCTTTGCCCCCCTAGTCCAGGAGACTAATAAGCAGCCCCCCCAGACGGTGAACCCA
ATTGGCCATCTCCCAGAAAGTTTAACAAAACCCGACCAGGTTGCCCCCTTCACCTTCTTA
CAACCTCTTCCCCTTTCCCCAGGGGTCCTGTCCTCCACTCCAGATCATTCCTTTAGTTTA
GAGCTGGGCAGTGAAGTGGATATCACTGAAGGAGATAGGAAGCCAGACTACACTGCTTAC
GTTGCCATGATCCCTCAGTGCATAAAGGAGGAAGACACCCCTTCAGATAATGATAGTGGC
ATCTGTATGAGCCCAGAGTCCTATCTGGGGTCTCCTCAGCACAGCCCCTCTACCAGGGGC
TCTCCAAATAGGAGCCTCCCATCTCCAGGTGTTCTCTGTGGGTCTGCCCGTCCCAAACCT
TACGATCCTCCTGGAGAGAAGATGGTAGCAGCAAAAGTAAAGGGTGAGAAACTGGATAAG
AAGCTGAAAAAAATGGAGCAAAACAAGACAGCAGCCACTAGGTACCGCCAGAAGAAGAGG
GCGGAGCAGGAGGCTCTTACTGGTGAGTGCAAAGAGCTGGAAAAGAAGAACGAGGCTCTA
AAAGAGAGGGCGGATTCCCTGGCCAAGGAGATCCAGTACCTGAAAGATTTGATAGAAGAG
GTCCGCAAGGCAAGGGGGAAGAAAAGGGTCCCCTAG
Chromosome Location
22
Locus
22q13.1
External Identifiers
ResourceLink
UniProtKB IDP18848
UniProtKB Entry NameATF4_HUMAN
HGNC IDHGNC:786
General References
  1. Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K: Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I. J Virol. 1991 Mar;65(3):1420-6. [PubMed:1847461]
  2. Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM: Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4820-4. [PubMed:1534408]
  3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed:10591208]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Hai TW, Liu F, Coukos WJ, Green MR: Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083-90. [PubMed:2516827]
  6. Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H: TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005 Mar 23;24(6):1243-55. Epub 2005 Mar 10. [PubMed:15775988]
  7. Yu VW, Ambartsoumian G, Verlinden L, Moir JM, Prud'homme J, Gauthier C, Roughley PJ, St-Arnaud R: FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice. J Cell Biol. 2005 May 23;169(4):591-601. [PubMed:15911876]
  8. Sayer JA, Otto EA, O'Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C, Williams DS, Hoppe B, Kemper MJ, Neuhaus T, Parisi MA, Glass IA, Petry M, Kispert A, Gloy J, Ganner A, Walz G, Zhu X, Goldman D, Nurnberg P, Swaroop A, Leroux MR, Hildebrandt F: The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet. 2006 Jun;38(6):674-81. Epub 2006 May 7. [PubMed:16682973]
  9. Su N, Kilberg MS: C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem. 2008 Dec 12;283(50):35106-17. doi: 10.1074/jbc.M806874200. Epub 2008 Oct 21. [PubMed:18940792]
  10. Vaz Meirelles G, Ferreira Lanza DC, da Silva JC, Santana Bernachi J, Paes Leme AF, Kobarg J: Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome. J Proteome Res. 2010 Dec 3;9(12):6298-316. doi: 10.1021/pr100562w. Epub 2010 Oct 22. [PubMed:20873783]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  12. Shoval Y, Berissi H, Kimchi A, Pietrokovski S: New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. doi: 10.1371/journal.pone.0017344. [PubMed:21408167]
  13. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. [PubMed:25218447]
  14. D'Osualdo A, Anania VG, Yu K, Lill JR, Kaufman RJ, Matsuzawa S, Reed JC: Transcription Factor ATF4 Induces NLRP1 Inflammasome Expression during Endoplasmic Reticulum Stress. PLoS One. 2015 Jun 18;10(6):e0130635. doi: 10.1371/journal.pone.0130635. eCollection 2015. [PubMed:26086088]
  15. Podust LM, Krezel AM, Kim Y: Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA. J Biol Chem. 2001 Jan 5;276(1):505-13. [PubMed:11018027]
  16. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [PubMed:15461802]
  17. Ambivero CT, Cilenti L, Zervos AS: ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway. Biochim Biophys Acta. 2012 Dec;1823(12):2149-56. doi: 10.1016/j.bbamcr.2012.08.020. Epub 2012 Sep 6. [PubMed:22974638]
  18. Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23. [PubMed:28112733]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00852PseudoephedrineapprovedunknowninhibitorDetails