Activating transcription factor 2

Protein-coding gene in the species Homo sapiens

ATF2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1BHI, 1T2K, 4H36

Identifiers
AliasesATF2, CRE-BP1, CREB-2, CREB2, HB16, TREB7, activating transcription factor 2
External IDsOMIM: 123811 MGI: 109349 HomoloGene: 31061 GeneCards: ATF2
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for ATF2
Genomic location for ATF2
Band2q31.1Start175,072,250 bp[1]
End175,168,382 bp[1]
Gene location (Mouse)
Chromosome 2 (mouse)
Chr.Chromosome 2 (mouse)[2]
Chromosome 2 (mouse)
Genomic location for ATF2
Genomic location for ATF2
Band2|2 C3Start73,816,509 bp[2]
End73,892,639 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • endothelial cell

  • germinal epithelium

  • Brodmann area 23

  • corpus epididymis

  • caput epididymis

  • ganglionic eminence

  • seminal vesicula

  • parietal pleura

  • superficial temporal artery

  • retinal pigment epithelium
Top expressed in
  • paraventricular nucleus of hypothalamus

  • medial dorsal nucleus

  • dorsomedial hypothalamic nucleus

  • habenula

  • arcuate nucleus

  • ventral tegmental area

  • olfactory tubercle

  • subiculum

  • lateral hypothalamus

  • ventromedial nucleus
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • transferase activity
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • DNA binding
  • sequence-specific DNA binding
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • cAMP response element binding protein binding
  • DNA-binding transcription factor activity
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • transcription coactivator activity
  • chromatin binding
  • metal ion binding
  • protein binding
  • cis-regulatory region sequence-specific DNA binding
  • nucleic acid binding
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
  • protein kinase binding
  • cAMP response element binding
  • histone acetyltransferase activity
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • transcription factor binding
  • protein heterodimerization activity
Cellular component
  • cytoplasm
  • membrane
  • nucleoplasm
  • mitochondrial outer membrane
  • mitochondrion
  • nucleus
  • site of double-strand break
Biological process
  • regulation of transcription, DNA-templated
  • regulation of transcription by RNA polymerase II
  • mitotic intra-S DNA damage checkpoint signaling
  • outflow tract morphogenesis
  • response to water deprivation
  • positive regulation of DNA-binding transcription factor activity
  • negative regulation of transcription by RNA polymerase II
  • transcription by RNA polymerase II
  • positive regulation of transforming growth factor beta2 production
  • transcription, DNA-templated
  • cellular response to DNA damage stimulus
  • response to osmotic stress
  • positive regulation of neuron apoptotic process
  • regulation of DNA-binding transcription factor activity
  • positive regulation of mitochondrial membrane permeability involved in apoptotic process
  • negative regulation of epithelial cell proliferation
  • adipose tissue development
  • fat cell differentiation
  • positive regulation of transcription by RNA polymerase II
  • amelogenesis
  • histone acetylation
  • positive regulation of cardiac muscle myoblast proliferation
  • positive regulation of gene expression
  • negative regulation of angiogenesis
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

1386

11909

Ensembl

ENSG00000115966

ENSMUSG00000027104

UniProt

P15336

P16951

RefSeq (mRNA)
NM_001256090
NM_001256091
NM_001256092
NM_001256093
NM_001256094

NM_001880

NM_001025093
NM_001284369
NM_001284370
NM_001284371
NM_001284372

NM_001284373
NM_001284374
NM_001284376
NM_009715

RefSeq (protein)
NP_001243019
NP_001243020
NP_001243021
NP_001243022
NP_001243023

NP_001871

NP_001020264
NP_001271298
NP_001271299
NP_001271300
NP_001271301

NP_001271302
NP_001271303
NP_001271305
NP_033845

Location (UCSC)Chr 2: 175.07 – 175.17 MbChr 2: 73.82 – 73.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.[5]

Function

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun. The 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. Additional transcript variants have been identified but their biological validity has not been determined.[5]

The gene atf2 is located at human chromosome 2q32.[6] The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton.[7] ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK.[8] ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated.[9]

Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors.[10][11] ATF-2 may mediate oncogenesis caused by mutant Ras protein[12] and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells.

ATF2 has also been shown to be phosphorylated at its C-terminal (serine 472 and 480 in mouse; serine 490 and 498 in human) by ATM upon double-stranded breaks.[13] Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.

Interactions

Activating transcription factor 2 has been shown to interact with

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115966 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027104 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: ATF2 activating transcription factor 2".
  6. ^ Ozawa K, Sudo T, Soeda E, Yoshida MC, Ishii S (1991). "Assignment of the human CREB2 (CRE-BP1) gene to 2q32". Genomics. 10 (4): 1103–4. doi:10.1016/0888-7543(91)90210-6. PMID 1833307.
  7. ^ Reimold AM, Grusby MJ, Kosaras B, Fries JW, Mori R, Maniwa S, Clauss IM, Collins T, Sidman RL, Glimcher MJ, Glimcher LH (1996). "Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice". Nature. 379 (6562): 262–5. Bibcode:1996Natur.379..262R. doi:10.1038/379262a0. PMID 8538792. S2CID 4326412.
  8. ^ Gupta S, Campbell D, Dérijard B, Davis RJ (1995). "Transcription factor ATF2 regulation by the JNK signal transduction pathway". Science. 267 (5196): 389–93. Bibcode:1995Sci...267..389G. doi:10.1126/science.7824938. PMID 7824938. S2CID 40268838.
  9. ^ Yamasaki T, Takahashi A, Pan J, Yamaguchi N, Yokoyama KK (March 2009). "Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription". J. Biol. Chem. 284 (13): 8567–81. doi:10.1074/jbc.M808719200. PMC 2659215. PMID 19176525.
  10. ^ Leslie MC, Bar-Eli M (2005). "Regulation of gene expression in melanoma: new approaches for treatment". J. Cell. Biochem. 94 (1): 25–38. doi:10.1002/jcb.20296. PMID 15523674. S2CID 23515325.
  11. ^ Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H, Zoumpourlis V (2004). "Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors". Cancer Res. 64 (23): 8573–84. doi:10.1158/0008-5472.CAN-03-0955. PMID 15574764. S2CID 14845890.
  12. ^ Vlahopoulos SA, Logotheti S, Mikas D, Giarika A, Gorgoulis V, Zoumpourlis V (17 March 2008). "The role of ATF-2 in oncogenesis". BioEssays. 30 (4): 314–27. doi:10.1002/bies.20734. PMID 18348191. S2CID 678541.
  13. ^ Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, Ronai Z (May 2005). "ATM-dependent phosphorylation of ATF2 is required for the DNA damage response". Mol. Cell. 18 (5): 577–87. doi:10.1016/j.molcel.2005.04.015. PMC 2954254. PMID 15916964.
  14. ^ Newell CL, Deisseroth AB, Lopez-Berestein G (July 1994). "Interaction of nuclear proteins with an AP-1/CRE-like promoter sequence in the human TNF-alpha gene". J. Leukoc. Biol. 56 (1): 27–35. doi:10.1002/jlb.56.1.27. PMID 8027667. S2CID 85570533.
  15. ^ Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH (April 1990). "A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain". Mol. Cell. Biol. 10 (4): 1347–57. doi:10.1128/MCB.10.4.1347. PMC 362236. PMID 2320002.
  16. ^ Hai T, Curran T (May 1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. Bibcode:1991PNAS...88.3720H. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
  17. ^ a b Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (August 1998). "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Res. 26 (16): 3854–61. doi:10.1093/nar/26.16.3854. PMC 147779. PMID 9685505.
  18. ^ Sano Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S (October 1998). "CBP alleviates the intramolecular inhibition of ATF-2 function". J. Biol. Chem. 273 (44): 29098–105. doi:10.1074/jbc.273.44.29098. PMID 9786917.
  19. ^ Murata T, Shinozuka Y, Obata Y, Yokoyama KK (May 2008). "Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in Escherichia coli by Jun N-terminal kinase 1". Anal. Biochem. 376 (1): 115–21. doi:10.1016/j.ab.2008.01.038. PMID 18307971.
  20. ^ a b Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (March 1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". J. Biol. Chem. 270 (13): 7420–6. doi:10.1074/jbc.270.13.7420. PMID 7535770.
  21. ^ a b Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
  22. ^ a b Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. Bibcode:1997PNAS...94.7337T. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
  23. ^ Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. PMID 9405416.
  24. ^ Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, Ishii S (March 1999). "ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling". J. Biol. Chem. 274 (13): 8949–57. doi:10.1074/jbc.274.13.8949. PMID 10085140.
  25. ^ Hong S, Choi HM, Park MJ, Kim YH, Choi YH, Kim HH, Choi YH, Cheong J (April 2004). "Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid". J. Biol. Chem. 279 (17): 16996–7003. doi:10.1074/jbc.M311752200. PMID 14734562.
  26. ^ Cho SG, Bhoumik A, Broday L, Ivanov V, Rosenstein B, Ronai Z (December 2001). "TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage". Mol. Cell. Biol. 21 (24): 8398–413. doi:10.1128/MCB.21.24.8398-8413.2001. PMC 100004. PMID 11713276.
  27. ^ Firestein R, Feuerstein N (March 1998). "Association of activating transcription factor 2 (ATF2) with the ubiquitin-conjugating enzyme hUBC9. Implication of the ubiquitin/proteasome pathway in regulation of ATF2 in T cells". J. Biol. Chem. 273 (10): 5892–902. doi:10.1074/jbc.273.10.5892. PMID 9488727.

External links

Further reading

  • Denys H, Desmet R, Stragier M, Vergison R, Lemahieu SF (1977). "Cystitis emphysematosa". Acta Urol Belg. 45 (4): 327–31. PMID 602896.
  • Kim SJ, Wagner S, Liu F, O'Reilly MA, Robbins PD, Green MR (1992). "Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2". Nature. 358 (6384): 331–4. Bibcode:1992Natur.358..331K. doi:10.1038/358331a0. PMID 1641004. S2CID 9770957.
  • Hai T, Curran T (1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. Bibcode:1991PNAS...88.3720H. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
  • Hoeffler JP, Lustbader JW, Chen CY (1991). "Identification of multiple nuclear factors that interact with cyclic adenosine 3',5'-monophosphate response element-binding protein and activating transcription factor-2 by protein-protein interactions". Mol. Endocrinol. 5 (2): 256–66. doi:10.1210/mend-5-2-256. PMID 1828107.
  • Ozawa K, Sudo T, Soeda E, Yoshida MC, Ishii S (1991). "Assignment of the human CREB2 (CRE-BP1) gene to 2q32". Genomics. 10 (4): 1103–4. doi:10.1016/0888-7543(91)90210-6. PMID 1833307.
  • Diep A, Li C, Klisak I, Mohandas T, Sparkes RS, Gaynor R, Lusis AJ (1991). "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32". Genomics. 11 (4): 1161–3. doi:10.1016/0888-7543(91)90047-I. PMID 1838349.
  • Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH (1990). "A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain". Mol. Cell. Biol. 10 (4): 1347–57. doi:10.1128/MCB.10.4.1347. PMC 362236. PMID 2320002.
  • Gonzalez GA, Yamamoto KK, Fischer WH, Karr D, Menzel P, Biggs W, Vale WW, Montminy MR (1989). "A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence". Nature. 337 (6209): 749–52. Bibcode:1989Natur.337..749G. doi:10.1038/337749a0. PMID 2521922. S2CID 4345950.
  • Maekawa T, Sakura H, Kanei-Ishii C, Sudo T, Yoshimura T, Fujisawa J, Yoshida M, Ishii S (1989). "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain". EMBO J. 8 (7): 2023–8. doi:10.1002/j.1460-2075.1989.tb03610.x. PMC 401081. PMID 2529117.
  • Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". J. Biol. Chem. 270 (13): 7420–6. doi:10.1074/jbc.270.13.7420. PMID 7535770.
  • Livingstone C, Patel G, Jones N (1995). "ATF-2 contains a phosphorylation-dependent transcriptional activation domain". EMBO J. 14 (8): 1785–97. doi:10.1002/j.1460-2075.1995.tb07167.x. PMC 398272. PMID 7737129.
  • van Dam H, Wilhelm D, Herr I, Steffen A, Herrlich P, Angel P (1995). "ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents". EMBO J. 14 (8): 1798–811. doi:10.1002/j.1460-2075.1995.tb07168.x. PMC 398273. PMID 7737130.
  • Zhou Q, Gedrich RW, Engel DA (1995). "Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB". J. Virol. 69 (7): 4323–30. doi:10.1128/JVI.69.7.4323-4330.1995. PMC 189172. PMID 7769693.
  • Newell CL, Deisseroth AB, Lopez-Berestein G (1994). "Interaction of nuclear proteins with an AP-1/CRE-like promoter sequence in the human TNF-alpha gene". J. Leukoc. Biol. 56 (1): 27–35. doi:10.1002/jlb.56.1.27. PMID 8027667. S2CID 85570533.
  • Nomura N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S (1993). "Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1". J. Biol. Chem. 268 (6): 4259–66. doi:10.1016/S0021-9258(18)53604-8. PMID 8440710.
  • Martin ML, Lieberman PM, Curran T (1996). "Fos-Jun dimerization promotes interaction of the basic region with TFIIE-34 and TFIIF". Mol. Cell. Biol. 16 (5): 2110–8. doi:10.1128/mcb.16.5.2110. PMC 231198. PMID 8628277.
  • Yang L, Lanier ER, Kraig E (1997). "Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus". J. Immunol. 158 (6): 2522–5. doi:10.4049/jimmunol.158.6.2522. PMID 9058782. S2CID 29299351.
  • Shuman JD, Cheong J, Coligan JE (1997). "ATF-2 and C/EBPalpha can form a heterodimeric DNA binding complex in vitro. Functional implications for transcriptional regulation". J. Biol. Chem. 272 (19): 12793–800. doi:10.1074/jbc.272.19.12793. PMID 9139739.
  • Fukunaga R, Hunter T (1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
  • Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC, Young PR (1997). "Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles". Biochem. Biophys. Res. Commun. 235 (3): 533–8. doi:10.1006/bbrc.1997.6849. PMID 9207191.

External links

  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-2


  • v
  • t
  • e
  • 1bhi: STRUCTURE OF TRANSACTIVATION DOMAIN OF CRE-BP1/ATF-2, NMR, 20 STRUCTURES
    1bhi: STRUCTURE OF TRANSACTIVATION DOMAIN OF CRE-BP1/ATF-2, NMR, 20 STRUCTURES
  • 1t2k: Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA
    1t2k: Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies