ATF3

Protein-coding gene in the species Homo sapiens
ATF3
Identifiers
AliasesATF3, activating transcription factor 3
External IDsOMIM: 603148; MGI: 109384; HomoloGene: 1265; GeneCards: ATF3; OMA:ATF3 - orthologs
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for ATF3
Genomic location for ATF3
Band1q32.3Start212,565,334 bp[1]
End212,620,777 bp[1]
Gene location (Mouse)
Chromosome 1 (mouse)
Chr.Chromosome 1 (mouse)[2]
Chromosome 1 (mouse)
Genomic location for ATF3
Genomic location for ATF3
Band1 H6|1 96.28 cMStart190,902,493 bp[2]
End190,950,236 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • vena cava

  • gastric mucosa

  • gallbladder

  • saphenous vein

  • trachea

  • urethra

  • pericardium

  • left uterine tube

  • cardia

  • mucosa of urinary bladder
Top expressed in
  • plantaris muscle

  • islet of Langerhans

  • intestinal villus

  • jejunum

  • sciatic nerve

  • endocardial cushion

  • left colon

  • atrioventricular valve

  • mucous cell of stomach

  • spermatocyte
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • transcription cis-regulatory region binding
  • protein homodimerization activity
  • protein binding
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
  • protein heterodimerization activity
  • identical protein binding
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • DNA binding
  • transcription corepressor activity
  • DNA-binding transcription factor activity
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • nucleolus
  • nucleoplasm
  • CHOP-ATF3 complex
  • nucleus
Biological process
  • regulation of transcription by RNA polymerase II
  • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
  • positive regulation of cell population proliferation
  • skeletal muscle cell differentiation
  • regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance
  • gluconeogenesis
  • cellular response to amino acid starvation
  • negative regulation of transcription, DNA-templated
  • regulation of transcription, DNA-templated
  • positive regulation of TRAIL-activated apoptotic signaling pathway
  • transcription, DNA-templated
  • positive regulation of gene expression
  • PERK-mediated unfolded protein response
  • positive regulation of transcription by RNA polymerase II
  • negative regulation of ERK1 and ERK2 cascade
  • negative regulation of transcription by RNA polymerase II
  • endoplasmic reticulum unfolded protein response
  • transcription by RNA polymerase II
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

467

11910

Ensembl

ENSG00000162772

ENSMUSG00000026628

UniProt

P18847

Q60765

RefSeq (mRNA)
NM_001030287
NM_001040619
NM_001206484
NM_001206485
NM_001206486

NM_001206488
NM_001674
NM_004024

NM_007498

RefSeq (protein)
NP_001025458
NP_001035709
NP_001193413
NP_001193415
NP_001193417

NP_001665

NP_031524

Location (UCSC)Chr 1: 212.57 – 212.62 MbChr 1: 190.9 – 190.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.[5]

Function

Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. Multiple transcript variants encoding two different isoforms have been found for this gene. The longer isoform represses rather than activates transcription from promoters with ATF binding elements. The shorter isoform (deltaZip2) lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription, it is presumed, by sequestering inhibitory co-factors away from the promoter. It is possible that alternative splicing of the ATF3 gene may be physiologically important in the regulation of target genes.[6]

Clinical significance

ATF-3 is induced upon physiological stress in various tissues.[7] It is also a marker of regeneration following injury of dorsal root ganglion neurons, as injured regenerating neurons activate this transcription factor. [8] Functional validation studies have shown that ATF3 can promote regeneration of peripheral neurons, but is not capable of promoting regeneration of central nervous system neurons. [9]

See also

Interactions

ATF3 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162772 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026628 – 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. ^ Chen BP, Liang G, Whelan J, Hai T (June 1994). "ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms". The Journal of Biological Chemistry. 269 (22): 15819–26. doi:10.1016/S0021-9258(17)40754-X. PMID 7515060.
  6. ^ "Entrez Gene: ATF3 activating transcription factor 3".
  7. ^ Chen BP, Wolfgang CD, Hai T (March 1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
  8. ^ Lindå H, Sköld MK, Ochsmann T (2011). "Activating transcription factor 3, a useful marker for regenerative response after nerve root injury". Frontiers in Neurology. 2: 30. doi:10.3389/fneur.2011.00030. PMC 3099310. PMID 21629765.
  9. ^ Mahar M, Cavalli V (June 2018). "Intrinsic mechanisms of neuronal axon regeneration". Nature Reviews. Neuroscience. 19 (6): 323–337. doi:10.1038/s41583-018-0001-8. PMC 5987780. PMID 29666508.
  10. ^ Pearson AG, Gray CW, Pearson JF, Greenwood JM, During MJ, Dragunow M (December 2003). "ATF3 enhances c-Jun-mediated neurite sprouting". Brain Research. Molecular Brain Research. 120 (1): 38–45. doi:10.1016/j.molbrainres.2003.09.014. PMID 14667575.
  11. ^ a b Chen BP, Wolfgang CD, Hai T (March 1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
  12. ^ Hai T, Curran T (May 1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proceedings of the National Academy of Sciences of the United States of America. 88 (9): 3720–4. Bibcode:1991PNAS...88.3720H. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
  13. ^ Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Molecular Endocrinology. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
  14. ^ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
  15. ^ Yan C, Wang H, Boyd DD (March 2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". The Journal of Biological Chemistry. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID 11792711.
  16. ^ Kang Y, Chen CR, Massagué J (April 2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Molecular Cell. 11 (4): 915–26. doi:10.1016/s1097-2765(03)00109-6. PMID 12718878.

Further reading

  • Hai TW, Liu F, Coukos WJ, Green MR (December 1989). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes & Development. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID 2516827.
  • Kaszubska W, Hooft van Huijsduijnen R, Ghersa P, DeRaemy-Schenk AM, Chen BP, Hai T, DeLamarter JF, Whelan J (November 1993). "Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines". Molecular and Cellular Biology. 13 (11): 7180–90. doi:10.1128/MCB.13.11.7180. PMC 364779. PMID 7692236.
  • Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Molecular Endocrinology. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
  • Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T (January 1996). "ATF3 gene. Genomic organization, promoter, and regulation". The Journal of Biological Chemistry. 271 (3): 1695–701. doi:10.1074/jbc.271.3.1695. PMID 8576171.
  • Chen BP, Wolfgang CD, Hai T (March 1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
  • Hagmeyer BM, Duyndam MC, Angel P, de Groot RP, Verlaan M, Elfferich P, van der Eb A, Zantema A (March 1996). "Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3". Oncogene. 12 (5): 1025–32. PMID 8649793.
  • Allan AL, Albanese C, Pestell RG, LaMarre J (July 2001). "Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes". The Journal of Biological Chemistry. 276 (29): 27272–80. doi:10.1074/jbc.M103196200. PMID 11375399.
  • Zhang C, Kawauchi J, Adachi MT, Hashimoto Y, Oshiro S, Aso T, Kitajima S (December 2001). "Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine". Biochemical and Biophysical Research Communications. 289 (3): 718–24. doi:10.1006/bbrc.2001.6044. PMID 11726207.
  • Yan C, Wang H, Boyd DD (March 2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". The Journal of Biological Chemistry. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID 11792711.
  • Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles". Journal of Biomedical Science. 9 (1): 82–96. doi:10.1007/BF02256581. PMID 11810028.
  • Hashimoto Y, Zhang C, Kawauchi J, Imoto I, Adachi MT, Inazawa J, Amagasa T, Hai T, Kitajima S (June 2002). "An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli". Nucleic Acids Research. 30 (11): 2398–406. doi:10.1093/nar/30.11.2398. PMC 117192. PMID 12034827.
  • Kawauchi J, Zhang C, Nobori K, Hashimoto Y, Adachi MT, Noda A, Sunamori M, Kitajima S (October 2002). "Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription". The Journal of Biological Chemistry. 277 (41): 39025–34. doi:10.1074/jbc.M202974200. PMID 12161427.
  • Zhang C, Gao C, Kawauchi J, Hashimoto Y, Tsuchida N, Kitajima S (October 2002). "Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53". Biochemical and Biophysical Research Communications. 297 (5): 1302–10. doi:10.1016/S0006-291X(02)02382-3. PMID 12372430.
  • Fan F, Jin S, Amundson SA, Tong T, Fan W, Zhao H, Zhu X, Mazzacurati L, Li X, Petrik KL, Fornace AJ, Rajasekaran B, Zhan Q (October 2002). "ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth". Oncogene. 21 (49): 7488–96. doi:10.1038/sj.onc.1205896. PMID 12386811.
  • Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M (October 2002). "ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3". Journal of Molecular and Cellular Cardiology. 34 (10): 1387–97. doi:10.1006/jmcc.2002.2091. PMID 12392999.
  • Kang Y, Chen CR, Massagué J (April 2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Molecular Cell. 11 (4): 915–26. doi:10.1016/S1097-2765(03)00109-6. PMID 12718878.
  • Newman JR, Keating AE (June 2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science. 300 (5628): 2097–101. Bibcode:2003Sci...300.2097N. doi:10.1126/science.1084648. PMID 12805554. S2CID 36715183.
  • Kool J, Hamdi M, Cornelissen-Steijger P, van der Eb AJ, Terleth C, van Dam H (July 2003). "Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2". Oncogene. 22 (27): 4235–42. doi:10.1038/sj.onc.1206611. PMID 12833146.

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


  • v
  • t
  • e
InhibitsIs activated by
not
  • 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
  1. ^ Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim MS, Kim SW, Park IS, Youn JH, Lee KU (December 2007). "Essential role of mitochondrial function in adiponectin synthesis in adipocytes". Diabetes. 56 (12): 2973–81. doi:10.2337/db07-0510. PMID 17827403.