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ATF5 (activating transcription factor 5)

Written2010-06Arthur KK Ching, Nathalie Wong
Department of Anatomical, Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong

(Note : for Links provided by Atlas : click)


Other aliasATFX
LocusID (NCBI) 22809
Atlas_Id 50361
Location 19q13.33  [Link to chromosome band 19q13]
Location_base_pair Starts at and ends at bp from pter
Local_order Refer to mapping diagram.
  Mapping diagram. Base on Human Mar. 2006 (NCBI36/hg18) Assembly.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATF5 (19q13.33) / ATF5 (19q13.33)ATF5 (19q13.33) / UBE2V1 (20q13.13)ATF5 (19q13.33) / VPS13D (1p36.22)
HNRNPAB (5q35.3) / ATF5 (19q13.33)PUM2 (2p24.1) / ATF5 (19q13.33)SLC12A2 (5q23.3) / ATF5 (19q13.33)


  DNA structure diagram. Relative size of the 4 exons of ATF5. Exon 1 and 2 are untranslated exons (NCBI reference sequence NM_012068.4). Blue area is non-coding region and pink is coding region.
Description The ATF5 gene spans a total genomic size of 5219 bases and is composed of four exons.
Transcription The human ATF5 transcript is 2268 bp in size (NM_012068.4) and contains 4 exons. Exon 1 and 2 are non-coding exons and the size of open reading frame is 849 bp.


  Protein structure diagram.
Description ATF5 consists of 282 amino acid with MW of 30.69 kDa (NCBI reference sequence NP_036200.2).
Expression Northern blot analysis revealed ubiquitous expression of ATF5, with highest levels in liver, lung, adipose tissue, heart, and skeletal muscle.
Localisation Nucleus and cytoplasm.
Function ATF5 is a member of basic-region leucine zipper (bZIP) proteins family which binds the cAMP response element (CRE) consensus sequence: 5'GTGACGT(C/A)(G/A). This sequence is present in many viral and cellular promoters. ATF within or between subgroups can form homo- or hetero-dimer through the bZIP domain and the dimer can then bind to the DNA through the basic-motif and function as a transcription factor. Recently, another novel ATF5 consensus DNA binding sequence (CYTCTYCCTTW) was found in C6 glioma and MCF7 using a cyclic amplification and selection of targets (CASTing) approach (Li et al., 2009).
ATF5 is linked to many cellular function including cell cycle progression, metabolite homeostasis (Al Sarraj et al., 2005; Watatani et al., 2007), cellular differentiation and apoptosis. It involves in the proliferation and differentiation of neural cells (Angelastro et al., 2003; Angelastro et al., 2005; Mason et al., 2005) and has been shown to take part in the skeletal development of mouse limb (Shinomura et al., 2006; Satake at al., 2009). Data from various groups also suggested that ATF5 can function as anti-apoptotic factor (Devireddy et al., 2001; Persengiev et al., 2002; Nishioka et al., 2009).
Coimmunoprecipitation and GST pull-down analyses confirmed the association of the C-terminal bZIP motif of ATF5 with the PRL-1 PTPase domain and adjacent residues of PTP4A1 in vitro. SDS-PAGE analysis showed that PRL-1 dephosphorylates ATF5 in vitro (Peters et al., 2001).
ATF5 has been shown to interact with various proteins including Cyclin D3 (Liu et al., 2004), GABAB receptors (White et al., 2000), HTLV-1 viral protein Tax (Forgacs et al., 2005), E2 ubiguitin-conjugating enzyme Cdc34, PRL-1 and DISC1 (Morris et al., 2003; Fujii et al., 2007; Tomppo et al., 2009). It is a target of Cdc34-dependent ubiquitin-mediated proteolysis (Pati et al., 1999). Study indicates that during stress condition, eIF2 is phosphorylated and subsequently direct ATF5 translation in cell (Watatani et al., 2008; Zhou et al., 2008). Recent study of the promoter of ATF5 also suggested that its transcription is regulated by EBF1 (Wei et al., 2010).
Homology ATF5 gene is highly conserved in mammals. Protein identity percentage of human ATF5 compared with chimpanzee, cow, mouse, and rat is 98.9, 88.0, 87.5 and 88.9 respectively.


Germinal Unknown.
Somatic Exon2 Leu141Phe, Exon2 Val257Met and Exon2 Arg275Trp.

Implicated in

Entity Various cancers
Note ATF5 is showed to be overexpressed in various cancers by TMA (tissue microarray) that includes breast cancer, glioblastomas, adenocarcinomas, transitional cell carcinomas, squamous cell carcinomas and metastatic carcinomas of various origin (Monaco et al., 2007). However, in hepatocellular carcinoma, ATF5 expression is down-regulated, suggesting that role of ATF5 in tumor is highly depending on the tumor type.
Entity Glioma
Note ATF5 has been shown to be highly expressed in perinecrotic palisades, the most aggressive forms of malignant gliomas. In a study of 28 tumors without perinecrotic palisades, the level of ATF5 expression together with 4 other genes, negatively correlated with time of patient survival. Interference of ATF5 expression in glioma cell lines causes apoptosis but not in cultured astrocytes. These findings suggested that ATF5 plays a role in maintaining cell survival in glioma.
Cytogenetics Unknown.
Hybrid/Mutated Gene Unknown.
Abnormal Protein Unknown.
Entity Hepatocellular carcinoma
Note A study has showed that ATF5 is down-regulated in 60 out of 77 cases in HCC, as in contrast to adult normal liver where expression of ATF5 is particularly high. Gene expression profiling was also done by ectopic re-expression of ATF5 suggesting cell cycle, actin skeleton regulation, MAPK signaling and focal adhesion are the pathways modulated by ATF5. These findings suggested that ATF5 down regulation may contribute to the development of HCC. The inactivation mechanisms of ATF5 involve epigenetic silencing and chromosome copy number loss.


Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP.
Al Sarraj J, Vinson C, Thiel G.
Biol Chem. 2005 Sep;386(9):873-9.
PMID 16164412
Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5.
Angelastro JM, Canoll PD, Kuo J, Weicker M, Costa A, Bruce JN, Greene LA.
Oncogene. 2006 Feb 9;25(6):907-16.
PMID 16170340
Identification of RASSF1A modulated genes in nasopharyngeal carcinoma.
Chow LS, Lam CW, Chan SY, Tsao SW, To KF, Tong SF, Hung WK, Dammann R, Huang DP, Lo KW.
Oncogene. 2006 Jan 12;25(2):310-6.
PMID 16116475
Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation.
Devireddy LR, Teodoro JG, Richard FA, Green MR.
Science. 2001 Aug 3;293(5531):829-34.
PMID 11486081
Histology-based expression profiling yields novel prognostic markers in human glioblastoma.
Dong S, Nutt CL, Betensky RA, Stemmer-Rachamimov AO, Denko NC, Ligon KL, Rowitch DH, Louis DN.
J Neuropathol Exp Neurol. 2005 Nov;64(11):948-55.
PMID 16254489
The bZIP transcription factor ATFx binds human T-cell leukemia virus type 1 (HTLV-1) Tax and represses HTLV-1 long terminal repeat-mediated transcription.
Forgacs E, Gupta SK, Kerry JA, Semmes OJ.
J Virol. 2005 Jun;79(11):6932-9.
PMID 15890932
Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest.
Gho JW, Ip WK, Chan KY, Law PT, Lai PB, Wong N.
Cancer Res. 2008 Aug 15;68(16):6743-51.
PMID 18701499
The transcription factor ATF5: role in neurodevelopment and neural tumors.
Greene LA, Lee HY, Angelastro JM.
J Neurochem. 2009 Jan;108(1):11-22. Epub 2008 Nov 15. (REVIEW)
PMID 19046351
Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells.
Li G, Li W, Angelastro JM, Greene LA, Liu DX.
Mol Cancer Res. 2009 Jun;7(6):933-43. Epub 2009 Jun 16.
PMID 19531563
Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity.
Liu W, Sun M, Jiang J, Shen X, Sun Q, Liu W, Shen H, Gu J.
Biochem Biophys Res Commun. 2004 Sep 3;321(4):954-60.
PMID 15358120
ATF5 regulates the proliferation and differentiation of oligodendrocytes.
Mason JL, Angelastro JM, Ignatova TN, Kukekov VG, Lin G, Greene LA, Goldman JE.
Mol Cell Neurosci. 2005 Jul;29(3):372-80.
PMID 15950153
The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines.
Monaco SE, Angelastro JM, Szabolcs M, Greene LA.
Int J Cancer. 2007 May 1;120(9):1883-90.
PMID 17266024
DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.
Morris JA, Kandpal G, Ma L, Austin CP.
Hum Mol Genet. 2003 Jul 1;12(13):1591-608.
PMID 12812986
Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis.
Pati D, Meistrich ML, Plon SE.
Mol Cell Biol. 1999 Jul;19(7):5001-13.
PMID 10373550
Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors.
Persengiev SP, Devireddy LR, Green MR.
Genes Dev. 2002 Jul 15;16(14):1806-14.
PMID 12130540
ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase.
Peters CS, Liang X, Li S, Kannan S, Peng Y, Taub R, Diamond RH.
J Biol Chem. 2001 Apr 27;276(17):13718-26. Epub 2001 Jan 22.
PMID 11278933
Spatio-temporal expression of activating transcription factor 5 in the skeletal development of mouse limb.
Satake H, Ito K, Takahara M, Furukawa T, Takagi M, Ogino T, Shinomura T.
Dev Growth Differ. 2009 Sep;51(7):669-76.
PMID 19712269
Association between genes of Disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses.
Tomppo L, Hennah W, Lahermo P, Loukola A, Tuulio-Henriksson A, Suvisaari J, Partonen T, Ekelund J, Lonnqvist J, Peltonen L.
Biol Psychiatry. 2009 Jun 15;65(12):1055-62. Epub 2009 Feb 28.
PMID 19251251
Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region.
Watatani Y, Ichikawa K, Nakanishi N, Fujimoto M, Takeda H, Kimura N, Hirose H, Takahashi S, Takahashi Y.
J Biol Chem. 2008 Feb 1;283(5):2543-53. Epub 2007 Nov 30.
PMID 18055463
Identification and characterization of the promoter of human ATF5 gene.
Wei Y, Ge Y, Zhou F, Chen H, Cui C, Liu D, Yang Z, Wu G, Gu J, Jiang J.
J Biochem. 2010 Apr 27. [Epub ahead of print]
PMID 20423929
The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx.
White JH, McIllhinney RA, Wise A, Ciruela F, Chan WY, Emson PC, Billinton A, Marshall FH.
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13967-72.
PMID 11087824
Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions.
Zhou D, Palam LR, Jiang L, Narasimhan J, Staschke KA, Wek RC.
J Biol Chem. 2008 Mar 14;283(11):7064-73. Epub 2008 Jan 14.
PMID 18195013


This paper should be referenced as such :
Ching, AKK ; Wong, N
ATF5 (activating transcription factor 5)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(3):252-254.
Free journal version : [ pdf ]   [ DOI ]
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External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)22809
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:28:52 CEST 2018

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