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ATF2 (activating transcription factor 2)

Identity

Other namesCREB1
CRE-BP1
CREB2
CREBP1
HB16
MGC111558
TREB7
Cyclic AMP-dependent transcription factor ATF-2
cAMP response element-binding protein CRE- BP1
HGNC (Hugo) ATF2
Location 2q31.1
Location_base_pair Starts at 175647252 and ends at 175741143 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 

DNA/RNA

 
  ATF2 gene structure based on data available in the Ensembl release 44. Upstream non-coding exons (green). Coding exons (pink), 3' untranslated sequence (red). The size of the exons in nucleotides is indicated below each exon. Exon number is indicated within the exon.
Description Gene size: 115.93Kb.
Transcription Initiation codon located in exon 4. Normal message is 2109 nucleotides. Some alternatively spliced RNA messages have been detected; but they are likely to represent splicing intermediates since no protein has been detected/expressed from these alternative messages in humans.

Protein

Note Protein of 505 aminoacids and a size of 52.27 kDa. Functions as a dimer, either homodimer or heterodimer with proteins of the jun family (e.g.: c-Jun, c-Fos).
 
Localisation Nuclear protein.
Function Transcription factor which binds to the cAMP-responsive element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'). ATF2 binds DNA as a dimer. The specificity of the DNA target sequence that is recognized by dimers containing ATF2 is different depending on whether it is a homodimer or it forms a heterodimer with another JUN protein.

Mutations

Note Lung cancer.
Somatic G to A transition in exon 10. Val258Ile Substitution.

Implicated in

Entity Clear Cell Sarcoma
Cytogenetics t(2;12)( q31.1;q13)
 
The arrow indicates the location of the breakpoint in chromosome 2. The ATF2 gene breaks within intron 6. In the translocation partner EWS the breakpoint occurs in intron 7. The transcript resulting from the hybrid gene fuses exon7 of EWS to exon 7 of ATF2.
Hybrid/Mutated Gene EWS-ATF2 fusion transcript.
Abnormal Protein The EWS-ATF2 fusion protein retains the ATF2 C-terminal region that contains the bZIP dimerization domain. But the fusion protein has lost the N-terminal domain of ATF2 that is kinase inducible. The N-terminal region of EWS is retained in the fusion protein but has lost both its RNA binding domain and its Zinc-finger Ran binding domain.
 
Structure of the EWS-ATF2 fusion protein.
Oncogenesis EWS-ATF2 may define a novel subset of clear cell sarcoma that occurs preferentially in the gastrointestinal tract and presents little or no melanocytic differentiation.
  

External links

Nomenclature
HGNC (Hugo)ATF2   784
Entrez_Gene (NCBI)ATF2  1386  activating transcription factor 2
Cards
AtlasATF2ID718ch2q31
GeneCards (Weizmann)ATF2
Ensembl (Hinxton)ENSG00000115966 [Gene_View]  ATF2 [Vega]
AceView (NCBI)ATF2
Genatlas (Paris)ATF2
euGene (Indiana)1386
SOURCE (Stanford)NM_001880
Genomic and cartography
GoldenPath (UCSC)ATF2  -  2q31.1   chr2:175647252-175741143 -  2q32   [Description]    (hg18-Mar_2006)
EnsemblATF2 - 2q32 [CytoView]
Mapping of homologs : NCBIATF2 [Mapview]
OMIM123811   
Gene and transcription
Gene : Genbank (Entrez)AI200584 AK128731 AY029364 BC026175 BC107698
Reference sequence (RefSeq transcript) :SRSNM_001880
Reference transcript : EntrezNM_001880
RefSeq genomic : SRSAC_000045 AC_000134 NC_000002 NT_005403 NW_001838863 NW_921585
RefSeq genomic : EntrezAC_000045 AC_000134 NC_000002 NT_005403 NW_001838863 NW_921585
Consensus coding sequences : CCDS NCBIATF2
Cluster EST : UnigeneHs.592510 [ SRS ] Hs.592510 [ NCBI ]
Alternative Splicing : Fast-db (Paris)13090
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP15336 (SRS) P15336 (Expasy) P15336 (Uniprot)
With graphics : InterProP15336
Splice isoforms : VarSplice FASTAP15336(VarSplice FASTA)
Domaine pattern : Prosite (SRS)BZIP (PS50217)    BZIP_BASIC (PS00036)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domain pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (SRS)bZIP_1    TF_bZIP    TF_cAMP-dep    Znf_C2H2    Znf_C2H2-like   
Domains : Interpro (EBI)bZIP_1    TF_bZIP    TF_cAMP-dep    Znf_C2H2    Znf_C2H2-like   
Related proteins : CluSTrP15336
Domain families : Pfam SRSbZIP_1 (PF00170)    zf-C2H2 (PF00096)   
Domain families : Pfam SangerbZIP_1 (PF00170)    zf-C2H2 (PF00096)   
Domain families : Pfam NCBIpfam00170    pfam00096   
Domain families : Smart EMBLBRLZ (SM00338)ZnF_C2H2 (SM00355)
Blocks (Seattle)P15336
Crystal structure of protein : PDB SRS1BHI    1T2K   
Crystal structure of protein : PDBSum1BHI    1T2K   
Crystal structure of protein : IMB1BHI    1T2K   
Crystal structure of protein : PDB RSDB1BHI    1T2K   
HPRD00443
Protein Interaction databases
DIP (DOE-UCLA)P15336
IntAct (EBI)P15336
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIATF2
SNP : GeneSNP UtahATF2
SNP : HGBaseATF2
Genetic variants : HAPMAPATF2
Mutations and Diseases : HGMDATF2
Hereditary diseases : OMIM123811   
Hereditary diseases : GENETests123811   
Diseases : Genetic AssociationATF2
General knowledge
Homologs : HomoloGeneATF2
Homology/Alignments : Family Browser UCSCATF2
Phylogenetic Trees/Animal Genes : TreeFamATF2
Chemical/Protein Interactions : CTD1386
Keywords Ontology : AmiGOtranscription factor activity  RNA polymerase II transcription factor activity  transcription coactivator activity  intracellular  nucleus  cytosol  transcription  regulation of transcription, DNA-dependent  zinc ion binding  sequence-specific DNA binding  metal ion binding  protein dimerization activity  
Keywords Ontology : EGO-EBItranscription factor activity  RNA polymerase II transcription factor activity  transcription coactivator activity  intracellular  nucleus  cytosol  transcription  regulation of transcription, DNA-dependent  zinc ion binding  sequence-specific DNA binding  metal ion binding  protein dimerization activity  
Pathways : BIOCARTAThe 4-1BB-dependent immune response [Genes]    Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    ALK in cardiac myocytes [Genes]    MAPKinase Signaling Pathway [Genes]    p38 MAPK Signaling Pathway [Genes]    The information-processing pathway at the IFN-beta enhancer [Genes]   
Pathways : KEGGMAPK signaling pathway
Other databases
Probes
Probes : ImagenesATF2 Related clones (RZPD - Berlin)
Literature
PubMed90 Pubmed reference(s) in Entrez
PubGeneATF2

Bibliography

ATF-2 contains a phosphorylation-dependent transcriptional activation domain.
Livingstone C, Patel G, Jones N
The EMBO journal. 1995 ; 14 (8) : 1785-1797.
PMID 7737129
 
Stability of the ATF2 transcription factor is regulated by phosphorylation and dephosphorylation.
Fuchs SY, Tappin I, Ronai Z
The Journal of biological chemistry. 2000 ; 275 (17) : 12560-12564.
PMID 10777545
 
Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment.
Bhoumik A, Ivanov V, Ronai Z
Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (2) : 331-342.
PMID 11234888
 
Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB.
Mayr BM, Canettieri G, Montminy MR
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (19) : 10936-10941.
PMID 11535812
 
Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis.
van Dam H, Castellazzi M
Oncogene. 2001 ; 20 (19) : 2453-2464.
PMID 11402340
 
Infrequent mutations of the activating transcription factor-2 gene in human lung cancer, neuroblastoma and breast cancer.
Woo IS, Kohno T, Inoue K, Ishii S, Yokota J
International journal of oncology. 2002 ; 20 (3) : 527-531.
PMID 11836564
 
Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL.
Przybylski GK, Dik WA, Wanzeck J, Grabarczyk P, Majunke S, Martin-Subero JI, Siebert R, Dlken G, Ludwig WD, Verhaaf B, van Dongen JJ, Schmidt CA, Langerak AW
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (2) : 201-208.
PMID 15668700
 
EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation.
Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M
Clinical cancer research : an official journal of the American Association for Cancer Research. 2006 ; 12 (18) : 5356-5362.
PMID 17000668
 
Mutual regulation of c-Jun and ATF2 by transcriptional activation and subcellular localization.
Liu H, Deng X, Shyu YJ, Li JJ, Taparowsky EJ, Hu CD
The EMBO journal. 2006 ; 25 (5) : 1058-1069.
PMID 16511568
 
Functional interaction of CREB binding protein (CBP) with nuclear transport proteins and modulation by HDAC inhibitors.
Ryan CM, Harries JC, Kindle KB, Collins HM, Heery DM
Cell cycle (Georgetown, Tex.). 2006 ; 5 (18) : 2146-2152.
PMID 16969114
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2007Pedro A Lazo, Ana Sevilla
Instituto de Biologia Molecular y Celular del Cancer, CSIC-Universidad de Salamanca, Salamanca, Spain

Citation

This paper should be referenced as such :
Lazo PA, Sevilla A . ATF2 (activating transcription factor 2). Atlas Genet Cytogenet Oncol Haematol. July 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/ATF2ID718ch2q31.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jun 27 16:37:36 CEST 2009

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