Human Gene ATF2 (ENST00000409833.5) Description and Page Index
  Description: Homo sapiens activating transcription factor 2 (ATF2), transcript variant 6, mRNA. (from RefSeq NM_001256094)
RefSeq Summary (NM_001256094): This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It forms a homodimer or a heterodimer with c-Jun and stimulates CRE-dependent transcription. This 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. The encoded protein may also be involved in cell's DNA damage response independent of its role in transcriptional regulation. Several alternatively spliced transcript variants have been found for this gene [provided by RefSeq, Jan 2014].
Gencode Transcript: ENST00000409833.5
Gencode Gene: ENSG00000115966.17
Transcript (Including UTRs)
   Position: hg38 chr2:175,114,243-175,168,169 Size: 53,927 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg38 chr2:175,114,686-175,136,443 Size: 21,758 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:175,114,243-175,168,169)mRNA (may differ from genome)Protein (209 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ATF2_HUMAN
DESCRIPTION: RecName: Full=Cyclic AMP-dependent transcription factor ATF-2; Short=cAMP-dependent transcription factor ATF-2; AltName: Full=Activating transcription factor 2; AltName: Full=Cyclic AMP-responsive element-binding protein 2; Short=CREB-2; Short=cAMP-responsive element-binding protein 2; AltName: Full=HB16; AltName: Full=cAMP response element-binding protein CRE-BP1;
FUNCTION: Transcriptional activator, probably constitutive, which binds to the cAMP-responsive element (CRE) (consensus: 5'- GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Interaction with JUN redirects JUN to bind to CRES preferentially over the 12-O-tetradecanoylphorbol-13-acetate response elements (TRES) as part of an ATF2/JUN complex.
SUBUNIT: Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity.
INTERACTION: P01100:FOS; NbExp=4; IntAct=EBI-1170906, EBI-852851; P05412:JUN; NbExp=4; IntAct=EBI-1170906, EBI-852823; Q15532:SS18; NbExp=2; IntAct=EBI-1170906, EBI-2560599; A4PIW0:SYT-SSX2; NbExp=11; IntAct=EBI-1170906, EBI-6050533; Q99986:VRK1; NbExp=5; IntAct=EBI-1170906, EBI-1769146;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Abundant expression seen in the brain.
PTM: Phosphorylation of Thr-69 by MAPK14 and MAPK11, and at Thr-71 by MAPK1/ERK2, MAPK3/ERK1, MAPK11, MAPK12 and MAPK14 in response to external stimulus like insulin causes increased transcriptional activity. Phosphorylated by PLK3 following hyperosmotic stress. Also phosphorylated and activated by JNK and CaMK4.
SIMILARITY: Belongs to the bZIP family. ATF subfamily.
SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain.
SIMILARITY: Contains 1 C2H2-type zinc finger.
CAUTION: It is uncertain whether Met-1 or Met-19 is the initiator.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ATF2ID718ch2q31.html";

-  MalaCards Disease Associations
  MalaCards Gene Search: ATF2
Diseases sorted by gene-association score: metaphyseal chondrodysplasia, murk jansen type (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.70 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 463.89 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -72.70262-0.277 Picture PostScript Text
3' UTR -78.40443-0.177 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004827 - bZIP
IPR016378 - TF_cAMP-dep
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00170 - bZIP transcription factor

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1BHI
- NMR MuPIT

1T2K
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P15336
FrontTopSide
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0001158 enhancer sequence-specific DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0003713 transcription coactivator activity
GO:0004402 histone acetyltransferase activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0008140 cAMP response element binding protein binding
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0035497 cAMP response element binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0003151 outflow tract morphogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0006970 response to osmotic stress
GO:0006974 cellular response to DNA damage stimulus
GO:0009414 response to water deprivation
GO:0010628 positive regulation of gene expression
GO:0016525 negative regulation of angiogenesis
GO:0016573 histone acetylation
GO:0031573 intra-S DNA damage checkpoint
GO:0032915 positive regulation of transforming growth factor beta2 production
GO:0043525 positive regulation of neuron apoptotic process
GO:0045444 fat cell differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050680 negative regulation of epithelial cell proliferation
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060612 adipose tissue development
GO:0097186 amelogenesis
GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0016020 membrane
GO:0035861 site of double-strand break


-  Descriptions from all associated GenBank mRNAs
  BX648469 - Homo sapiens mRNA; cDNA DKFZp686L15145 (from clone DKFZp686L15145).
AK128731 - Homo sapiens cDNA FLJ46899 fis, clone UTERU3022588, highly similar to Cyclic AMP-dependent transcription factor ATF-2.
BC107698 - Homo sapiens activating transcription factor 2, mRNA (cDNA clone MGC:111558 IMAGE:6456836), complete cds.
U16028 - Human CRE-BP1 transcription factor mRNA, complete cds.
BC130335 - Homo sapiens activating transcription factor 2, mRNA (cDNA clone MGC:163207 IMAGE:40146366), complete cds.
BC130337 - Homo sapiens activating transcription factor 2, mRNA (cDNA clone MGC:163209 IMAGE:40146368), complete cds.
X15875 - Human mRNA for cAMP response element (CRE-BP1) binding protein.
DQ003036 - Homo sapiens activating transcription factor 2 splice variant ATF2-var0 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003037 - Homo sapiens activating transcription factor 2 splice variant ATF2-var1 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003038 - Homo sapiens activating transcription factor 2 splice variant ATF2-var2 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003039 - Homo sapiens activating transcription factor 2 splice variant ATF2-var3 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003040 - Homo sapiens activating transcription factor 2 splice variant ATF2-var4 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003041 - Homo sapiens activating transcription factor 2 splice variant ATF2-var5 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003042 - Homo sapiens activating transcription factor 2 splice variant ATF2-var6 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003043 - Homo sapiens activating transcription factor 2 splice variant ATF2-var7 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003044 - Homo sapiens activating transcription factor 2 splice variant ATF2-var8 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003045 - Homo sapiens activating transcription factor 2 splice variant ATF2-var9 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003046 - Homo sapiens activating transcription factor 2 splice variant ATF2-var10 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003047 - Homo sapiens activating transcription factor 2 splice variant ATF2-var11 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003048 - Homo sapiens activating transcription factor 2 splice variant ATF2-var12 (ATF2) mRNA, complete cds, alternatively spliced.
DQ003049 - Homo sapiens activating transcription factor 2 splice variant ATF2-var13 (ATF2) mRNA, complete cds, alternatively spliced.
AY029364 - Homo sapiens activating transcription factor 2 splice variant (ATF2) mRNA, complete cds.
HQ258270 - Synthetic construct Homo sapiens clone IMAGE:100072579 activating transcription factor 2 (ATF2) (ATF2) gene, encodes complete protein.
KJ890967 - Synthetic construct Homo sapiens clone ccsbBroadEn_00361 ATF2 gene, encodes complete protein.
AB384878 - Synthetic construct DNA, clone: pF1KB3962, Homo sapiens ATF2 gene for cyclic AMP-dependent transcription factor ATF-2, complete cds, without stop codon, in Flexi system.
BC026175 - Homo sapiens activating transcription factor 2, mRNA (cDNA clone IMAGE:4308091), complete cds.
KJ901355 - Synthetic construct Homo sapiens clone ccsbBroadEn_10749 ATF2 gene, encodes complete protein.
JD326302 - Sequence 307326 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P15336 (Reactome details) participates in the following event(s):

R-HSA-168440 Formation of Activated Protein 1 (AP-1) complex. ATF2/c-JUN heterodimer.
R-HSA-8944397 p-T69,T71-ATF2 binds PTEN gene promoter
R-HSA-168053 Phosphorylated MAPKs phosphorylate ATF-2
R-HSA-3318415 ATF2 acetylates histone H2B, H4
R-HSA-9009371 Binding of AP1 transcriptional activator complexes to CCND1 promoter
R-HSA-6806412 TP53 and AP-1 bind the MSH2 promoter
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-6807070 PTEN Regulation
R-HSA-3214847 HATs acetylate histones
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
R-HSA-450294 MAP kinase activation
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-8939211 ESR-mediated signaling
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-448424 Interleukin-17 signaling
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975871 MyD88 cascade initiated on plasma membrane
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-4839726 Chromatin organization
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-212436 Generic Transcription Pathway
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-449147 Signaling by Interleukins
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade
R-HSA-162582 Signal Transduction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168249 Innate Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-74160 Gene expression (Transcription)
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A1L3Z2, ATF2_HUMAN, CREB2, CREBP1, D3DPE9, NM_001256094, P15336, Q13000, Q4ZFU9, Q53RY2, uc002ujy.1, uc002ujy.2, uc002ujy.3
UCSC ID: uc002ujy.3
RefSeq Accession: NM_001256094
Protein: P15336 (aka ATF2_HUMAN)
CCDS: CCDS58739.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.