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P15336 (ATF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclic AMP-dependent transcription factor ATF-2

Short name=cAMP-dependent transcription factor ATF-2
EC=2.3.1.48
Alternative name(s):
Activating transcription factor 2
Cyclic AMP-responsive element-binding protein 2
Short name=CREB-2
Short name=cAMP-responsive element-binding protein 2
HB16
Histone acetyltransferase ATF2
cAMP response element-binding protein CRE-BP1
Gene names
Name:ATF2
Synonyms:CREB2, CREBP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro. In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. Ref.12 Ref.15 Ref.18 Ref.27

Catalytic activity

Acetyl-CoA + [histone] = CoA + acetyl-[histone].

Subunit structure

Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Heterodimerization is essential for its transcriptional activity. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity. Interacts with the HK1/VDAC1 complex. Interacts with NBN, MRE11A, XPO1, KAT5 and CUL3. Ref.11 Ref.15 Ref.18 Ref.27 Ref.28

Subcellular location

Nucleus. Cytoplasm. Mitochondrion outer membrane. Note: Shuttles between the cytoplasm and the nucleus and heterodimerization with JUN is essential for the nuclear localization. Localization to the cytoplasm is observed under conditions of cellular stress and in disease states. Localizes at the mitochondrial outer membrane in response to genotoxic stress. Phosphorylation at Thr-52 is required for its nuclear localization and negatively regulates its mitochondrial localization. Co-localizes with the MRN complex in the IR-induced foci (IRIF). Ref.14 Ref.15 Ref.18 Ref.22 Ref.25 Ref.27 Ref.28

Tissue specificity

Ubiquitously expressed, with more abundant expression in the brain.

Domain

The nuclear export signal 1 (N-NES) negatively regulates its nuclear localization and transcriptional activity.

Post-translational modification

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. ATM-mediated phosphorylation at Ser-490 and Ser-498 stimulates its function in DNA damage response. Phosphorylation at Ser-62, Thr-73 and Ser-121 activates its transcriptional activity. Phosphorylation at Thr-69 or Thr-71 enhances its histone acetyltransferase (HAT) activity. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.22 Ref.25 Ref.27

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Contains 1 C2H2-type zinc finger.

Sequence caution

The sequence AAY17203.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAY17207.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processDNA damage
Transcription
Transcription regulation
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

adipose tissue development

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from direct assay Ref.27. Source: UniProtKB

chromatin organization

Traceable author statement. Source: Reactome

fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

histone acetylation

Inferred from direct assay Ref.12. Source: GOC

innate immune response

Traceable author statement. Source: Reactome

intra-S DNA damage checkpoint

Inferred from mutant phenotype Ref.15. Source: UniProtKB

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitochondrial membrane permeability involved in apoptotic process

Inferred from mutant phenotype Ref.27. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of transforming growth factor beta2 production

Inferred from electronic annotation. Source: Ensembl

regulation of sequence-specific DNA binding transcription factor activity

Traceable author statement. Source: Reactome

regulation of transcription from RNA polymerase II promoter

Inferred by curator PubMed 19861239. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.27. Source: UniProtKB

response to osmotic stress

Inferred from direct assay Ref.25. Source: UniProtKB

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Inferred by curator PubMed 19861239. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay Ref.27. Source: UniProtKB

mitochondrial outer membrane

Inferred from direct assay Ref.27. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.18Ref.25Ref.27. Source: UniProtKB

site of double-strand break

Inferred from direct assay Ref.15. Source: UniProtKB

   Molecular_functionRNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 19861239. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II distal enhancer sequence-specific DNA binding

Inferred from direct assay PubMed 19861239. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred by curator PubMed 19861239. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity

Inferred by curator PubMed 19861239. Source: BHF-UCL

cAMP response element binding

Inferred from direct assay PubMed 19861239. Source: BHF-UCL

cAMP response element binding protein binding

Inferred from direct assay PubMed 19861239. Source: BHF-UCL

chromatin binding

Inferred from electronic annotation. Source: Ensembl

histone acetyltransferase activity

Inferred from direct assay Ref.12. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.15Ref.18PubMed 8440710Ref.11. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.25. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 8798441. Source: MGI

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15336-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P15336-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-176: Missing.
     177-185: TSSDSSVII → MSTAYFQMM
Isoform 3 (identifier: P15336-3)

The sequence of this isoform differs from the canonical sequence as follows:
     210-505: Missing.
Isoform 4 (identifier: P15336-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MKFKLHVNSARQYKDLWNMSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARNDSVIVA → MYCAWMWP
Isoform 5 (identifier: P15336-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
Isoform 6 (identifier: P15336-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     34-394: Missing.
Isoform 7 (identifier: P15336-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     210-237: PVPGPFPLLLHLPNGQTMPVAIPASITS → SFDQSPWCLVFQESQVLPLPNQYSQKQK
     238-505: Missing.
Isoform 8 (identifier: P15336-8)

Also known as: ATF2-small;

The sequence of this isoform differs from the canonical sequence as follows:
     34-394: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 505505Cyclic AMP-dependent transcription factor ATF-2
PRO_0000076577

Regions

Domain352 – 41564bZIP
Zinc finger25 – 4925C2H2-type
Region296 – 2994Essential for its histone acetyltransferase activity
Region354 – 37421Basic motif By similarity
Region380 – 40829Leucine-zipper By similarity
Motif1 – 77Nuclear export signal 1 (N-NES)
Motif405 – 41410Nuclear export signal 2 (C-NES)

Amino acid modifications

Modified residue521Phosphothreonine; by PKC/PRKCH Ref.27
Modified residue621Phosphoserine; by VRK1 Ref.14
Modified residue691Phosphothreonine; by MAPK11 and MAPK14 Ref.10 Ref.13 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26
Modified residue711Phosphothreonine; by MAPK1, MAPK3, MAPK11, MAPK12, MAPK14 and PLK3 Ref.10 Ref.13 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26
Modified residue731Phosphothreonine; by VRK1 Ref.14
Modified residue901Phosphoserine Ref.26
Modified residue1121Phosphoserine Ref.20 Ref.23 Ref.24 Ref.26
Modified residue1161Phosphothreonine Ref.24
Modified residue1211Phosphoserine; by PKC/PRKCA and PKC/PRKCB Ref.22
Modified residue3281Phosphoserine Ref.19
Modified residue3401Phosphoserine; by PKC/PRKCA and PKC/PRKCB Ref.22
Modified residue3571N6-acetyllysine Ref.16
Modified residue3671Phosphoserine; by PKC/PRKCA and PKC/PRKCB Ref.22
Modified residue3741N6-acetyllysine Ref.16
Modified residue4901Phosphoserine; by ATM Ref.15
Modified residue4981Phosphoserine; by ATM Ref.15

Natural variations

Alternative sequence1 – 176176Missing in isoform 2.
VSP_000587
Alternative sequence1 – 6666MKFKL…SVIVA → MYCAWMWP in isoform 4.
VSP_046959
Alternative sequence1 – 1818Missing in isoform 5, isoform 6 and isoform 7.
VSP_046960
Alternative sequence34 – 394361Missing in isoform 6 and isoform 8.
VSP_047593
Alternative sequence177 – 1859TSSDSSVII → MSTAYFQMM in isoform 2.
VSP_000588
Alternative sequence210 – 505296Missing in isoform 3.
VSP_045161
Alternative sequence210 – 23728PVPGP…ASITS → SFDQSPWCLVFQESQVLPLP NQYSQKQK in isoform 7.
VSP_047594
Alternative sequence238 – 505268Missing in isoform 7.
VSP_047595
Natural variant3521D → H in a breast cancer sample; somatic mutation. Ref.31
VAR_035999

Experimental info

Mutagenesis691T → A: Weak histone acetyltransferase activity. Ref.12
Mutagenesis711T → A: Impairs phosphorylation by PLK3. Weak histone acetyltransferase activity. Ref.12 Ref.25
Mutagenesis1211S → A: Reduced phosphorylation and repression of c-Jun-mediated activation of transcription.
Sequence conflict2091V → L in AAB64017. Ref.2
Sequence conflict2231N → S in CAA33886. Ref.1
Sequence conflict2231N → S in AAY17203. Ref.4
Sequence conflict2231N → S in AAY17207. Ref.4
Sequence conflict2231N → S in AAY17215. Ref.4
Sequence conflict3111R → L in AAB64017. Ref.2

Secondary structure

......... 505
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 25, 2008. Version 4.
Checksum: 0190EEFAEC8891A7

FASTA50554,537
        10         20         30         40         50         60 
MKFKLHVNSA RQYKDLWNMS DDKPFLCTAP GCGQRFTNED HLAVHKHKHE MTLKFGPARN 

        70         80         90        100        110        120 
DSVIVADQTP TPTRFLKNCE EVGLFNELAS PFENEFKKAS EDDIKKMPLD LSPLATPIIR 

       130        140        150        160        170        180 
SKIEEPSVVE TTHQDSPLPH PESTTSDEKE VPLAQTAQPT SAIVRPASLQ VPNVLLTSSD 

       190        200        210        220        230        240 
SSVIIQQAVP SPTSSTVITQ APSSNRPIVP VPGPFPLLLH LPNGQTMPVA IPASITSSNV 

       250        260        270        280        290        300 
HVPAAVPLVR PVTMVPSVPG IPGPSSPQPV QSEAKMRLKA ALTQQHPPVT NGDTVKGHGS 

       310        320        330        340        350        360 
GLVRTQSEES RPQSLQQPAT STTETPASPA HTTPQTQSTS GRRRRAANED PDEKRRKFLE 

       370        380        390        400        410        420 
RNRAAASRCR QKRKVWVQSL EKKAEDLSSL NGQLQSEVTL LRNEVAQLKQ LLLAHKDCPV 

       430        440        450        460        470        480 
TAMQKKSGYH TADKDDSSED ISVPSSPHTE AIQHSSVSTS NGVSSTSKAE AVATSVLTQM 

       490        500 
ADQSTEPALS QIVMAPSSQS QPSGS 

« Hide

Isoform 2 [UniParc].

Checksum: FA37EF544698FEFA
Show »

FASTA32935,044
Isoform 3 [UniParc].

Checksum: A26AF07CA5D8D5E7
Show »

FASTA20923,050
Isoform 4 [UniParc].

Checksum: 344628FF8F94AAED
Show »

FASTA44748,013
Isoform 5 [UniParc].

Checksum: 58ADD6240D6270E8
Show »

FASTA48752,277
Isoform 6 [UniParc].

Checksum: B9D2E843EB156412
Show »

FASTA12613,149
Isoform 7 [UniParc].

Checksum: 6DA3C87FF1008F68
Show »

FASTA21924,097
Isoform 8 (ATF2-small) [UniParc].

Checksum: 8B7F060B955355C7
Show »

FASTA14415,409

References

« Hide 'large scale' references
[1]"Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain."
Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S.
EMBO J. 8:2023-2028(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[2]"Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus."
Yang L., Lanier E.R., Kraig E.
J. Immunol. 158:2522-2525(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Thymus.
[3]"Characterization and functional analysis of cAMP response element modulator protein and activating transcription factor 2 (ATF2) isoforms in the human myometrium during pregnancy and labor: identification of a novel ATF2 species with potent transactivation properties."
Bailey J., Phillips R.J., Pollard A.J., Gilmore K., Robson S.C., Europe-Finner G.N.
J. Clin. Endocrinol. Metab. 87:1717-1728(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8).
Tissue: Myometrium.
[4]"Homo sapiens activating transcription factor 2 (ATF2) mRNA splice variant."
von Hippel A.C.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 5; 6 AND 7).
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Tissue: Brain.
[8]"A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain."
Kara C.J., Liou H.-C., Ivashkiv L.B., Glimcher L.H.
Mol. Cell. Biol. 10:1347-1357(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 211-505 (ISOFORMS 1/2).
[9]"Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade."
Enslen H., Tokumitsu H., Stork P.J., Davis R.J., Soderling T.R.
Proc. Natl. Acad. Sci. U.S.A. 93:10803-10808(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CAMK4.
[10]"Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6."
Enslen H., Raingeaud J., Davis R.J.
J. Biol. Chem. 273:1741-1748(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-69 AND THR-71.
[11]"Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity."
Fukushima A., Okuda A., Nishimoto M., Seki N., Hori T.A., Muramatsu M.
J. Biol. Chem. 273:25840-25849(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UTF1.
[12]"ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation."
Kawasaki H., Schiltz L., Chiu R., Itakura K., Taira K., Nakatani Y., Yokoyama K.K.
Nature 405:195-200(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF THR-69 AND THR-71.
[13]"Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38."
Ouwens D.M., de Ruiter N.D., van der Zon G.C., Carter A.P., Schouten J., van der Burgt C., Kooistra K., Bos J.L., Maassen J.A., van Dam H.
EMBO J. 21:3782-3793(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-69 AND THR-71.
[14]"Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK."
Sevilla A., Santos C.R., Vega F.M., Lazo P.A.
J. Biol. Chem. 279:27458-27465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-62 AND THR-73, SUBCELLULAR LOCATION.
[15]"ATM-dependent phosphorylation of ATF2 is required for the DNA damage response."
Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.
Mol. Cell 18:577-587(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NBN AND MRE11A, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-490 AND SER-498.
[16]"Multiple roles for acetylation in the interaction of p300 HAT with ATF-2."
Karanam B., Wang L., Wang D., Liu X., Marmorstein R., Cotter R., Cole P.A.
Biochemistry 46:8207-8216(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-357 AND LYS-374, IDENTIFICATION BY MASS SPECTROMETRY.
[17]"ATF2: a transcription factor that elicits oncogenic or tumor suppressor activities."
Bhoumik A., Ronai Z.
Cell Cycle 7:2341-2345(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[18]"Regulation of TIP60 by ATF2 modulates ATM activation."
Bhoumik A., Singha N., O'Connell M.J., Ronai Z.A.
J. Biol. Chem. 283:17605-17614(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CUL3 AND KAT5, SUBCELLULAR LOCATION.
[19]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Phosphorylation of activation transcription factor-2 at serine 121 by protein kinase c controls c-Jun-mediated activation of transcription."
Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.
J. Biol. Chem. 284:8567-8581(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-69; THR-71; SER-121; SER-340 AND SER-367, SUBCELLULAR LOCATION.
[23]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[24]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71; SER-112 AND THR-116, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in human corneal epithelial cells."
Wang L., Payton R., Dai W., Lu L.
J. Biol. Chem. 286:1951-1958(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-71, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-71.
[26]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71; SER-90 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria."
Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L., Ideker T., Ronai Z.A.
Cell 148:543-555(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HK1/VDAC1 COMPLEX, PHOSPHORYLATION AT THR-52.
[28]"Critical role of N-terminal end-localized nuclear export signal in regulation of activating transcription factor 2 (ATF2) subcellular localization and transcriptional activity."
Hsu C.C., Hu C.D.
J. Biol. Chem. 287:8621-8632(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, INTERACTION WITH XPO1, HETERODIMERIZATION WITH JUN.
[29]"ATF2-at the crossroad of nuclear and cytosolic functions."
Lau E., Ronai Z.A.
J. Cell Sci. 125:2815-2824(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[30]"Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain."
Nagadoi A., Nakazawa K., Uda H., Okuno K., Maekawa T., Ishii S., Nishimura Y.
J. Mol. Biol. 287:593-607(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 19-56.
[31]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-352.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15875 mRNA. Translation: CAA33886.1.
U16028 mRNA. Translation: AAB64017.1.
AY029364 mRNA. Translation: AAK55760.1.
DQ003037 mRNA. Translation: AAY17203.1. Different initiation.
DQ003038 mRNA. Translation: AAY17204.1.
DQ003041 mRNA. Translation: AAY17207.1. Different initiation.
DQ003044 mRNA. Translation: AAY17210.1.
DQ003047 mRNA. Translation: AAY17213.1.
DQ003049 mRNA. Translation: AAY17215.1.
AC131958 Genomic DNA. Translation: AAX88876.1.
AC074291 Genomic DNA. Translation: AAY15004.1.
AC007435 Genomic DNA. No translation available.
AC096649 Genomic DNA. No translation available.
CH471058 Genomic DNA. Translation: EAX11111.1.
CH471058 Genomic DNA. Translation: EAX11112.1.
CH471058 Genomic DNA. Translation: EAX11113.1.
BC026175 mRNA. Translation: AAH26175.1.
BC107698 mRNA. Translation: AAI07699.1.
BC130335 mRNA. Translation: AAI30336.1.
BC130337 mRNA. Translation: AAI30338.1.
M31630 mRNA. Translation: AAA35951.1.
CCDSCCDS2262.1. [P15336-1]
CCDS58737.1. [P15336-4]
CCDS58738.1. [P15336-5]
CCDS58739.1. [P15336-3]
PIRS05380.
RefSeqNP_001243019.1. NM_001256090.1. [P15336-1]
NP_001243020.1. NM_001256091.1. [P15336-5]
NP_001243021.1. NM_001256092.1. [P15336-4]
NP_001243022.1. NM_001256093.1.
NP_001243023.1. NM_001256094.1. [P15336-3]
NP_001871.2. NM_001880.3. [P15336-1]
UniGeneHs.592510.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BHINMR-A19-56[»]
1T2KX-ray3.00D354-414[»]
4H36X-ray3.00B48-55[»]
ProteinModelPortalP15336.
SMRP15336. Positions 19-56, 354-414.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107776. 190 interactions.
DIPDIP-632N.
IntActP15336. 183 interactions.
MINTMINT-1788434.
STRING9606.ENSP00000264110.

PTM databases

PhosphoSiteP15336.

Polymorphism databases

DMDM215274241.

Proteomic databases

MaxQBP15336.
PaxDbP15336.
PRIDEP15336.

Protocols and materials databases

DNASU1386.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264110; ENSP00000264110; ENSG00000115966. [P15336-1]
ENST00000345739; ENSP00000340576; ENSG00000115966. [P15336-4]
ENST00000392543; ENSP00000376326; ENSG00000115966. [P15336-6]
ENST00000392544; ENSP00000376327; ENSG00000115966. [P15336-1]
ENST00000409499; ENSP00000386282; ENSG00000115966. [P15336-8]
ENST00000409635; ENSP00000387093; ENSG00000115966. [P15336-4]
ENST00000409833; ENSP00000386526; ENSG00000115966. [P15336-3]
ENST00000426833; ENSP00000407911; ENSG00000115966. [P15336-5]
ENST00000487334; ENSP00000443513; ENSG00000115966. [P15336-7]
GeneID1386.
KEGGhsa:1386.
UCSCuc002ujl.4. human. [P15336-1]
uc002ujm.4. human.
uc002ujv.4. human. [P15336-2]
uc002ujy.2. human.

Organism-specific databases

CTD1386.
GeneCardsGC02M175937.
HGNCHGNC:784. ATF2.
HPACAB003769.
HPA022134.
MIM123811. gene.
neXtProtNX_P15336.
PharmGKBPA25084.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG306955.
HOGENOMHOG000220894.
HOVERGENHBG004300.
InParanoidP15336.
KOK04450.
OMATPIIRNK.
OrthoDBEOG741Z31.
PhylomeDBP15336.

Enzyme and pathway databases

ReactomeREACT_172623. Chromatin organization.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP15336.

Gene expression databases

ArrayExpressP15336.
BgeeP15336.
CleanExHS_ATF2.
GenevestigatorP15336.

Family and domain databases

Gene3D3.30.160.60. 1 hit.
InterProIPR004827. bZIP.
IPR016378. TF_cAMP-dep.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
PIRSFPIRSF003153. ATF2_CRE-BP1. 1 hit.
SMARTSM00338. BRLZ. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
PS50157. ZINC_FINGER_C2H2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATF2. human.
EvolutionaryTraceP15336.
GeneWikiActivating_transcription_factor_2.
GenomeRNAi1386.
NextBio35461711.
PROP15336.
SOURCESearch...

Entry information

Entry nameATF2_HUMAN
AccessionPrimary (citable) accession number: P15336
Secondary accession number(s): A1L3Z2 expand/collapse secondary AC list , A4D7U4, A4D7U5, A4D7V1, D3DPE9, G8JLM5, Q13000, Q3B7B7, Q4ZFU9, Q53RY2, Q8TAR1, Q96JT8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 163 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM