ATF2_HUMAN
ID ATF2_HUMAN Reviewed; 505 AA.
AC P15336; A1L3Z2; A4D7U4; A4D7U5; A4D7V1; D3DPE9; G8JLM5; Q13000; Q3B7B7;
AC Q4ZFU9; Q53RY2; Q8TAR1; Q96JT8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 4.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Cyclic AMP-dependent transcription factor ATF-2;
DE Short=cAMP-dependent transcription factor ATF-2;
DE AltName: Full=Activating transcription factor 2;
DE AltName: Full=Cyclic AMP-responsive element-binding protein 2;
DE Short=CREB-2;
DE Short=cAMP-responsive element-binding protein 2;
DE AltName: Full=HB16;
DE AltName: Full=cAMP response element-binding protein CRE-BP1;
GN Name=ATF2; Synonyms=CREB2, CREBP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=2529117; DOI=10.1002/j.1460-2075.1989.tb03610.x;
RA Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J.,
RA Yoshida M., Ishii S.;
RT "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP
RT response element in brain.";
RL EMBO J. 8:2023-2028(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=9058782;
RA Yang L., Lanier E.R., Kraig E.;
RT "Identification of a novel, spliced variant of CREB that is preferentially
RT expressed in the thymus.";
RL J. Immunol. 158:2522-2525(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8).
RC TISSUE=Myometrium;
RX PubMed=11932306; DOI=10.1210/jcem.87.4.8360;
RA Bailey J., Phillips R.J., Pollard A.J., Gilmore K., Robson S.C.,
RA Europe-Finner G.N.;
RT "Characterization and functional analysis of cAMP response element
RT modulator protein and activating transcription factor 2 (ATF2) isoforms in
RT the human myometrium during pregnancy and labor: identification of a novel
RT ATF2 species with potent transactivation properties.";
RL J. Clin. Endocrinol. Metab. 87:1717-1728(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 5; 6 AND 7).
RA von Hippel A.C.;
RT "Homo sapiens activating transcription factor 2 (ATF2) mRNA splice
RT variant.";
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 211-505 (ISOFORMS 1/2).
RX PubMed=2320002; DOI=10.1128/mcb.10.4.1347-1357.1990;
RA Kara C.J., Liou H.-C., Ivashkiv L.B., Glimcher L.H.;
RT "A cDNA for a human cyclic AMP response element-binding protein which is
RT distinct from CREB and expressed preferentially in brain.";
RL Mol. Cell. Biol. 10:1347-1357(1990).
RN [9]
RP PHOSPHORYLATION BY CAMK4.
RX PubMed=8855261; DOI=10.1073/pnas.93.20.10803;
RA Enslen H., Tokumitsu H., Stork P.J., Davis R.J., Soderling T.R.;
RT "Regulation of mitogen-activated protein kinases by a calcium/calmodulin-
RT dependent protein kinase cascade.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10803-10808(1996).
RN [10]
RP PHOSPHORYLATION AT THR-69 AND THR-71.
RX PubMed=9430721; DOI=10.1074/jbc.273.3.1741;
RA Enslen H., Raingeaud J., Davis R.J.;
RT "Selective activation of p38 mitogen-activated protein (MAP) kinase
RT isoforms by the MAP kinase kinases MKK3 and MKK6.";
RL J. Biol. Chem. 273:1741-1748(1998).
RN [11]
RP INTERACTION WITH UTF1.
RX PubMed=9748258; DOI=10.1074/jbc.273.40.25840;
RA Fukushima A., Okuda A., Nishimoto M., Seki N., Hori T.A., Muramatsu M.;
RT "Characterization of functional domains of an embryonic stem cell
RT coactivator UTF1 which are conserved and essential for potentiation of ATF-
RT 2 activity.";
RL J. Biol. Chem. 273:25840-25849(1998).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION, AND MUTAGENESIS OF THR-69
RP AND THR-71.
RX PubMed=10821277; DOI=10.1038/35012097;
RA Kawasaki H., Schiltz L., Chiu R., Itakura K., Taira K., Nakatani Y.,
RA Yokoyama K.K.;
RT "ATF-2 has intrinsic histone acetyltransferase activity which is modulated
RT by phosphorylation.";
RL Nature 405:195-200(2000).
RN [13]
RP PHOSPHORYLATION AT THR-69 AND THR-71.
RX PubMed=12110590; DOI=10.1093/emboj/cdf361;
RA Ouwens D.M., de Ruiter N.D., van der Zon G.C., Carter A.P., Schouten J.,
RA van der Burgt C., Kooistra K., Bos J.L., Maassen J.A., van Dam H.;
RT "Growth factors can activate ATF2 via a two-step mechanism: phosphorylation
RT of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-
RT p38.";
RL EMBO J. 21:3782-3793(2002).
RN [14]
RP PHOSPHORYLATION AT SER-62 AND THR-73, AND SUBCELLULAR LOCATION.
RX PubMed=15105425; DOI=10.1074/jbc.m401009200;
RA Sevilla A., Santos C.R., Vega F.M., Lazo P.A.;
RT "Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional
RT activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with
RT JNK.";
RL J. Biol. Chem. 279:27458-27465(2004).
RN [15]
RP FUNCTION, INTERACTION WITH NBN AND MRE11, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT SER-490 AND SER-498.
RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT response.";
RL Mol. Cell 18:577-587(2005).
RN [16]
RP ACETYLATION AT LYS-357 AND LYS-374, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17590016; DOI=10.1021/bi7000054;
RA Karanam B., Wang L., Wang D., Liu X., Marmorstein R., Cotter R., Cole P.A.;
RT "Multiple roles for acetylation in the interaction of p300 HAT with ATF-
RT 2.";
RL Biochemistry 46:8207-8216(2007).
RN [17]
RP REVIEW.
RX PubMed=18677098; DOI=10.4161/cc.6388;
RA Bhoumik A., Ronai Z.;
RT "ATF2: a transcription factor that elicits oncogenic or tumor suppressor
RT activities.";
RL Cell Cycle 7:2341-2345(2008).
RN [18]
RP FUNCTION, INTERACTION WITH CUL3 AND KAT5, AND SUBCELLULAR LOCATION.
RX PubMed=18397884; DOI=10.1074/jbc.m802030200;
RA Bhoumik A., Singha N., O'Connell M.J., Ronai Z.A.;
RT "Regulation of TIP60 by ATF2 modulates ATM activation.";
RL J. Biol. Chem. 283:17605-17614(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69 AND SER-112, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION AT THR-69; THR-71; SER-121; SER-340 AND SER-367, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19176525; DOI=10.1074/jbc.m808719200;
RA Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.;
RT "Phosphorylation of activation transcription factor-2 at serine 121 by
RT protein kinase c controls c-Jun-mediated activation of transcription.";
RL J. Biol. Chem. 284:8567-8581(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71 AND SER-112, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71; SER-112 AND
RP THR-116, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP PHOSPHORYLATION AT THR-71, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-71.
RX PubMed=21098032; DOI=10.1074/jbc.m110.166009;
RA Wang L., Payton R., Dai W., Lu L.;
RT "Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in
RT human corneal epithelial cells.";
RL J. Biol. Chem. 286:1951-1958(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71; SER-90 AND
RP SER-112, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HK1/VDAC1 COMPLEX, AND
RP PHOSPHORYLATION AT THR-52.
RX PubMed=22304920; DOI=10.1016/j.cell.2012.01.016;
RA Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L., Ideker T.,
RA Ronai Z.A.;
RT "PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while
RT blocking its apoptotic function at mitochondria.";
RL Cell 148:543-555(2012).
RN [28]
RP SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, INTERACTION WITH XPO1, AND
RP HETERODIMERIZATION WITH JUN.
RX PubMed=22275354; DOI=10.1074/jbc.m111.294272;
RA Hsu C.C., Hu C.D.;
RT "Critical role of N-terminal end-localized nuclear export signal in
RT regulation of activating transcription factor 2 (ATF2) subcellular
RT localization and transcriptional activity.";
RL J. Biol. Chem. 287:8621-8632(2012).
RN [29]
RP REVIEW.
RX PubMed=22685333; DOI=10.1242/jcs.095000;
RA Lau E., Ronai Z.A.;
RT "ATF2-at the crossroad of nuclear and cytosolic functions.";
RL J. Cell Sci. 125:2815-2824(2012).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; THR-69; THR-71; SER-112
RP AND SER-136, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-328; SER-442 AND
RP SER-446, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [32]
RP STRUCTURE BY NMR OF 19-56.
RX PubMed=10092462; DOI=10.1006/jmbi.1999.2620;
RA Nagadoi A., Nakazawa K., Uda H., Okuno K., Maekawa T., Ishii S.,
RA Nishimura Y.;
RT "Solution structure of the transactivation domain of ATF-2 comprising a
RT zinc finger-like subdomain and a flexible subdomain.";
RL J. Mol. Biol. 287:593-607(1999).
RN [33]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-352.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Transcriptional activator which regulates the transcription
CC of various genes, including those involved in anti-apoptosis, cell
CC growth, and DNA damage response. Dependent on its binding partner,
CC binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-
CC 3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-
CC 3'). In the nucleus, contributes to global transcription and the DNA
CC damage response, in addition to specific transcriptional activities
CC that are related to cell development, proliferation and death. In the
CC cytoplasm, interacts with and perturbs HK1- and VDAC1-containing
CC complexes at the mitochondrial outer membrane, thereby impairing
CC mitochondrial membrane potential, inducing mitochondrial leakage and
CC promoting cell death. The phosphorylated form (mediated by ATM) plays a
CC role in the DNA damage response and is involved in the ionizing
CC radiation (IR)-induced S phase checkpoint control and in the
CC recruitment of the MRN complex into the IR-induced foci (IRIF).
CC Exhibits histone acetyltransferase (HAT) activity which specifically
CC acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert
CC with CUL3 and RBX1, promotes the degradation of KAT5 thereby
CC attenuating its ability to acetylate and activate ATM. Can elicit
CC oncogenic or tumor suppressor activities depending on the tissue or
CC cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964,
CC ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}.
CC -!- SUBUNIT: Binds DNA as a dimer and can form a homodimer in the absence
CC of DNA. Can form a heterodimer with JUN. Heterodimerization is
CC essential for its transcriptional activity. Interacts with SMAD3 and
CC SMAD4. Binds through its N-terminal region to UTF1 which acts as a
CC coactivator of ATF2 transcriptional activity. Interacts with the
CC HK1/VDAC1 complex. Interacts with NBN, MRE11, XPO1, KAT5 and CUL3.
CC {ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884,
CC ECO:0000269|PubMed:22275354, ECO:0000269|PubMed:22304920,
CC ECO:0000269|PubMed:9748258}.
CC -!- INTERACTION:
CC P15336; P15336: ATF2; NbExp=2; IntAct=EBI-1170906, EBI-1170906;
CC P15336; P18847: ATF3; NbExp=5; IntAct=EBI-1170906, EBI-712767;
CC P15336; P18848: ATF4; NbExp=2; IntAct=EBI-1170906, EBI-492498;
CC P15336; O14867: BACH1; NbExp=2; IntAct=EBI-1170906, EBI-1263541;
CC P15336; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-1170906, EBI-11524452;
CC P15336; Q16520: BATF; NbExp=2; IntAct=EBI-1170906, EBI-749503;
CC P15336; Q9NR55: BATF3; NbExp=3; IntAct=EBI-1170906, EBI-10312707;
CC P15336; P53567: CEBPG; NbExp=2; IntAct=EBI-1170906, EBI-740209;
CC P15336; Q7L2Z9: CENPQ; NbExp=3; IntAct=EBI-1170906, EBI-2350265;
CC P15336; Q99966: CITED1; NbExp=2; IntAct=EBI-1170906, EBI-2624951;
CC P15336; P35638: DDIT3; NbExp=2; IntAct=EBI-1170906, EBI-742651;
CC P15336; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-1170906, EBI-371922;
CC P15336; P01100: FOS; NbExp=13; IntAct=EBI-1170906, EBI-852851;
CC P15336; Q6FG41: FOS; NbExp=3; IntAct=EBI-1170906, EBI-10198738;
CC P15336; P53539: FOSB; NbExp=3; IntAct=EBI-1170906, EBI-2806743;
CC P15336; P15408: FOSL2; NbExp=6; IntAct=EBI-1170906, EBI-3893419;
CC P15336; P56524: HDAC4; NbExp=2; IntAct=EBI-1170906, EBI-308629;
CC P15336; P05412: JUN; NbExp=18; IntAct=EBI-1170906, EBI-852823;
CC P15336; P17275: JUNB; NbExp=3; IntAct=EBI-1170906, EBI-748062;
CC P15336; P17535: JUND; NbExp=3; IntAct=EBI-1170906, EBI-2682803;
CC P15336; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-1170906, EBI-2125614;
CC P15336; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-1170906, EBI-14069005;
CC P15336; Q68G74: LHX8; NbExp=3; IntAct=EBI-1170906, EBI-8474075;
CC P15336; P45984: MAPK9; NbExp=9; IntAct=EBI-1170906, EBI-713568;
CC P15336; O95644: NFATC1; NbExp=2; IntAct=EBI-1170906, EBI-6907210;
CC P15336; O75928-2: PIAS2; NbExp=3; IntAct=EBI-1170906, EBI-348567;
CC P15336; P78317: RNF4; NbExp=3; IntAct=EBI-1170906, EBI-2340927;
CC P15336; Q6IQ16: SPOPL; NbExp=3; IntAct=EBI-1170906, EBI-2822161;
CC P15336; Q15532: SS18; NbExp=2; IntAct=EBI-1170906, EBI-2560599;
CC P15336; P63165: SUMO1; NbExp=6; IntAct=EBI-1170906, EBI-80140;
CC P15336; A4PIW0: SYT-SSX2; NbExp=11; IntAct=EBI-1170906, EBI-6050533;
CC P15336; Q99986: VRK1; NbExp=5; IntAct=EBI-1170906, EBI-1769146;
CC P15336; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-1170906, EBI-524753;
CC P15336; P0C746: HBZ; Xeno; NbExp=3; IntAct=EBI-1170906, EBI-10890294;
CC P15336; Q9DGW5: MDV005; Xeno; NbExp=2; IntAct=EBI-1170906, EBI-10889526;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion outer membrane.
CC Note=Shuttles between the cytoplasm and the nucleus and
CC heterodimerization with JUN is essential for the nuclear localization.
CC Localization to the cytoplasm is observed under conditions of cellular
CC stress and in disease states. Localizes at the mitochondrial outer
CC membrane in response to genotoxic stress. Phosphorylation at Thr-52 is
CC required for its nuclear localization and negatively regulates its
CC mitochondrial localization. Co-localizes with the MRN complex in the
CC IR-induced foci (IRIF).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1;
CC IsoId=P15336-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15336-2; Sequence=VSP_000587, VSP_000588;
CC Name=3;
CC IsoId=P15336-3; Sequence=VSP_045161;
CC Name=4;
CC IsoId=P15336-4; Sequence=VSP_046959;
CC Name=5;
CC IsoId=P15336-5; Sequence=VSP_046960;
CC Name=6;
CC IsoId=P15336-6; Sequence=VSP_046960, VSP_047593;
CC Name=7;
CC IsoId=P15336-7; Sequence=VSP_046960, VSP_047594, VSP_047595;
CC Name=8; Synonyms=ATF2-small;
CC IsoId=P15336-8; Sequence=VSP_047593;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with more abundant
CC expression in the brain.
CC -!- DOMAIN: The nuclear export signal 1 (N-NES) negatively regulates its
CC nuclear localization and transcriptional activity.
CC -!- PTM: Phosphorylation of Thr-69 by MAPK14 and MAPK11, and at Thr-71 by
CC MAPK1/ERK2, MAPK3/ERK1, MAPK11, MAPK12 and MAPK14 in response to
CC external stimulus like insulin causes increased transcriptional
CC activity (PubMed:9430721, PubMed:12110590). Phosphorylated by PLK3
CC following hyperosmotic stress (PubMed:21098032). Also phosphorylated
CC and activated by JNK and CaMK4 (PubMed:8855261). ATM-mediated
CC phosphorylation at Ser-490 and Ser-498 stimulates its function in DNA
CC damage response (PubMed:15916964). Phosphorylation at Ser-62, Thr-73
CC and Ser-121 activates its transcriptional activity (PubMed:15105425).
CC Phosphorylation at Thr-69 or Thr-71 enhances acetylation of histones
CC H2B and H4 (PubMed:10821277). {ECO:0000269|PubMed:10821277,
CC ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:15105425,
CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:21098032,
CC ECO:0000269|PubMed:8855261, ECO:0000269|PubMed:9430721}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
CC -!- CAUTION: Appears to have histone acetyltransferase (HAT) activity,
CC specifically towards histones H2B and H4 in vitro (PubMed:10821277).
CC However, it is not clear if this activity is genuine or caused by
CC contamination with other histone acetyltransferases in the assay.
CC {ECO:0000269|PubMed:10821277, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY17203.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAY17207.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ATF2ID718ch2q31.html";
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DR EMBL; X15875; CAA33886.1; -; mRNA.
DR EMBL; U16028; AAB64017.1; -; mRNA.
DR EMBL; AY029364; AAK55760.1; -; mRNA.
DR EMBL; DQ003037; AAY17203.1; ALT_INIT; mRNA.
DR EMBL; DQ003038; AAY17204.1; -; mRNA.
DR EMBL; DQ003041; AAY17207.1; ALT_INIT; mRNA.
DR EMBL; DQ003044; AAY17210.1; -; mRNA.
DR EMBL; DQ003047; AAY17213.1; -; mRNA.
DR EMBL; DQ003049; AAY17215.1; -; mRNA.
DR EMBL; AC131958; AAX88876.1; -; Genomic_DNA.
DR EMBL; AC074291; AAY15004.1; -; Genomic_DNA.
DR EMBL; AC007435; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11111.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11112.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11113.1; -; Genomic_DNA.
DR EMBL; BC026175; AAH26175.1; -; mRNA.
DR EMBL; BC107698; AAI07699.1; -; mRNA.
DR EMBL; BC130335; AAI30336.1; -; mRNA.
DR EMBL; BC130337; AAI30338.1; -; mRNA.
DR EMBL; M31630; AAA35951.1; -; mRNA.
DR CCDS; CCDS2262.1; -. [P15336-1]
DR CCDS; CCDS58737.1; -. [P15336-4]
DR CCDS; CCDS58738.1; -. [P15336-5]
DR CCDS; CCDS58739.1; -. [P15336-3]
DR PIR; S05380; S05380.
DR RefSeq; NP_001243019.1; NM_001256090.1. [P15336-1]
DR RefSeq; NP_001243020.1; NM_001256091.1. [P15336-5]
DR RefSeq; NP_001243021.1; NM_001256092.1. [P15336-4]
DR RefSeq; NP_001243022.1; NM_001256093.1.
DR RefSeq; NP_001243023.1; NM_001256094.1. [P15336-3]
DR RefSeq; NP_001871.2; NM_001880.3. [P15336-1]
DR PDB; 1BHI; NMR; -; A=19-56.
DR PDB; 1T2K; X-ray; 3.00 A; D=354-414.
DR PDB; 4H36; X-ray; 3.00 A; B=48-55.
DR PDB; 6ZQS; X-ray; 1.95 A; B=83-102.
DR PDB; 6ZR5; X-ray; 2.70 A; C/D=20-58.
DR PDBsum; 1BHI; -.
DR PDBsum; 1T2K; -.
DR PDBsum; 4H36; -.
DR PDBsum; 6ZQS; -.
DR PDBsum; 6ZR5; -.
DR AlphaFoldDB; P15336; -.
DR BMRB; P15336; -.
DR SMR; P15336; -.
DR BioGRID; 107776; 237.
DR ComplexPortal; CPX-6406; bZIP transcription factor complex, ATF2-ATF2.
DR ComplexPortal; CPX-6407; bZIP transcription factor complex, ATF2-ATF3.
DR ComplexPortal; CPX-6408; bZIP transcription factor complex, ATF2-ATF4.
DR ComplexPortal; CPX-6409; bZIP transcription factor complex, ATF2-ATF7.
DR ComplexPortal; CPX-6412; bZIP transcription factor complex, ATF2-BACH1.
DR ComplexPortal; CPX-6413; bZIP transcription factor complex, ATF2-BATF.
DR ComplexPortal; CPX-6414; bZIP transcription factor complex, ATF2-BATF3.
DR ComplexPortal; CPX-6415; bZIP transcription factor complex, ATF2-DDIT3.
DR ComplexPortal; CPX-6416; bZIP transcription factor complex, ATF2-FOS.
DR ComplexPortal; CPX-6417; bZIP transcription factor complex, ATF2-FOSL1.
DR ComplexPortal; CPX-6418; bZIP transcription factor complex, ATF2-FOSL2.
DR ComplexPortal; CPX-6419; bZIP transcription factor complex, ATF2-JDP2.
DR ComplexPortal; CPX-6420; bZIP transcription factor complex, ATF2-JUN.
DR ComplexPortal; CPX-6421; bZIP transcription factor complex, ATF2-JUNB.
DR ComplexPortal; CPX-6422; bZIP transcription factor complex, ATF2-JUND.
DR CORUM; P15336; -.
DR DIP; DIP-632N; -.
DR ELM; P15336; -.
DR IntAct; P15336; 225.
DR MINT; P15336; -.
DR STRING; 9606.ENSP00000264110; -.
DR DrugBank; DB00852; Pseudoephedrine.
DR MoonProt; P15336; -.
DR GlyGen; P15336; 9 sites, 2 O-linked glycans (9 sites).
DR iPTMnet; P15336; -.
DR PhosphoSitePlus; P15336; -.
DR BioMuta; ATF2; -.
DR DMDM; 215274241; -.
DR EPD; P15336; -.
DR jPOST; P15336; -.
DR MassIVE; P15336; -.
DR MaxQB; P15336; -.
DR PaxDb; P15336; -.
DR PeptideAtlas; P15336; -.
DR PRIDE; P15336; -.
DR ProteomicsDB; 34276; -.
DR ProteomicsDB; 53131; -. [P15336-1]
DR ProteomicsDB; 53132; -. [P15336-2]
DR ProteomicsDB; 61652; -.
DR ProteomicsDB; 650; -.
DR ProteomicsDB; 651; -.
DR ProteomicsDB; 73911; -.
DR ProteomicsDB; 77009; -.
DR Antibodypedia; 3529; 2572 antibodies from 52 providers.
DR DNASU; 1386; -.
DR Ensembl; ENST00000264110.7; ENSP00000264110.2; ENSG00000115966.18. [P15336-1]
DR Ensembl; ENST00000345739.9; ENSP00000340576.5; ENSG00000115966.18. [P15336-4]
DR Ensembl; ENST00000392544.5; ENSP00000376327.1; ENSG00000115966.18. [P15336-1]
DR Ensembl; ENST00000409499.5; ENSP00000386282.1; ENSG00000115966.18. [P15336-8]
DR Ensembl; ENST00000409635.5; ENSP00000387093.1; ENSG00000115966.18. [P15336-4]
DR Ensembl; ENST00000409833.5; ENSP00000386526.1; ENSG00000115966.18. [P15336-3]
DR Ensembl; ENST00000426833.7; ENSP00000407911.3; ENSG00000115966.18. [P15336-5]
DR GeneID; 1386; -.
DR KEGG; hsa:1386; -.
DR MANE-Select; ENST00000264110.7; ENSP00000264110.2; NM_001880.4; NP_001871.2.
DR UCSC; uc002ujk.5; human. [P15336-1]
DR CTD; 1386; -.
DR DisGeNET; 1386; -.
DR GeneCards; ATF2; -.
DR HGNC; HGNC:784; ATF2.
DR HPA; ENSG00000115966; Low tissue specificity.
DR MIM; 123811; gene.
DR neXtProt; NX_P15336; -.
DR OpenTargets; ENSG00000115966; -.
DR PharmGKB; PA25084; -.
DR VEuPathDB; HostDB:ENSG00000115966; -.
DR eggNOG; KOG1414; Eukaryota.
DR GeneTree; ENSGT00940000156582; -.
DR HOGENOM; CLU_1980813_0_0_1; -.
DR InParanoid; P15336; -.
DR OMA; NDLWNMS; -.
DR OrthoDB; 978850at2759; -.
DR PhylomeDB; P15336; -.
DR PathwayCommons; P15336; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; P15336; -.
DR SIGNOR; P15336; -.
DR BioGRID-ORCS; 1386; 19 hits in 1110 CRISPR screens.
DR ChiTaRS; ATF2; human.
DR EvolutionaryTrace; P15336; -.
DR GeneWiki; Activating_transcription_factor_2; -.
DR GenomeRNAi; 1386; -.
DR Pharos; P15336; Tbio.
DR PRO; PR:P15336; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P15336; protein.
DR Bgee; ENSG00000115966; Expressed in endothelial cell and 210 other tissues.
DR ExpressionAtlas; P15336; baseline and differential.
DR Genevisible; P15336; HS.
DR GO; GO:0016602; C:CCAAT-binding factor complex; IEA:Ensembl.
DR GO; GO:0000785; C:chromatin; IDA:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:1902562; C:H4 histone acetyltransferase complex; IDA:ARUK-UCL.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0035497; F:cAMP response element binding; IDA:BHF-UCL.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IDA:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0044013; F:H2B histone acetyltransferase activity; IDA:ARUK-UCL.
DR GO; GO:0010485; F:H4 histone acetyltransferase activity; IDA:ARUK-UCL.
DR GO; GO:0004402; F:histone acetyltransferase activity; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043522; F:leucine zipper domain binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0021742; P:abducens nucleus development; IEA:Ensembl.
DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR GO; GO:0097186; P:amelogenesis; IEA:Ensembl.
DR GO; GO:1902742; P:apoptotic process involved in development; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0003360; P:brainstem development; IEA:Ensembl.
DR GO; GO:0044255; P:cellular lipid metabolic process; IEA:Ensembl.
DR GO; GO:0072740; P:cellular response to anisomycin; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; IDA:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0060245; P:detection of cell density; IEA:Ensembl.
DR GO; GO:0021754; P:facial nucleus development; IEA:Ensembl.
DR GO; GO:0003418; P:growth plate cartilage chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0003419; P:growth plate cartilage chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0097284; P:hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0043969; P:histone H2B acetylation; IDA:ARUK-UCL.
DR GO; GO:0043967; P:histone H4 acetylation; IDA:ARUK-UCL.
DR GO; GO:0021743; P:hypoglossal nucleus development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:1990144; P:intrinsic apoptotic signaling pathway in response to hypoxia; IEA:Ensembl.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0001865; P:NK T cell differentiation; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0038066; P:p38MAPK cascade; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0110024; P:positive regulation of cardiac muscle myoblast proliferation; IDA:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:1902110; P:positive regulation of mitochondrial membrane permeability involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IEA:Ensembl.
DR GO; GO:0032915; P:positive regulation of transforming growth factor beta2 production; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0009414; P:response to water deprivation; IEA:Ensembl.
DR GO; GO:0007033; P:vacuole organization; IEA:Ensembl.
DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl.
DR IDEAL; IID00441; -.
DR InterPro; IPR029836; ATF2.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR016378; TF_CRE-BP1-typ.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR19304:SF9; PTHR19304:SF9; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR PIRSF; PIRSF003153; ATF2_CRE-BP1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57667; SSF57667; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm;
KW DNA damage; DNA-binding; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..505
FT /note="Cyclic AMP-dependent transcription factor ATF-2"
FT /id="PRO_0000076577"
FT DOMAIN 352..415
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT ZN_FING 25..49
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 125..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 296..299
FT /note="Essential for its histone acetyltransferase
FT activity"
FT REGION 354..374
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 380..408
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 425..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1..7
FT /note="Nuclear export signal 1 (N-NES)"
FT MOTIF 405..414
FT /note="Nuclear export signal 2 (C-NES)"
FT COMPBIAS 300..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..472
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphothreonine; by PKC/PRKCH"
FT /evidence="ECO:0000269|PubMed:22304920"
FT MOD_RES 62
FT /note="Phosphoserine; by VRK1"
FT /evidence="ECO:0000269|PubMed:15105425,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 69
FT /note="Phosphothreonine; by MAPK11 and MAPK14"
FT /evidence="ECO:0000269|PubMed:12110590,
FT ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:9430721,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 71
FT /note="Phosphothreonine; by MAPK1, MAPK3, MAPK11, MAPK12,
FT MAPK14 and PLK3"
FT /evidence="ECO:0000269|PubMed:12110590,
FT ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21098032,
FT ECO:0000269|PubMed:9430721, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 73
FT /note="Phosphothreonine; by VRK1"
FT /evidence="ECO:0000269|PubMed:15105425"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 116
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 121
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000269|PubMed:19176525"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 340
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000269|PubMed:19176525"
FT MOD_RES 357
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17590016"
FT MOD_RES 367
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000269|PubMed:19176525"
FT MOD_RES 374
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17590016"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 490
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:15916964"
FT MOD_RES 498
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:15916964"
FT VAR_SEQ 1..176
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9058782"
FT /id="VSP_000587"
FT VAR_SEQ 1..66
FT /note="MKFKLHVNSARQYKDLWNMSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMT
FT LKFGPARNDSVIVA -> MYCAWMWP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046959"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 5, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_046960"
FT VAR_SEQ 34..394
FT /note="Missing (in isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11932306, ECO:0000303|Ref.4"
FT /id="VSP_047593"
FT VAR_SEQ 177..185
FT /note="TSSDSSVII -> MSTAYFQMM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9058782"
FT /id="VSP_000588"
FT VAR_SEQ 210..505
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045161"
FT VAR_SEQ 210..237
FT /note="PVPGPFPLLLHLPNGQTMPVAIPASITS -> SFDQSPWCLVFQESQVLPLP
FT NQYSQKQK (in isoform 7)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047594"
FT VAR_SEQ 238..505
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047595"
FT VARIANT 352
FT /note="D -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035999"
FT MUTAGEN 69
FT /note="T->A: Weak histone acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:10821277"
FT MUTAGEN 71
FT /note="T->A: Impairs phosphorylation by PLK3. Weak histone
FT acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:10821277,
FT ECO:0000269|PubMed:21098032"
FT MUTAGEN 121
FT /note="S->A: Reduced phosphorylation and repression of c-
FT Jun-mediated activation of transcription."
FT CONFLICT 209
FT /note="V -> L (in Ref. 2; AAB64017)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="N -> S (in Ref. 1; CAA33886 and 4; AAY17203/
FT AAY17207/AAY17215)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="R -> L (in Ref. 2; AAB64017)"
FT /evidence="ECO:0000305"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:1BHI"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:6ZR5"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:6ZR5"
FT TURN 51..55
FT /evidence="ECO:0007829|PDB:1BHI"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:6ZQS"
FT HELIX 355..412
FT /evidence="ECO:0007829|PDB:1T2K"
SQ SEQUENCE 505 AA; 54537 MW; 0190EEFAEC8891A7 CRC64;
MKFKLHVNSA RQYKDLWNMS DDKPFLCTAP GCGQRFTNED HLAVHKHKHE MTLKFGPARN
DSVIVADQTP TPTRFLKNCE EVGLFNELAS PFENEFKKAS EDDIKKMPLD LSPLATPIIR
SKIEEPSVVE TTHQDSPLPH PESTTSDEKE VPLAQTAQPT SAIVRPASLQ VPNVLLTSSD
SSVIIQQAVP SPTSSTVITQ APSSNRPIVP VPGPFPLLLH LPNGQTMPVA IPASITSSNV
HVPAAVPLVR PVTMVPSVPG IPGPSSPQPV QSEAKMRLKA ALTQQHPPVT NGDTVKGHGS
GLVRTQSEES RPQSLQQPAT STTETPASPA HTTPQTQSTS GRRRRAANED PDEKRRKFLE
RNRAAASRCR QKRKVWVQSL EKKAEDLSSL NGQLQSEVTL LRNEVAQLKQ LLLAHKDCPV
TAMQKKSGYH TADKDDSSED ISVPSSPHTE AIQHSSVSTS NGVSSTSKAE AVATSVLTQM
ADQSTEPALS QIVMAPSSQS QPSGS
