ATF2_RAT
ID ATF2_RAT Reviewed; 487 AA.
AC Q00969; Q62870;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 171.
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=cAMP response element-binding protein CRE-BP1;
GN Name=Atf2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=1714459; DOI=10.1016/s0021-9258(18)98648-5;
RA Kageyama R., Sasai Y., Nakanishi S.;
RT "Molecular characterization of transcription factors that bind to the cAMP
RT responsive region of the substance P precursor gene. cDNA cloning of a
RT novel C/EBP-related factor.";
RL J. Biol. Chem. 266:15525-15531(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Muramatsu S.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-51; THR-53 AND SER-94, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. In concert with CUL3 and RBX1,
CC promotes the degradation of KAT5 thereby attenuating its ability to
CC acetylate and activate ATM. Can elicit oncogenic or tumor suppressor
CC activities depending on the tissue or cell type (By similarity).
CC {ECO:0000250}.
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 (By similarity). Interacts
CC with the HK1/VDAC1 complex. Interacts with NBN, MRE11, XPO1, KAT5 and
CC CUL3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Mitochondrion
CC outer membrane {ECO:0000250}. Note=Shuttles between the cytoplasm and
CC the nucleus and heterodimerization with JUN is essential for the
CC nuclear localization. Localization to the cytoplasm is observed under
CC conditions of cellular stress and in disease states. Localizes at the
CC mitochondrial outer membrane in response to genotoxic stress.
CC Phosphorylation at Thr-34 is required for its nuclear localization and
CC negatively regulates its mitochondrial localization. Colocalizes with
CC the MRN complex in the IR-induced foci (IRIF) (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q00969-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q00969-2; Sequence=VSP_000591;
CC -!- PTM: Phosphorylation of Thr-51 by MAPK14 and MAPK11, and at Thr-53 by
CC MAPK1/ERK2, MAPK3/ERK1, MAPK11, MAPK12 and MAPK14 in response to
CC external stimulus like insulin causes increased transcriptional
CC activity. Phosphorylated by PLK3 following hyperosmotic stress. Also
CC phosphorylated and activated by JNK and CaMK4. ATM-mediated
CC phosphorylation at Ser-472 and Ser-480 stimulates its function in DNA
CC damage response. Phosphorylation at Ser-44, Thr-55 and Ser-103
CC activates its transcriptional activity. Phosphorylation at Thr-51 or
CC Thr-53 enhances acetylation of histones H2B and H4.
CC {ECO:0000250|UniProtKB:P15336}.
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 (By similarity).
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:0000250|UniProtKB:P15336, ECO:0000305}.
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DR EMBL; M65148; AAA42013.1; -; mRNA.
DR EMBL; U38938; AAA93263.1; -; mRNA.
DR PIR; A39429; A39429.
DR RefSeq; NP_112280.1; NM_031018.1. [Q00969-1]
DR AlphaFoldDB; Q00969; -.
DR BMRB; Q00969; -.
DR SMR; Q00969; -.
DR BioGRID; 249547; 3.
DR CORUM; Q00969; -.
DR STRING; 10116.ENSRNOP00000002174; -.
DR iPTMnet; Q00969; -.
DR PhosphoSitePlus; Q00969; -.
DR PaxDb; Q00969; -.
DR PRIDE; Q00969; -.
DR Ensembl; ENSRNOT00000050513; ENSRNOP00000046001; ENSRNOG00000001597. [Q00969-2]
DR GeneID; 81647; -.
DR KEGG; rno:81647; -.
DR UCSC; RGD:621862; rat. [Q00969-1]
DR CTD; 1386; -.
DR RGD; 621862; Atf2.
DR VEuPathDB; HostDB:ENSRNOG00000001597; -.
DR eggNOG; KOG1414; Eukaryota.
DR GeneTree; ENSGT00940000156582; -.
DR HOGENOM; CLU_021564_0_0_1; -.
DR InParanoid; Q00969; -.
DR OMA; NDLWNMS; -.
DR OrthoDB; 978850at2759; -.
DR PhylomeDB; Q00969; -.
DR Reactome; R-RNO-3214847; HATs acetylate histones.
DR Reactome; R-RNO-450341; Activation of the AP-1 family of transcription factors.
DR PRO; PR:Q00969; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000001597; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q00969; RN.
DR GO; GO:0016602; C:CCAAT-binding factor complex; IDA:MGI.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:1902562; C:H4 histone acetyltransferase complex; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0035497; F:cAMP response element binding; IDA:RGD.
DR GO; GO:0008140; F:cAMP response element binding protein binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0044013; F:H2B histone acetyltransferase activity; ISO:RGD.
DR GO; GO:0010485; F:H4 histone acetyltransferase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0043522; F:leucine zipper domain binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0021742; P:abducens nucleus development; ISO:RGD.
DR GO; GO:0060612; P:adipose tissue development; ISO:RGD.
DR GO; GO:0097186; P:amelogenesis; IDA:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:1902742; P:apoptotic process involved in development; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0003360; P:brainstem development; ISO:RGD.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR GO; GO:0072740; P:cellular response to anisomycin; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; ISO:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0060245; P:detection of cell density; ISO:RGD.
DR GO; GO:0021754; P:facial nucleus development; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0003418; P:growth plate cartilage chondrocyte differentiation; ISO:RGD.
DR GO; GO:0003419; P:growth plate cartilage chondrocyte proliferation; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:RGD.
DR GO; GO:0043969; P:histone H2B acetylation; ISO:RGD.
DR GO; GO:0043967; P:histone H4 acetylation; ISO:RGD.
DR GO; GO:0021743; P:hypoglossal nucleus development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:1990144; P:intrinsic apoptotic signaling pathway in response to hypoxia; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0097049; P:motor neuron apoptotic process; ISO:RGD.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; ISO:RGD.
DR GO; GO:0001865; P:NK T cell differentiation; ISO:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0038066; P:p38MAPK cascade; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0110024; P:positive regulation of cardiac muscle myoblast proliferation; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1902110; P:positive regulation of mitochondrial membrane permeability involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISO:RGD.
DR GO; GO:0032915; P:positive regulation of transforming growth factor beta2 production; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:RGD.
DR GO; GO:0006970; P:response to osmotic stress; ISS:UniProtKB.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0007033; P:vacuole organization; ISO:RGD.
DR GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
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 Acetylation; Activator; Alternative splicing; Cytoplasm; DNA damage;
KW DNA-binding; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..487
FT /note="Cyclic AMP-dependent transcription factor ATF-2"
FT /id="PRO_0000076579"
FT DOMAIN 334..397
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT ZN_FING 7..31
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 107..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..281
FT /note="Essential for its histone acetyltransferase
FT activity"
FT /evidence="ECO:0000250"
FT REGION 336..356
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 362..390
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 407..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 387..396
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 288..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..348
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphothreonine; by PKC/PRKCH"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 44
FT /note="Phosphoserine; by VRK1"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 51
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 53
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 55
FT /note="Phosphothreonine; by VRK1"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 98
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 103
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 322
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 339
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 349
FT /note="Phosphoserine; by PKC/PRKCA and PKC/PRKCB"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 356
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 472
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT MOD_RES 480
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:P15336"
FT VAR_SEQ 132..229
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1714459"
FT /id="VSP_000591"
SQ SEQUENCE 487 AA; 52287 MW; 4ED95B106DF5F9EE CRC64;
MSDDKPFLCT APGCGQRFTN EDHLAVHKHK HEMTLKFGPA RNDSVIVADQ TPTPTRFLKN
CEEVGLFNEL ASPFENEFKK ASEDDIKKMP LDLSPLATPI IRSKIEEPSV VETTHQDSPL
PHPESTTNDE KEIPLAQTAQ PTSAIVRPAS LQVPNVLLTS SDSSVIIQQA VPSPTSSTVI
TQAPSSNRPI VPVPGPFPLL LHLPNGQTMP VAIPASITSS NVHVPAAVPL VRPVTMVPSV
PGIPGPSSPQ PVQSEAKMRL KAALTQQHPP VTNGDTVKGH GSGLVRAQSE ESRPQSLQQP
ATSTTETPAS PAHTTPQTQN TSGRRRRAAN EDPDEKRRKF LERNRAAASR CRQKRKVWVQ
SLEKKAEDLS SLNGQLQSEV TLLRNEVAQL KQLLLAHKDC PVTAMQKKSG YHTADKDDSS
EDLSVPSSPH TEAIQHSSVS TSNGVSSTSK TEAGATSVLT QMADQSTEPA LSQIVMAPSS
QAQPSGS
