UniProtKB - P16951 (ATF2_MOUSE)
Cyclic AMP-dependent transcription factor ATF-2
Atf2
Functioni
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 (By similarity).
By similarityCaution
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 7 – 31 | C2H2-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- cAMP response element binding Source: MGI
- cAMP response element binding protein binding Source: MGI
- chromatin binding Source: MGI
- cis-regulatory region sequence-specific DNA binding Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor activity Source: MGI
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- H2B histone acetyltransferase activity Source: MGI
- H4 histone acetyltransferase activity Source: MGI
- identical protein binding Source: MGI
- leucine zipper domain binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- promoter-specific chromatin binding Source: MGI
- protein-containing complex binding Source: MGI
- protein heterodimerization activity Source: MGI
- protein homodimerization activity Source: MGI
- protein kinase binding Source: MGI
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: MGI
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: MGI
- sequence-specific DNA binding Source: CAFA
- sequence-specific double-stranded DNA binding Source: MGI
GO - Biological processi
- abducens nucleus development Source: MGI
- adipose tissue development Source: MGI
- amelogenesis Source: MGI
- apoptotic process Source: MGI
- apoptotic process involved in development Source: MGI
- BMP signaling pathway Source: MGI
- brainstem development Source: MGI
- cellular lipid metabolic process Source: MGI
- cellular response to anisomycin Source: MGI
- cellular response to DNA damage stimulus Source: CAFA
- cellular response to leucine starvation Source: MGI
- cellular response to oxidative stress Source: MGI
- cellular response to virus Source: MGI
- detection of cell density Source: MGI
- facial nucleus development Source: MGI
- fat cell differentiation Source: MGI
- gene expression Source: MGI
- growth plate cartilage chondrocyte differentiation Source: MGI
- growth plate cartilage chondrocyte proliferation Source: MGI
- heart development Source: MGI
- hematopoietic progenitor cell differentiation Source: MGI
- hepatocyte apoptotic process Source: MGI
- histone H2B acetylation Source: MGI
- histone H4 acetylation Source: MGI
- hypoglossal nucleus development Source: MGI
- intrinsic apoptotic signaling pathway in response to hypoxia Source: MGI
- in utero embryonic development Source: MGI
- JNK cascade Source: MGI
- liver development Source: MGI
- MAPK cascade Source: MGI
- mitotic intra-S DNA damage checkpoint signaling Source: UniProtKB
- motor neuron apoptotic process Source: MGI
- mRNA transcription by RNA polymerase II Source: MGI
- negative regulation of angiogenesis Source: MGI
- negative regulation of epithelial cell proliferation Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- neurofilament cytoskeleton organization Source: MGI
- NK T cell differentiation Source: MGI
- outflow tract morphogenesis Source: MGI
- p38MAPK cascade Source: MGI
- peptidyl-threonine phosphorylation Source: MGI
- positive regulation of cardiac muscle myoblast proliferation Source: MGI
- positive regulation of DNA-binding transcription factor activity Source: UniProtKB
- positive regulation of gene expression Source: MGI
- positive regulation of mitochondrial membrane permeability involved in apoptotic process Source: UniProtKB
- positive regulation of neuron apoptotic process Source: MGI
- positive regulation of protein phosphorylation Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: MGI
- positive regulation of transforming growth factor beta2 production Source: MGI
- protein import into nucleus Source: MGI
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: MGI
- response to organic cyclic compound Source: MGI
- response to osmotic stress Source: UniProtKB
- response to water deprivation Source: Ensembl
- vacuole organization Source: MGI
- white fat cell differentiation Source: MGI
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | DNA damage, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-3214847, HATs acetylate histones R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-9018519, Estrogen-dependent gene expression |
Protein family/group databases
MoonProti | P16951 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclic AMP-dependent transcription factor ATF-2Short name: cAMP-dependent transcription factor ATF-2 Alternative name(s): Activating transcription factor 2 MXBP protein cAMP response element-binding protein CRE-BP1 |
Gene namesi | Name:Atf2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109349, Atf2 |
VEuPathDBi | HostDB:ENSMUSG00000027104 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
Mitochondrion
- Mitochondrion outer membrane By similarity
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-34 is required for its nuclear localization and negatively regulates its mitochondrial localization. Colocalizes with the MRN complex in the IR-induced foci (IRIF) (By similarity).By similarity
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
Nucleus
- CCAAT-binding factor complex Source: MGI
- H4 histone acetyltransferase complex Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- chromatin Source: MGI
- cytoplasm Source: UniProtKB
- membrane Source: MGI
- site of double-strand break Source: CAFA
Keywords - Cellular componenti
Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076578 | 1 – 487 | Cyclic AMP-dependent transcription factor ATF-2Add BLAST | 487 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 34 | Phosphothreonine; by PKC/PRKCHBy similarity | 1 | |
Modified residuei | 44 | PhosphoserineCombined sources | 1 | |
Modified residuei | 51 | Phosphothreonine; by MAPK11 and MAPK14Combined sources | 1 | |
Modified residuei | 53 | Phosphothreonine; by MAPK1, MAPK3, MAPK11, MAPK12, MAPK14 and PLK3Combined sources | 1 | |
Modified residuei | 55 | Phosphothreonine; by VRK1By similarity | 1 | |
Modified residuei | 72 | PhosphoserineCombined sources | 1 | |
Modified residuei | 94 | PhosphoserineCombined sources | 1 | |
Modified residuei | 98 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 103 | Phosphoserine; by PKC/PRKCA and PKC/PRKCBBy similarity | 1 | |
Modified residuei | 118 | PhosphoserineBy similarity | 1 | |
Modified residuei | 310 | PhosphoserineBy similarity | 1 | |
Modified residuei | 322 | Phosphoserine; by PKC/PRKCA and PKC/PRKCBBy similarity | 1 | |
Modified residuei | 339 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 349 | Phosphoserine; by PKC/PRKCA and PKC/PRKCBBy similarity | 1 | |
Modified residuei | 356 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 424 | PhosphoserineBy similarity | 1 | |
Modified residuei | 428 | PhosphoserineBy similarity | 1 | |
Modified residuei | 472 | Phosphoserine; by ATMBy similarity | 1 | |
Modified residuei | 480 | Phosphoserine; by ATMBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
jPOSTi | P16951 |
MaxQBi | P16951 |
PaxDbi | P16951 |
PeptideAtlasi | P16951 |
PRIDEi | P16951 |
ProteomicsDBi | 265142 [P16951-1] 265143 [P16951-2] 265144 [P16951-3] |
PTM databases
iPTMneti | P16951 |
PhosphoSitePlusi | P16951 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000027104, Expressed in paraventricular nucleus of hypothalamus and 334 other tissues |
ExpressionAtlasi | P16951, baseline and differential |
Genevisiblei | P16951, MM |
Interactioni
Subunit structurei
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.
Interacts with the HK1/VDAC1 complex.
Interacts with NBN, MRE11, XPO1, KAT5 and CUL3 (By similarity). Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity.
By similarity1 PublicationGO - Molecular functioni
- cAMP response element binding protein binding Source: MGI
- identical protein binding Source: MGI
- leucine zipper domain binding Source: MGI
- protein heterodimerization activity Source: MGI
- protein homodimerization activity Source: MGI
- protein kinase binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198233, 15 interactors |
IntActi | P16951, 5 interactors |
MINTi | P16951 |
STRINGi | 10090.ENSMUSP00000107641 |
Miscellaneous databases
RNActi | P16951, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 334 – 397 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 106 – 137 | DisorderedSequence analysisAdd BLAST | 32 | |
Regioni | 241 – 355 | DisorderedSequence analysisAdd BLAST | 115 | |
Regioni | 278 – 281 | Essential for its histone acetyltransferase activityBy similarity | 4 | |
Regioni | 336 – 356 | Basic motifPROSITE-ProRule annotationAdd BLAST | 21 | |
Regioni | 362 – 390 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 29 | |
Regioni | 407 – 453 | DisorderedSequence analysisAdd BLAST | 47 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 387 – 396 | Nuclear export signalBy similarity | 10 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 282 – 324 | Polar residuesSequence analysisAdd BLAST | 43 | |
Compositional biasi | 325 – 348 | Basic and acidic residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 424 – 453 | Polar residuesSequence analysisAdd BLAST | 30 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 7 – 31 | C2H2-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG1414, Eukaryota |
GeneTreei | ENSGT00940000156582 |
HOGENOMi | CLU_021564_0_0_1 |
InParanoidi | P16951 |
OMAi | IGKCEEV |
PhylomeDBi | P16951 |
Family and domain databases
InterProi | View protein in InterPro IPR029836, ATF2 IPR004827, bZIP IPR016378, TF_CRE-BP1-typ IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR19304:SF9, PTHR19304:SF9, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
PIRSFi | PIRSF003153, ATF2_CRE-BP1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57667, SSF57667, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit PS00028, ZINC_FINGER_C2H2_1, 1 hit PS50157, ZINC_FINGER_C2H2_2, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSDDKPFLCT APGCGQRFTN EDHLAVHKHK HEMTLKFGPA RNDSVIVADQ
60 70 80 90 100
TPTPTRFLKN CEEVGLFNEL ASPFENEFKK ASEDDIKKMP LDLSPLATPI
110 120 130 140 150
IRSKIEEPSV VETTHQDSPL PHPESTTSDE KEVPLAQTAQ PTSAIVRPAS
160 170 180 190 200
LQVPNVLLTS SDSSVIIQQA VPSPTSSTVI TQAPSSNRPI VPVPGPFPLL
210 220 230 240 250
LHLPNGQTMP VAIPASITSS NVHVPAAVPL VRPVTMVPSV PGIPGPSSPQ
260 270 280 290 300
PVQSEAKMRL KAALTQQHPP VTNGDTVKGH GSGLVRTQSE ESRPQSLQQP
310 320 330 340 350
ATSTTETPAS PAHTTPQTQN TSGRRRRAAN EDPDEKRRKF LERNRAAASR
360 370 380 390 400
CRQKRKVWVQ SLEKKAEDLS SLNGQLQSEV TLLRNEVAQL KQLLLAHKDC
410 420 430 440 450
PVTAMQKKSG YHTADKDDSS EDLSVPSSPH TEAIQHSSVS TSNGVSSTSK
460 470 480
AEAVATSVLT QMADQSTEPA LSQIVMAPPS QAQPSGS
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3UXC3 | G3UXC3_MOUSE | Cyclic AMP-dependent transcription ... | Atf2 | 377 | Annotation score: | ||
F6Z2B2 | F6Z2B2_MOUSE | Cyclic AMP-dependent transcription ... | Atf2 | 212 | Annotation score: | ||
A2AQE9 | A2AQE9_MOUSE | Cyclic AMP-dependent transcription ... | Atf2 | 207 | Annotation score: | ||
A2AQF0 | A2AQF0_MOUSE | Cyclic AMP-dependent transcription ... | Atf2 | 228 | Annotation score: | ||
A2AQF1 | A2AQF1_MOUSE | Cyclic AMP-dependent transcription ... | Atf2 | 146 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 482 – 487 | AQPSGS → HSPQEVD in AAB21128 (PubMed:11471062).Curated | 6 | |
Sequence conflicti | 482 – 487 | AQPSGS → HSPQEVD in AAB21129 (PubMed:11471062).Curated | 6 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000589 | 1 – 48 | MSDDK…SVIVA → MHCPWVWP in isoform 3. CuratedAdd BLAST | 48 | |
Alternative sequenceiVSP_000590 | 132 – 229 | Missing in isoform 2. CuratedAdd BLAST | 98 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF483482 mRNA Translation: AAL90756.1 AF483483 mRNA Translation: AAL90757.1 S76657 mRNA Translation: AAB21128.1 Different initiation. S76659 mRNA Translation: AAB21129.1 Different initiation. S76655 mRNA Translation: AAB21127.1 M31629 mRNA Translation: AAA39780.1 |
CCDSi | CCDS16134.1 [P16951-1] CCDS16135.1 [P16951-3] CCDS71076.1 [P16951-2] |
PIRi | A42026 C42026 |
RefSeqi | NP_001020264.1, NM_001025093.2 [P16951-1] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF483482 mRNA Translation: AAL90756.1 AF483483 mRNA Translation: AAL90757.1 S76657 mRNA Translation: AAB21128.1 Different initiation. S76659 mRNA Translation: AAB21129.1 Different initiation. S76655 mRNA Translation: AAB21127.1 M31629 mRNA Translation: AAA39780.1 |
CCDSi | CCDS16134.1 [P16951-1] CCDS16135.1 [P16951-3] CCDS71076.1 [P16951-2] |
PIRi | A42026 C42026 |
RefSeqi | NP_001020264.1, NM_001025093.2 [P16951-1] |
3D structure databases
BMRBi | P16951 |
SMRi | P16951 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198233, 15 interactors |
IntActi | P16951, 5 interactors |
MINTi | P16951 |
STRINGi | 10090.ENSMUSP00000107641 |
Chemistry databases
ChEMBLi | CHEMBL2176797 |
Protein family/group databases
MoonProti | P16951 |
PTM databases
iPTMneti | P16951 |
PhosphoSitePlusi | P16951 |
Proteomic databases
jPOSTi | P16951 |
MaxQBi | P16951 |
PaxDbi | P16951 |
PeptideAtlasi | P16951 |
PRIDEi | P16951 |
ProteomicsDBi | 265142 [P16951-1] 265143 [P16951-2] 265144 [P16951-3] |
Protocols and materials databases
Antibodypediai | 3529, 2535 antibodies from 51 providers |
DNASUi | 11909 |
Genome annotation databases
Organism-specific databases
CTDi | 1386 |
MGIi | MGI:109349, Atf2 |
VEuPathDBi | HostDB:ENSMUSG00000027104 |
Phylogenomic databases
eggNOGi | KOG1414, Eukaryota |
GeneTreei | ENSGT00940000156582 |
HOGENOMi | CLU_021564_0_0_1 |
InParanoidi | P16951 |
OMAi | IGKCEEV |
PhylomeDBi | P16951 |
Enzyme and pathway databases
Reactomei | R-MMU-3214847, HATs acetylate histones R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-9018519, Estrogen-dependent gene expression |
Miscellaneous databases
BioGRID-ORCSi | 11909, 1 hit in 67 CRISPR screens |
ChiTaRSi | Atf2, mouse |
PROi | PR:P16951 |
RNActi | P16951, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000027104, Expressed in paraventricular nucleus of hypothalamus and 334 other tissues |
ExpressionAtlasi | P16951, baseline and differential |
Genevisiblei | P16951, MM |
Family and domain databases
InterProi | View protein in InterPro IPR029836, ATF2 IPR004827, bZIP IPR016378, TF_CRE-BP1-typ IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR19304:SF9, PTHR19304:SF9, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
PIRSFi | PIRSF003153, ATF2_CRE-BP1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57667, SSF57667, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit PS00028, ZINC_FINGER_C2H2_1, 1 hit PS50157, ZINC_FINGER_C2H2_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ATF2_MOUSE | |
Accessioni | P16951Primary (citable) accession number: P16951 Secondary accession number(s): Q64089, Q64090, Q64091 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | May 30, 2000 | |
Last modified: | February 23, 2022 | |
This is version 201 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families