P16951 · ATF2_MOUSE

  • Protein
    Cyclic AMP-dependent transcription factor ATF-2
  • Gene
    Atf2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 (By similarity).

Caution

Appears to have histone acetyltransferase (HAT) activity, specifically towards histones H2B and H4 in vitro (By similarity).
However, it is not clear if this activity is genuine or caused by contamination with other histone acetyltransferases in the assay

GO annotations

AspectTerm
Cellular ComponentCCAAT-binding factor complex
Cellular Componentcytoplasm
Cellular ComponentH4 histone acetyltransferase complex
Cellular Componentmembrane
Cellular Componentmitochondrial outer membrane
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentsite of double-strand break
Molecular FunctioncAMP response element binding
Molecular FunctioncAMP response element binding protein binding
Molecular Functionchromatin binding
Molecular FunctionDNA binding
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionhistone H2B acetyltransferase activity
Molecular Functionhistone H4 acetyltransferase activity
Molecular Functionleucine zipper domain binding
Molecular Functionmetal ion binding
Molecular Functionpromoter-specific chromatin binding
Molecular Functionprotein heterodimerization activity
Molecular Functionprotein homodimerization activity
Molecular Functionprotein kinase binding
Molecular Functionprotein-containing complex binding
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functionsequence-specific DNA binding
Biological Processabducens nucleus development
Biological Processadipose tissue development
Biological Processamelogenesis
Biological Processapoptotic process
Biological Processapoptotic process involved in development
Biological ProcessBMP signaling pathway
Biological Processbrainstem development
Biological Processcellular lipid metabolic process
Biological Processcellular response to anisomycin
Biological Processcellular response to leucine starvation
Biological Processcellular response to oxidative stress
Biological Processcellular response to virus
Biological Processdetection of cell density
Biological ProcessDNA damage response
Biological Processfacial nucleus development
Biological Processgene expression
Biological Processgrowth plate cartilage chondrocyte differentiation
Biological Processgrowth plate cartilage chondrocyte proliferation
Biological Processheart development
Biological Processhematopoietic progenitor cell differentiation
Biological Processhepatocyte apoptotic process
Biological Processhypoglossal nucleus development
Biological Processin utero embryonic development
Biological Processintrinsic apoptotic signaling pathway in response to hypoxia
Biological ProcessJNK cascade
Biological Processliver development
Biological ProcessMAPK cascade
Biological Processmitotic intra-S DNA damage checkpoint signaling
Biological Processmotor neuron apoptotic process
Biological ProcessmRNA transcription by RNA polymerase II
Biological Processnegative regulation of angiogenesis
Biological Processnegative regulation of epithelial cell proliferation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processneurofilament cytoskeleton organization
Biological ProcessNK T cell differentiation
Biological Processoutflow tract morphogenesis
Biological Processp38MAPK cascade
Biological Processpositive regulation of cardiac muscle myoblast proliferation
Biological Processpositive regulation of DNA-binding transcription factor activity
Biological Processpositive regulation of mitochondrial membrane permeability involved in apoptotic process
Biological Processpositive regulation of neuron apoptotic process
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of transforming growth factor beta2 production
Biological Processprotein import into nucleus
Biological Processregulation of DNA-templated transcription
Biological Processregulation of transcription by RNA polymerase II
Biological Processresponse to organic cyclic compound
Biological Processresponse to osmotic stress
Biological Processtranscription initiation-coupled chromatin remodeling
Biological Processvacuole organization
Biological Processwhite fat cell differentiation

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Cyclic AMP-dependent transcription factor ATF-2
  • Short names
    cAMP-dependent transcription factor ATF-2
  • Alternative names
    • Activating transcription factor 2
    • MXBP protein
    • cAMP response element-binding protein CRE-BP1

Gene names

    • Name
      Atf2

Organism names

  • Taxonomic identifier
  • Strains
    • ILS
    • ISS
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P16951
  • Secondary accessions
    • Q64089
    • Q64090
    • Q64091

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
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).

Keywords

Phenotypes & Variants

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 13 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000765781-487Cyclic AMP-dependent transcription factor ATF-2
Modified residue34Phosphothreonine; by PKC/PRKCH
Modified residue44Phosphoserine
Modified residue51Phosphothreonine; by MAPK11 and MAPK14
Modified residue53Phosphothreonine; by MAPK1, MAPK3, MAPK11, MAPK12, MAPK14 and PLK3
Modified residue55Phosphothreonine; by VRK1
Modified residue72Phosphoserine
Modified residue94Phosphoserine
Modified residue98Phosphothreonine
Modified residue103Phosphoserine; by PKC/PRKCA and PKC/PRKCB
Modified residue118Phosphoserine
Modified residue310Phosphoserine
Modified residue322Phosphoserine; by PKC/PRKCA and PKC/PRKCB
Modified residue339N6-acetyllysine
Modified residue349Phosphoserine; by PKC/PRKCA and PKC/PRKCB
Modified residue356N6-acetyllysine
Modified residue424Phosphoserine
Modified residue428Phosphoserine
Modified residue472Phosphoserine; by ATM
Modified residue480Phosphoserine; by ATM

Post-translational modification

Phosphorylation of Thr-51 by MAPK14 and MAPK11, and at Thr-53 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-472 and Ser-480 stimulates its function in DNA damage response. Phosphorylation at Ser-44, Thr-55 and Ser-103 activates its transcriptional activity. Phosphorylation at Thr-51 or Thr-53 enhances acetylation of histones H2B and H4.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

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

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for zinc finger, region, compositional bias, domain, motif.

TypeIDPosition(s)Description
Zinc finger7-31C2H2-type
Region106-137Disordered
Region241-355Disordered
Region278-281Essential for its histone acetyltransferase activity
Compositional bias282-324Polar residues
Compositional bias325-348Basic and acidic residues
Domain334-397bZIP
Region336-356Basic motif
Region362-390Leucine-zipper
Motif387-396Nuclear export signal
Region407-453Disordered
Compositional bias424-453Polar residues

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

P16951-1

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.

  • Length
    487
  • Mass (Da)
    52,298
  • Last updated
    2000-05-30 v2
  • Checksum
    F9CDEC3BC3119ACB
MSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARNDSVIVADQTPTPTRFLKNCEEVGLFNELASPFENEFKKASEDDIKKMPLDLSPLATPIIRSKIEEPSVVETTHQDSPLPHPESTTSDEKEVPLAQTAQPTSAIVRPASLQVPNVLLTSSDSSVIIQQAVPSPTSSTVITQAPSSNRPIVPVPGPFPLLLHLPNGQTMPVAIPASITSSNVHVPAAVPLVRPVTMVPSVPGIPGPSSPQPVQSEAKMRLKAALTQQHPPVTNGDTVKGHGSGLVRTQSEESRPQSLQQPATSTTETPASPAHTTPQTQNTSGRRRRAANEDPDEKRRKFLERNRAAASRCRQKRKVWVQSLEKKAEDLSSLNGQLQSEVTLLRNEVAQLKQLLLAHKDCPVTAMQKKSGYHTADKDDSSEDLSVPSSPHTEAIQHSSVSTSNGVSSTSKAEAVATSVLTQMADQSTEPALSQIVMAPPSQAQPSGS

P16951-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P16951-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-48: MSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARNDSVIVA → MHCPWVWP

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A2AQE9A2AQE9_MOUSEAtf2207
A2AQF0A2AQF0_MOUSEAtf2228
A2AQF1A2AQF1_MOUSEAtf2146
F6Z2B2F6Z2B2_MOUSEAtf2212
G3UXC3G3UXC3_MOUSEAtf2377

Sequence caution

The sequence AAB21128.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.
The sequence AAB21129.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0005891-48in isoform 3
Alternative sequenceVSP_000590132-229in isoform 2
Compositional bias282-324Polar residues
Compositional bias325-348Basic and acidic residues
Compositional bias424-453Polar residues
Sequence conflict482-487in Ref. 1; AAB21128/AAB21129

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF483482
EMBL· GenBank· DDBJ
AAL90756.1
EMBL· GenBank· DDBJ
mRNA
AF483483
EMBL· GenBank· DDBJ
AAL90757.1
EMBL· GenBank· DDBJ
mRNA
S76657
EMBL· GenBank· DDBJ
AAB21128.1
EMBL· GenBank· DDBJ
mRNA Different initiation
S76659
EMBL· GenBank· DDBJ
AAB21129.1
EMBL· GenBank· DDBJ
mRNA Different initiation
S76655
EMBL· GenBank· DDBJ
AAB21127.1
EMBL· GenBank· DDBJ
mRNA
M31629
EMBL· GenBank· DDBJ
AAA39780.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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