ATF5_RAT
ID ATF5_RAT Reviewed; 281 AA.
AC Q6P788; Q8CIT6;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 130.
DE RecName: Full=Cyclic AMP-dependent transcription factor ATF-5;
DE Short=cAMP-dependent transcription factor ATF-5;
DE AltName: Full=Activating transcription factor 5;
DE AltName: Full=Transcription factor ATFx;
GN Name=Atf5; Synonyms=Atfx;
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], DEVELOPMENTAL STAGE, INDUCTION, AND FUNCTION.
RC STRAIN=New England Deaconess Hospital;
RX PubMed=12805299; DOI=10.1523/jneurosci.23-11-04590.2003;
RA Angelastro J.M., Ignatova T.N., Kukekov V.G., Steindler D.A.,
RA Stengren G.B., Mendelsohn C., Greene L.A.;
RT "Regulated expression of ATF5 is required for the progression of neural
RT progenitor cells to neurons.";
RL J. Neurosci. 23:4590-4600(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [3]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=19531563; DOI=10.1158/1541-7786.mcr-08-0365;
RA Li G., Li W., Angelastro J.M., Greene L.A., Liu D.X.;
RT "Identification of a novel DNA binding site and a transcriptional target
RT for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer
RT cells.";
RL Mol. Cancer Res. 7:933-943(2009).
RN [4]
RP FUNCTION, AND INDUCTION BY PRO-APOPTOTIC STIMULI.
RX PubMed=21212266; DOI=10.1074/jbc.m110.207639;
RA Dluzen D., Li G., Tacelosky D., Moreau M., Liu D.X.;
RT "BCL-2 is a downstream target of ATF5 that mediates the prosurvival
RT function of ATF5 in a cell type-dependent manner.";
RL J. Biol. Chem. 286:7705-7713(2011).
RN [5]
RP FUNCTION, INTERACTION WITH EP300, ACETYLATION AT LYS-29, AND MUTAGENESIS OF
RP LYS-29.
RX PubMed=21791614; DOI=10.1128/mcb.05887-11;
RA Liu D.X., Qian D., Wang B., Yang J.M., Lu Z.;
RT "p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and
RT cell proliferation and survival.";
RL Mol. Cell. Biol. 31:3906-3916(2011).
CC -!- FUNCTION: Transcription factor that either stimulates or represses gene
CC transcription through binding of different DNA regulatory elements such
CC as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'),
CC ATF5-specific response element (ARE) (consensus: 5'-
CC C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element
CC (AARE), present in many viral and cellular promoters. Critically
CC involved, often in a cell type-dependent manner, in cell survival,
CC proliferation, and differentiation. Its transcriptional activity is
CC enhanced by CCND3 and slightly inhibited by CDK4 (By similarity)
CC (PubMed:19531563, PubMed:21212266). Important regulator of the cerebral
CC cortex formation, functions in cerebral cortical neuroprogenitor cells
CC to maintain proliferation and to block differentiation into neurons.
CC Must be down-regulated in order for such cells to exit the cycle and
CC differentiate (By similarity) (PubMed:12805299). Participates in the
CC pathways by which SHH promotes cerebellar granule neuron progenitor
CC cells proliferation. Critical for survival of mature olfactory sensory
CC neurons (OSN), directs expression of OSN-specific genes (By
CC similarity). May be involved in osteogenic differentiation. Promotes
CC cell proliferation and survival by inducing the expression of EGR1
CC sinergistically with ELK1. Once acetylated by EP300, binds to ARE
CC sequences on target genes promoters, such as BCL2 and EGR1 (By
CC similarity) (PubMed:21791614). Plays an anti-apoptotic role through the
CC transcriptional regulation of BCL2, this function seems to be cell
CC type-dependent (By similarity). Cooperates with NR1I3/CAR in the
CC transcriptional activation of CYP2B6 in liver. In hepatic cells,
CC represses CRE-dependent transcription and inhibits proliferation by
CC blocking at G2/M phase. May act as a negative regulator of IL1B
CC transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK
CC to activate the transactivation activity of C/EBP subfamily members.
CC Besides its function of transcription factor, acts as a cofactor of
CC CEBPB to activate CEBPA and promote adipocyte differentiation.
CC Regulates centrosome dynamics in a cell-cycle- and centriole-age-
CC dependent manner. Forms 9-foci symmetrical ring scaffold around the
CC mother centriole to control centrosome function and the interaction
CC between centrioles and pericentriolar material (By similarity).
CC {ECO:0000250|UniProtKB:O70191, ECO:0000250|UniProtKB:Q9Y2D1,
CC ECO:0000269|PubMed:12805299, ECO:0000269|PubMed:19531563,
CC ECO:0000269|PubMed:21212266, ECO:0000269|PubMed:21791614}.
CC -!- SUBUNIT: Binds DNA as a dimer. Interacts with PTP4A1/PRL-1 (By
CC similarity). Interacts with CCND3, but not with CCND1 or CCND2.
CC Interacts with HSPA1A or HSPA1B; the interaction protects ATF5 from
CC degradation via proteasome-dependent and caspase-dependent processes.
CC Interacts (via C-terminal region) with NPM1 (via C-terminal region);
CC the interaction leads to loss of association between HSPA1A or HSPA1B
CC and ATF5 and promotes ATF5 degradation via proteasome-dependent and
CC caspase-dependent processes. Interacts with NLK; the interaction
CC stabilizes ATF5 at the protein level in a kinase-independent manner.
CC Interacts with alpha-tubulin, gamma-tubulin members TUBGCP2 and
CC TUBGCP4, PCNT; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite
CC unites the mother centriole and the pericentriolar material (PCM) in
CC the centrosome (By similarity). Interacts with CEBPB and EP300; EP300
CC is required for ATF5 and CEBPB interaction and DNA binding (By
CC similarity) (PubMed:21791614). {ECO:0000250|UniProtKB:O70191,
CC ECO:0000250|UniProtKB:Q9Y2D1, ECO:0000269|PubMed:21791614}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2D1}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y2D1, ECO:0000255|PROSITE-ProRule:PRU00978}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q9Y2D1}. Note=Actively transported to the
CC centrosome and accumulated in the pericentriolar material (PCM) during
CC G1 to M phase via a microtubule-dependent mechanism. During late
CC telophase and cytokinesis, translocates from the centrosome to the
CC midbody. {ECO:0000250|UniProtKB:Q9Y2D1}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic nasal epithelium, dorsal
CC root, trigeminal ganglia, brain and liver. Within the brain, expression
CC is highest in the ventricular zone and decreased in structures
CC containing migrating and postmitotic neurons (at protein level).
CC {ECO:0000269|PubMed:12805299}.
CC -!- INDUCTION: Down-regulated during neuronal differentiation. Down-
CC regulated by pro-apoptotic stimuli (PubMed:21212266).
CC {ECO:0000269|PubMed:12805299, ECO:0000269|PubMed:21212266}.
CC -!- PTM: Ubiquitinated by CDC34 and UBE2B in order to be degraded by the
CC proteasome. {ECO:0000250}.
CC -!- PTM: Acetylated at Lys-29 by EP300, the acetylation enhances the
CC interaction with CEBPB, DNA-binding and transactivation activity.
CC {ECO:0000269|PubMed:21791614}.
CC -!- PTM: Ubiquitinated by CDC34 and UBE2B in order to be degraded by the
CC proteasome. Cisplatin inhibits ubiquitination and proteasome-mediated
CC degradation by inhibiting the interaction with CDC34. Ubiquitination
CC and degradation by the proteasome are inhibited by NLK in a kinase-
CC independent manner. {ECO:0000250|UniProtKB:Q9Y2D1}.
CC -!- PTM: Phosphorylated by NLK, probably at Ser-92 and Ser-126.
CC {ECO:0000250|UniProtKB:Q9Y2D1}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY123225; AAM92263.1; -; mRNA.
DR EMBL; BC061786; AAH61786.1; -; mRNA.
DR RefSeq; NP_758839.3; NM_172336.3.
DR RefSeq; XP_006229042.1; XM_006228980.2.
DR RefSeq; XP_017444334.1; XM_017588845.1.
DR AlphaFoldDB; Q6P788; -.
DR SMR; Q6P788; -.
DR BioGRID; 251873; 1.
DR STRING; 10116.ENSRNOP00000027260; -.
DR iPTMnet; Q6P788; -.
DR PhosphoSitePlus; Q6P788; -.
DR PaxDb; Q6P788; -.
DR GeneID; 282840; -.
DR KEGG; rno:282840; -.
DR UCSC; RGD:628902; rat.
DR CTD; 22809; -.
DR RGD; 628902; Atf5.
DR eggNOG; KOG4571; Eukaryota.
DR InParanoid; Q6P788; -.
DR OrthoDB; 1524842at2759; -.
DR PhylomeDB; Q6P788; -.
DR TreeFam; TF316136; -.
DR PRO; PR:Q6P788; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; ISO:RGD.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IMP:RGD.
DR GO; GO:1902750; P:negative regulation of cell cycle G2/M phase transition; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IDA:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0021891; P:olfactory bulb interneuron development; ISO:RGD.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; ISO:RGD.
DR GO; GO:0021988; P:olfactory lobe development; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0046605; P:regulation of centrosome cycle; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; 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; ISO:RGD.
DR InterPro; IPR029855; ATF5.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR PANTHER; PTHR13044:SF3; PTHR13044:SF3; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Cytoplasm; Cytoskeleton; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..281
FT /note="Cyclic AMP-dependent transcription factor ATF-5"
FT /id="PRO_0000076588"
FT DOMAIN 207..270
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..21
FT /note="Required for protein stabilization induced by IL1B"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2D1"
FT REGION 118..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..216
FT /note="Interaction with PTP4A1"
FT /evidence="ECO:0000250|UniProtKB:O70191"
FT REGION 166..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..229
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 235..249
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 120..149
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 179..198
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000269|PubMed:21791614"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2D1"
FT MUTAGEN 29
FT /note="K->R: Not acetylated by EP300."
FT /evidence="ECO:0000269|PubMed:21791614"
FT CONFLICT 193
FT /note="L -> P (in Ref. 1; AAM92263)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 281 AA; 30205 MW; FBBF68FB44F9C601 CRC64;
MSLLATLGLE LDRALLPASG LGWLVDYGKL PLAPAPLGPY EVLGGALEGG LPGGGEPLAG
DGFSDWMTER VDFTALLPLE APLPPGTLPP PSPAPPDLEA MASLLKKELE QMEDFFLDAP
LLPPPSPPPP PPPAPSLPLP LPLPTFDLPQ PPTLDTLDLL AVYCRSEAGP GDSGLTTLPV
PQQPPPLAPL PSLSRPAPYP SPASTRGDRK QKKRDQNKSA ALRYRQRKRA EGEALEGECQ
GLEARNRELR ERAESVEREI QYVKDLLIEV YKARSQRTRS A
