ATF5_MOUSE
ID ATF5_MOUSE Reviewed; 283 AA.
AC O70191; Q58E51; Q99NH6;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 161.
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-alpha/beta;
DE AltName: Full=BZIP protein ATF7;
DE AltName: Full=NAP1;
DE AltName: Full=NRIF3-associated protein;
DE AltName: Full=Transcription factor ATFx;
DE AltName: Full=Transcription factor-like protein ODA-10;
GN Name=Atf5; Synonyms=Atfx, Nap1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=12213205; DOI=10.1006/geno.2002.6838;
RA Hansen M.B., Mitchelmore C., Kjaerulff K.M., Rasmussen T.E., Pedersen K.M.,
RA Jensen N.A.;
RT "Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization,
RT and odorant sensory neuron localization.";
RL Genomics 80:344-350(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11986327; DOI=10.1074/jbc.m202833200;
RA Angata T., Kerr S.C., Greaves D.R., Varki N.M., Crocker P.R., Varki A.;
RT "Cloning and characterization of human Siglec-11. A recently evolved
RT signaling molecule that can interact with SHP-1 and SHP-2 and is expressed
RT by tissue macrophages, including brain microglia.";
RL J. Biol. Chem. 277:24466-24474(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Li D., Samuels H.H.;
RT "The NRIF3-associated protein NAP1.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver, and Mammary gland;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 67-283, DNA-BINDING, TISSUE SPECIFICITY, AND
RP INTERACTION WITH PTP4A1.
RC TISSUE=Adipocyte;
RX PubMed=11278933; DOI=10.1074/jbc.m011562200;
RA Peters C.S., Liang X., Li S., Kannan S., Peng Y., Taub R., Diamond R.H.;
RT "ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine
RT phosphatase.";
RL J. Biol. Chem. 276:13718-13726(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 200-283.
RX PubMed=1371974; DOI=10.1016/0014-5793(92)80094-w;
RA Nishizawa M., Nagata S.;
RT "cDNA clones encoding leucine-zipper proteins which interact with G-CSF
RT gene promoter element 1-binding protein.";
RL FEBS Lett. 299:36-38(1992).
RN [7]
RP INDUCTION, AND FUNCTION.
RX PubMed=12130540; DOI=10.1101/gad.992202;
RA Persengiev S.P., Devireddy L.R., Green M.R.;
RT "Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB
RT family of mammalian bZIP transcription factors.";
RL Genes Dev. 16:1806-1814(2002).
RN [8]
RP INDUCTION.
RX PubMed=21768648; DOI=10.1074/jbc.m111.258970;
RA Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A.,
RA Matsunaga N., Ohdo S.;
RT "cAMP-response element (CRE)-mediated transcription by activating
RT transcription factor-4 (ATF4) is essential for circadian expression of the
RT Period2 gene.";
RL J. Biol. Chem. 286:32416-32423(2011).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=22095825; DOI=10.1002/dneu.20979;
RA Lee H.Y., Angelastro J.M., Kenney A.M., Mason C.A., Greene L.A.;
RT "Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule
RT neuron progenitor cells.";
RL Dev. Neurobiol. 72:789-804(2012).
RN [10]
RP FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP AND INDUCTION BY RETINOIC ACID.
RX PubMed=23090999; DOI=10.1073/pnas.1210479109;
RA Wang S.Z., Ou J., Zhu L.J., Green M.R.;
RT "Transcription factor ATF5 is required for terminal differentiation and
RT survival of olfactory sensory neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:18589-18594(2012).
RN [11]
RP FUNCTION, INTERACTION WITH CEBPB AND EP300, ACETYLATION AT LYS-29, AND
RP MUTAGENESIS OF LYS-29.
RX PubMed=24216764; DOI=10.1128/mcb.00956-13;
RA Zhao Y., Zhang Y.D., Zhang Y.Y., Qian S.W., Zhang Z.C., Li S.F., Guo L.,
RA Liu Y., Wen B., Lei Q.Y., Tang Q.Q., Li X.;
RT "p300-dependent acetylation of activating transcription factor 5 enhances
RT C/EBPbeta transactivation of C/EBPalpha during 3T3-L1 differentiation.";
RL Mol. Cell. Biol. 34:315-324(2014).
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 Important regulator of the cerebral cortex formation, functions in
CC cerebral cortical neuroprogenitor cells to maintain proliferation and
CC to block differentiation into neurons. Must be down-regulated in order
CC for such cells to exit the cycle and differentiate. Participates in the
CC pathways by which SHH promotes cerebellar granule neuron progenitor
CC cells proliferation (PubMed:22095825). Critical for survival of mature
CC olfactory sensory neurons (OSN), directs expression of OSN-specific
CC genes (PubMed:23090999). May be involved in osteogenic differentiation.
CC Promotes cell proliferation and survival by inducing the expression of
CC EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE
CC sequences on target genes promoters, such as BCL2 and EGR1 (By
CC similarity). Plays an anti-apoptotic role through the transcriptional
CC regulation of BCL2, this function seems to be cell type-dependent (By
CC similarity) (PubMed:12130540). 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:Q6P788, ECO:0000250|UniProtKB:Q9Y2D1,
CC ECO:0000269|PubMed:12130540, ECO:0000269|PubMed:22095825,
CC ECO:0000269|PubMed:23090999}.
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
CC (PubMed:24216764). {ECO:0000250|UniProtKB:Q9Y2D1,
CC ECO:0000269|PubMed:11278933, ECO:0000269|PubMed:24216764}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2D1}. Nucleus
CC {ECO:0000269|PubMed:22095825}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q9Y2D1}.
CC Note=Actively transported to the centrosome and accumulated in the
CC pericentriolar material (PCM) during G1 to M phase via a microtubule-
CC dependent mechanism. During late telophase and cytokinesis,
CC translocates from the centrosome to the midbody.
CC {ECO:0000250|UniProtKB:Q9Y2D1}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and at lower levels in
CC heart, brain, lung, kidney, adipose tissue, and skeletal muscle.
CC Expressed in some immature and in all mature olfactory sensory neurons
CC (at protein level) (PubMed:23090999). {ECO:0000269|PubMed:11278933,
CC ECO:0000269|PubMed:12213205, ECO:0000269|PubMed:23090999}.
CC -!- DEVELOPMENTAL STAGE: Expressed in sensory neurons during embryonic
CC development of the olfactory epithelium and vomeronasal organ. From, at
CC least, 11.5 dpc through adulthood, expressed in the olfactory system.
CC At 14.5 dpc, highly expressed in the olfactory epithelia, vomeronasal
CC organ, the Grueneberg ganglion, the septal organ and the olfactory bulb
CC (PubMed:23090999). At 14.5 dpc, expressed within germinal regions in
CC the ventricular zone of the brain, the rhombic lip and the nascent
CC external granule layer (EGL). At 16.5 dpc expression at the EGL is more
CC intense and extensive. From P1 to P15, expressed in cerebellar granule
CC neuron progenitor cells (CGNPs) of the EGL (PubMed:22095825).
CC {ECO:0000269|PubMed:12213205, ECO:0000269|PubMed:22095825,
CC ECO:0000269|PubMed:23090999}.
CC -!- INDUCTION: Expressed in a circadian manner in the liver. Down-regulated
CC by pro-apoptotic stimuli such IL3-deprivation that induce LCN2
CC expression (PubMed:12130540). In neural stem cells the expression is
CC induced by retinoic acid (PubMed:23090999).
CC {ECO:0000269|PubMed:12130540, ECO:0000269|PubMed:21768648,
CC ECO:0000269|PubMed:23090999}.
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:24216764}.
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 -!- DISRUPTION PHENOTYPE: The majority of pups die within 48h after birth
CC even if there is no major phenotypic differences at birth. Mice reveal
CC a lack of milk in their stomach and show a dramatic loss of mature
CC olfactory sensory neurons. {ECO:0000269|PubMed:23090999}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; AF375475; AAK54640.1; -; mRNA.
DR EMBL; AF375476; AAK54641.1; -; mRNA.
DR EMBL; AF312938; AAG34160.1; -; mRNA.
DR EMBL; AF310624; AAL55820.1; -; mRNA.
DR EMBL; AY115107; AAM74470.1; -; Genomic_DNA.
DR EMBL; BC010195; AAH10195.1; -; mRNA.
DR EMBL; BC092068; AAH92068.1; -; mRNA.
DR EMBL; AY024362; AAK00584.1; -; mRNA.
DR EMBL; AB012276; BAA25313.1; -; mRNA.
DR CCDS; CCDS21215.1; -.
DR RefSeq; NP_109618.1; NM_030693.2.
DR AlphaFoldDB; O70191; -.
DR SMR; O70191; -.
DR BioGRID; 223346; 2.
DR IntAct; O70191; 1.
DR STRING; 10090.ENSMUSP00000047771; -.
DR iPTMnet; O70191; -.
DR PhosphoSitePlus; O70191; -.
DR PaxDb; O70191; -.
DR PRIDE; O70191; -.
DR Antibodypedia; 18799; 301 antibodies from 33 providers.
DR DNASU; 107503; -.
DR Ensembl; ENSMUST00000047356; ENSMUSP00000047771; ENSMUSG00000038539.
DR Ensembl; ENSMUST00000107893; ENSMUSP00000103525; ENSMUSG00000038539.
DR GeneID; 107503; -.
DR KEGG; mmu:107503; -.
DR UCSC; uc009gqu.2; mouse.
DR CTD; 22809; -.
DR MGI; MGI:2141857; Atf5.
DR VEuPathDB; HostDB:ENSMUSG00000038539; -.
DR eggNOG; KOG4571; Eukaryota.
DR GeneTree; ENSGT00530000063801; -.
DR HOGENOM; CLU_083640_0_0_1; -.
DR InParanoid; O70191; -.
DR OMA; KIPGHYE; -.
DR OrthoDB; 1524842at2759; -.
DR PhylomeDB; O70191; -.
DR TreeFam; TF316136; -.
DR BioGRID-ORCS; 107503; 1 hit in 74 CRISPR screens.
DR PRO; PR:O70191; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O70191; protein.
DR Bgee; ENSMUSG00000038539; Expressed in olfactory system and 241 other tissues.
DR ExpressionAtlas; O70191; baseline and differential.
DR Genevisible; O70191; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
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:MGI.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0021891; P:olfactory bulb interneuron development; IMP:MGI.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:MGI.
DR GO; GO:0021988; P:olfactory lobe development; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0046605; P:regulation of centrosome cycle; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
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..283
FT /note="Cyclic AMP-dependent transcription factor ATF-5"
FT /id="PRO_0000076587"
FT DOMAIN 209..272
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..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..218
FT /note="Interaction with PTP4A1"
FT /evidence="ECO:0000269|PubMed:11278933"
FT REGION 168..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..231
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 237..251
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 120..151
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..202
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..241
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:24216764"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2D1"
FT MUTAGEN 29
FT /note="K->Q: Enhances interaction with CEBPB."
FT /evidence="ECO:0000269|PubMed:24216764"
FT MUTAGEN 29
FT /note="K->R: Decreases acetylation levels and interaction
FT with CEBPB."
FT /evidence="ECO:0000269|PubMed:24216764"
FT CONFLICT 146
FT /note="P -> PLP (in Ref. 5; AAK00584)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 30331 MW; 01FA2D352F0590CC CRC64;
MSLLATLGLE LDRALLPASG LGWLVDYGKL PLAPAPLGPY EVLGGALEGG LPGGGEPLAG
DGFSDWMTER VDFTALLPLE APLPPGTLPP PSPAPPDLEA MASLLKKELE QMEDFFLDAP
LLPPPSPPPP PPPAAAPSLP LPLPLPTFDL PQPPTLDTLD LLAVYCRSEA GPGDSGLSTL
PVPQQPPPLA PLPSPARPAP YPSPASTRGD RKQKKRDQNK SAALRYRQRK RAEGEALEGE
CQGLEARNRE LRERAESVER EIQYVKDLLI EVYKARSQRT RST
