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Protein

Cyclic AMP-dependent transcription factor ATF-5

Gene

Atf5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), ATF5-specific response element (ARE) (consensus: 5'-C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4 (By similarity). Important regulator of the cerebral cortex formation, functions in cerebral cortical neuroprogenitor cells to maintain proliferation and to block differentiation into neurons. Must be down-regulated in order for such cells to exit the cycle and differentiate. Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation (PubMed:22095825). Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes (PubMed:23090999). May be involved in osteogenic differentiation. Promotes cell proliferation and survival by inducing the expression of EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE sequences on target genes promoters, such as BCL2 and EGR1 (By similarity). Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent (By similarity) (PubMed:12130540). Cooperates with NR1I3/CAR in the transcritpional activation of CYP2B6 in liver. In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2/M phase. May act as a negative regulator of IL1B transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C/EBP subfamily members. Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation. Regulates centrosome dynamics in a cell-cycle- and centriole-age-dependent manner. Forms 9-foci symmetrical ring scaffold around the mother centriole to control centrosome function and the interaction between centrioles and pericentriolar material (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • multicellular organism growth Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of astrocyte differentiation Source: Ensembl
  • negative regulation of cell cycle G2/M phase transition Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • olfactory bulb interneuron development Source: MGI
  • olfactory bulb interneuron differentiation Source: MGI
  • olfactory lobe development Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • post-embryonic development Source: MGI
  • regulation of centrosome cycle Source: UniProtKB
  • regulation of gene expression Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-dependent transcription factor ATF-5
Short name:
cAMP-dependent transcription factor ATF-5
Alternative name(s):
Activating transcription factor 5-alpha/beta
BZIP protein ATF7
NAP1
NRIF3-associated protein
Transcription factor ATFx
Transcription factor-like protein ODA-10
Gene namesi
Name:Atf5
Synonyms:Atfx, Nap1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2141857. Atf5.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus 1 Publication
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity

  • Note: Actively transported to the centrosome and accumulated in the pericentriolar material (PCM) during G1 to M phase via a microtubule-dependent mechanism. During late telophase and cytokinesis, translocates from the centrosome to the midbody.By similarity

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

The majority of pups die within 48h after birth even if there is no major phenotypic differences at birth. Mice reveal a lack of milk in their stomach and show a dramatic loss of mature olfactory sensory neurons.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi29 – 291K → Q: Enhances interaction with CEBPB. 1 Publication
Mutagenesisi29 – 291K → R: Decreases acetylation levels and interaction with CEBPB. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 283283Cyclic AMP-dependent transcription factor ATF-5PRO_0000076587Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei29 – 291N6-acetyllysine; by EP3001 Publication

Post-translational modificationi

Acetylated at Lys-29 by EP300, the acetylation enhances the interaction with CEBPB, DNA-binding and transactivation activity.1 Publication
Ubiquitinated by CDC34 and UBE2B in order to be degraded by the proteasome. Cisplatin inhibits ubiquitination and proteasome-mediated degradation by inhibiting the interaction with CDC34. Ubiquitination and degradation by the proteasome are inhibited by NLK in a kinase-independent manner.By similarity
Phosphorylated by NLK, probably at Ser-92 and Ser-126.By similarity

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

PaxDbiO70191.
PRIDEiO70191.

PTM databases

PhosphoSiteiO70191.

Expressioni

Tissue specificityi

Highly expressed in liver and at lower levels in heart, brain, lung, kidney, adipose tissue, and skeletal muscle. Expressed in some immature and in all mature olfactory sensory neurons (at protein level) (PubMed:23090999).3 Publications

Developmental stagei

Expressed in sensory neurons during embryonic development of the olfactory epithelium and vomeronasal organ. From, at least, E11.5 through adulthood, expressed in the olfactory system. At E14.5, highly expressed in the olfactory epithelia, vomeronasal organ, the Grueneberg ganglion, the septal organ and the olfactory bulb (PubMed:23090999). At E14.5, expressed within germinal regions in the ventricular zone of the brain, the rhombic lip and the nascent external granule layer (EGL). At E16.5 expression at the EGL is more intense and extensive. From P1 to P15, expressed in cerebellar granule neuron progenitor cells (CGNPs) of the EGL (PubMed:22095825).3 Publications

Inductioni

Expressed in a circadian manner in the liver. Down-regulated by pro-apoptotic stimuli such IL3-deprivation that induce LCN2 expression (PubMed:12130540). In neural stem cells the expression is induced by retinoic acid (PubMed:23090999).3 Publications

Gene expression databases

BgeeiO70191.
CleanExiMM_ATF5.
ExpressionAtlasiO70191. baseline and differential.
GenevisibleiO70191. MM.

Interactioni

Subunit structurei

Binds DNA as a dimer. Interacts with PTP4A1/PRL-1 (By similarity). Interacts with CCND3, but not with CCND1 or CCND2. Interacts with HSPA1A or HSPA1B; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts (via C-terminal region) with NPM1 (via C-terminal region); the interaction leads to loss of association between HSPA1A or HSPA1B and ATF5 and promotes ATF5 degradation via proteasome-dependent and caspase-dependent processes. Interacts with NLK; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner. Interacts with alpha-tubulin, gamma-tubulin members TUBGCP2 and TUBGCP4, PCNT; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (By similarity). Interacts with CEBPB and EP300; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi223346. 2 interactions.
STRINGi10090.ENSMUSP00000047771.

Structurei

3D structure databases

ProteinModelPortaliO70191.
SMRiO70191. Positions 217-272.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini209 – 27264bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2121Required for protein stabilization induced by IL1BBy similarityAdd
BLAST
Regioni119 – 218100Interaction with PTP4A11 PublicationAdd
BLAST
Regioni211 – 23121Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni237 – 25115Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi123 – 13311Poly-ProAdd
BLAST

Sequence similaritiesi

Belongs to the bZIP family.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4571. Eukaryota.
ENOG4111ZXT. LUCA.
HOGENOMiHOG000004844.
HOVERGENiHBG003535.
InParanoidiO70191.
KOiK09044.
OMAiLAIYCRG.
OrthoDBiEOG7NCV54.
PhylomeDBiO70191.
TreeFamiTF316136.

Family and domain databases

InterProiIPR029855. ATF-5.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR13044:SF3. PTHR13044:SF3. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O70191-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLATLGLE LDRALLPASG LGWLVDYGKL PLAPAPLGPY EVLGGALEGG
60 70 80 90 100
LPGGGEPLAG DGFSDWMTER VDFTALLPLE APLPPGTLPP PSPAPPDLEA
110 120 130 140 150
MASLLKKELE QMEDFFLDAP LLPPPSPPPP PPPAAAPSLP LPLPLPTFDL
160 170 180 190 200
PQPPTLDTLD LLAVYCRSEA GPGDSGLSTL PVPQQPPPLA PLPSPARPAP
210 220 230 240 250
YPSPASTRGD RKQKKRDQNK SAALRYRQRK RAEGEALEGE CQGLEARNRE
260 270 280
LRERAESVER EIQYVKDLLI EVYKARSQRT RST
Length:283
Mass (Da):30,331
Last modified:February 21, 2001 - v2
Checksum:i01FA2D352F0590CC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti146 – 1461P → PLP in AAK00584 (PubMed:11278933).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF375475 mRNA. Translation: AAK54640.1.
AF375476 mRNA. Translation: AAK54641.1.
AF312938 mRNA. Translation: AAG34160.1.
AF310624 mRNA. Translation: AAL55820.1.
AY115107 Genomic DNA. Translation: AAM74470.1.
BC010195 mRNA. Translation: AAH10195.1.
BC092068 mRNA. Translation: AAH92068.1.
AY024362 mRNA. Translation: AAK00584.1.
AB012276 mRNA. Translation: BAA25313.1.
CCDSiCCDS21215.1.
RefSeqiNP_109618.1. NM_030693.2.
UniGeneiMm.389890.

Genome annotation databases

EnsembliENSMUST00000047356; ENSMUSP00000047771; ENSMUSG00000038539.
ENSMUST00000107893; ENSMUSP00000103525; ENSMUSG00000038539.
GeneIDi107503.
KEGGimmu:107503.
UCSCiuc009gqu.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF375475 mRNA. Translation: AAK54640.1.
AF375476 mRNA. Translation: AAK54641.1.
AF312938 mRNA. Translation: AAG34160.1.
AF310624 mRNA. Translation: AAL55820.1.
AY115107 Genomic DNA. Translation: AAM74470.1.
BC010195 mRNA. Translation: AAH10195.1.
BC092068 mRNA. Translation: AAH92068.1.
AY024362 mRNA. Translation: AAK00584.1.
AB012276 mRNA. Translation: BAA25313.1.
CCDSiCCDS21215.1.
RefSeqiNP_109618.1. NM_030693.2.
UniGeneiMm.389890.

3D structure databases

ProteinModelPortaliO70191.
SMRiO70191. Positions 217-272.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223346. 2 interactions.
STRINGi10090.ENSMUSP00000047771.

PTM databases

PhosphoSiteiO70191.

Proteomic databases

PaxDbiO70191.
PRIDEiO70191.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047356; ENSMUSP00000047771; ENSMUSG00000038539.
ENSMUST00000107893; ENSMUSP00000103525; ENSMUSG00000038539.
GeneIDi107503.
KEGGimmu:107503.
UCSCiuc009gqu.2. mouse.

Organism-specific databases

CTDi22809.
MGIiMGI:2141857. Atf5.

Phylogenomic databases

eggNOGiKOG4571. Eukaryota.
ENOG4111ZXT. LUCA.
HOGENOMiHOG000004844.
HOVERGENiHBG003535.
InParanoidiO70191.
KOiK09044.
OMAiLAIYCRG.
OrthoDBiEOG7NCV54.
PhylomeDBiO70191.
TreeFamiTF316136.

Miscellaneous databases

ChiTaRSiAtf5. mouse.
NextBioi358924.
PROiO70191.
SOURCEiSearch...

Gene expression databases

BgeeiO70191.
CleanExiMM_ATF5.
ExpressionAtlasiO70191. baseline and differential.
GenevisibleiO70191. MM.

Family and domain databases

InterProiIPR029855. ATF-5.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR13044:SF3. PTHR13044:SF3. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization, and odorant sensory neuron localization."
    Hansen M.B., Mitchelmore C., Kjaerulff K.M., Rasmussen T.E., Pedersen K.M., Jensen N.A.
    Genomics 80:344-350(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Brain.
  2. "Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia."
    Angata T., Kerr S.C., Greaves D.R., Varki N.M., Crocker P.R., Varki A.
    J. Biol. Chem. 277:24466-24474(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "The NRIF3-associated protein NAP1."
    Li D., Samuels H.H.
    Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver and Mammary gland.
  5. "ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase."
    Peters C.S., Liang X., Li S., Kannan S., Peng Y., Taub R., Diamond R.H.
    J. Biol. Chem. 276:13718-13726(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 67-283, DNA-BINDING, TISSUE SPECIFICITY, INTERACTION WITH PTP4A1.
    Tissue: Adipocyte.
  6. "cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein."
    Nishizawa M., Nagata S.
    FEBS Lett. 299:36-38(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 200-283.
  7. "Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors."
    Persengiev S.P., Devireddy L.R., Green M.R.
    Genes Dev. 16:1806-1814(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, FUNCTION.
  8. "cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene."
    Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A., Matsunaga N., Ohdo S.
    J. Biol. Chem. 286:32416-32423(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  9. "Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells."
    Lee H.Y., Angelastro J.M., Kenney A.M., Mason C.A., Greene L.A.
    Dev. Neurobiol. 72:789-804(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
  10. "Transcription factor ATF5 is required for terminal differentiation and survival of olfactory sensory neurons."
    Wang S.Z., Ou J., Zhu L.J., Green M.R.
    Proc. Natl. Acad. Sci. U.S.A. 109:18589-18594(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, INDUCTION BY RETINOIC ACID.
  11. "p300-dependent acetylation of activating transcription factor 5 enhances C/EBPbeta transactivation of C/EBPalpha during 3T3-L1 differentiation."
    Zhao Y., Zhang Y.D., Zhang Y.Y., Qian S.W., Zhang Z.C., Li S.F., Guo L., Liu Y., Wen B., Lei Q.Y., Tang Q.Q., Li X.
    Mol. Cell. Biol. 34:315-324(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CEBPB AND EP300, ACETYLATION AT LYS-29, MUTAGENESIS OF LYS-29.

Entry informationi

Entry nameiATF5_MOUSE
AccessioniPrimary (citable) accession number: O70191
Secondary accession number(s): Q58E51, Q99NH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: May 11, 2016
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.