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Protein

Cyclic AMP-dependent transcription factor ATF-5

Gene

Atf5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 transcriptional 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: MGI
  • negative regulation of cell cycle G2/M phase transition Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of neurogenesis Source: MGI
  • 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 by RNA polymerase II 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 by RNA polymerase II Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2141857 Atf5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi29K → Q: Enhances interaction with CEBPB. 1 Publication1
Mutagenesisi29K → R: Decreases acetylation levels and interaction with CEBPB. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765871 – 283Cyclic AMP-dependent transcription factor ATF-5Add BLAST283

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29N6-acetyllysine; by EP3001 Publication1
Modified residuei257PhosphoserineBy similarity1

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, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO70191
PRIDEiO70191

PTM databases

iPTMnetiO70191
PhosphoSitePlusiO70191

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

BgeeiENSMUSG00000038539
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 interactors
STRINGi10090.ENSMUSP00000047771

Structurei

3D structure databases

ProteinModelPortaliO70191
SMRiO70191
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 272bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 21Required for protein stabilization induced by IL1BBy similarityAdd BLAST21
Regioni119 – 218Interaction with PTP4A11 PublicationAdd BLAST100
Regioni211 – 231Basic motifPROSITE-ProRule annotationAdd BLAST21
Regioni237 – 251Leucine-zipperPROSITE-ProRule annotationAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi123 – 133Poly-ProAdd BLAST11

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiKOG4571 Eukaryota
ENOG4111ZXT LUCA
GeneTreeiENSGT00530000063801
HOGENOMiHOG000004844
HOVERGENiHBG003535
InParanoidiO70191
KOiK09044
OMAiLAIYCRG
OrthoDBiEOG091G0SPB
PhylomeDBiO70191
TreeFamiTF316136

Family and domain databases

InterProiView protein in InterPro
IPR029855 ATF5
IPR004827 bZIP
PANTHERiPTHR13044:SF3 PTHR13044:SF3, 2 hits
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti146P → PLP in AAK00584 (PubMed:11278933).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiATF5_MOUSE
AccessioniPrimary (citable) accession number: O70191
Secondary accession number(s): Q58E51, Q99NH6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: June 20, 2018
This is version 142 of the entry and version 2 of the sequence. See 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

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