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Protein

Cyclic AMP-dependent transcription factor ATF-5

Gene

ATF5

Organism
Homo sapiens (Human)
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 (PubMed:10373550, PubMed:15358120, PubMed:21212266, PubMed:20654631). Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4 (PubMed:15358120). 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 (By similarity). Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation (By similarity). Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes (By similarity). May be involved in osteogenic differentiation (PubMed:22442021). 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 (PubMed:21791614). Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent (By similarity). Cooperates with NR1I3/CAR in the transcriptional activation of CYP2B6 in liver (PubMed:18332083). In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2/M phase (PubMed:22528486, PubMed:18701499). May act as a negative regulator of IL1B transduction pathway in liver (PubMed:24379400). Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation (PubMed:24216764). 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 (PubMed:26213385).By similarity13 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • DNA binding transcription factor activity Source: UniProtKB
  • kinase binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcription corepressor activity Source: ProtInc
  • transcription regulatory region DNA binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

GO - Biological processi

  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • circadian rhythm Source: Ensembl
  • fat cell differentiation Source: UniProtKB
  • multicellular organism growth Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • 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: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: NTNU_SB
  • post-embryonic development Source: Ensembl
  • regulation of centrosome cycle Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription by RNA polymerase II Source: ProtInc

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

SIGNORiQ9Y2D1

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
Transcription factor ATFx
Gene namesi
Name:ATF5
Synonyms:ATFX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000169136.8
HGNCiHGNC:790 ATF5
MIMi606398 gene
neXtProtiNX_Q9Y2D1

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3 – 25LLATL…LGWLV → AAATAGAEADRAAAPASGAG WAA: Highly increases protein levels. No effect on protein stability enhanced by IL1B. 1 PublicationAdd BLAST23
Mutagenesisi3 – 4LL → AA: Increases protein levels. No effect on protein stability enhanced by IL1B. 1 Publication2
Mutagenesisi3 – 4LL → II: Decreases protein levels. 1 Publication2
Mutagenesisi3 – 4LL → VV: No effect on protein levels. No effect on protein stability enhanced by IL1B. 1 Publication2
Mutagenesisi7L → A: Increases protein levels. 1 Publication1
Mutagenesisi9 – 11LEL → AEA: Increases protein levels. 1 Publication3
Mutagenesisi15 – 16LL → AA: Increases protein levels. 1 Publication2
Mutagenesisi21 – 25LGWLV → AGWAA: Increases protein levels. 1 Publication5
Mutagenesisi92 – 94SPT → APA: Not phosphorylated; when associated with A-126 and A-190. 3
Mutagenesisi126S → A: Not phosphorylated; when associated with 92-A--A-94 and A-190. 1
Mutagenesisi157D → A: Resistant to cleavage by CASP3. 1 Publication1
Mutagenesisi190S → A: Not phosphorylated; when associated with 92-A--A-94 and A-126. 1

Organism-specific databases

DisGeNETi22809
OpenTargetsiENSG00000169136
PharmGKBiPA25090

Chemistry databases

DrugBankiDB00852 Pseudoephedrine

Polymorphism and mutation databases

BioMutaiATF5
DMDMi308153647

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765861 – 282Cyclic AMP-dependent transcription factor ATF-5Add BLAST282

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29N6-acetyllysine; by EP300By similarity1
Modified residuei256PhosphoserineCombined sources1

Post-translational modificationi

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 (PubMed:18458088). Ubiquitination and degradation by the proteasome are inhibited by NLK in a kinase-independent manner (PubMed:25512613).4 Publications
Phosphorylated by NLK, probably at Ser-92, Thr-94, Ser-126 and Ser-190.1 Publication
Acetylated at Lys-29 by EP300, the acetylation enhances the interaction with CEBPB, DNA-binding and transactivation activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9Y2D1
PeptideAtlasiQ9Y2D1
PRIDEiQ9Y2D1
TopDownProteomicsiQ9Y2D1

PTM databases

iPTMnetiQ9Y2D1
PhosphoSitePlusiQ9Y2D1

Expressioni

Tissue specificityi

Widely expressed with higher expression levels in liver.1 Publication

Inductioni

Down-regulated by pro-apoptotic stimuli (PubMed:21212266). However, the pro-apoptotic cisplatin increases protein levels by inhibiting polyubiquitination (PubMed:18458088). IL1B increases protein levels through protein stabilization and increase of translation efficiency (PubMed:24379400).3 Publications

Gene expression databases

BgeeiENSG00000169136
CleanExiHS_ATF5
ExpressionAtlasiQ9Y2D1 baseline and differential
GenevisibleiQ9Y2D1 HS

Organism-specific databases

HPAiHPA030187

Interactioni

Subunit structurei

Binds DNA as a dimer. Interacts with PTP4A1/PRL-1 (By similarity). Interacts with CCND3, but not with CCND1 or CCND2 (PubMed:15358120). 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 (PubMed:22528486, PubMed:24379400). Interacts with NLK; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner (PubMed:25512613). 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 (PubMed:26213385). Interacts with CEBPB and EP300; EP300 is required for ATF5 and CEBPB interaction and DNA binding (By similarity).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116487, 10 interactors
IntActiQ9Y2D1, 14 interactors
STRINGi9606.ENSP00000396954

Structurei

3D structure databases

ProteinModelPortaliQ9Y2D1
SMRiQ9Y2D1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini208 – 271bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 21Required for protein stabilization induced by IL1B1 PublicationAdd BLAST21
Regioni119 – 217Interaction with PTP4A1Add BLAST99
Regioni210 – 230Basic motifPROSITE-ProRule annotationAdd BLAST21
Regioni236 – 250Leucine-zipperPROSITE-ProRule annotationAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi123 – 139Poly-ProAdd BLAST17
Compositional biasi186 – 194Poly-Pro9

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiKOG4571 Eukaryota
ENOG4111ZXT LUCA
GeneTreeiENSGT00530000063801
HOGENOMiHOG000004844
HOVERGENiHBG003535
InParanoidiQ9Y2D1
KOiK09044
OMAiLAIYCRG
OrthoDBiEOG091G0SPB
PhylomeDBiQ9Y2D1
TreeFamiTF316136

Family and domain databases

InterProiView protein in InterPro
IPR029855 ATF5
IPR004827 bZIP
PANTHERiPTHR13044:SF3 PTHR13044:SF3, 3 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.

Q9Y2D1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLATLGLE LDRALLPASG LGWLVDYGKL PPAPAPLAPY EVLGGALEGG
60 70 80 90 100
LPVGGEPLAG DGFSDWMTER VDFTALLPLE PPLPPGTLPQ PSPTPPDLEA
110 120 130 140 150
MASLLKKELE QMEDFFLDAP PLPPPSPPPL PPPPLPPAPS LPLSLPSFDL
160 170 180 190 200
PQPPVLDTLD LLAIYCRNEA GQEEVGMPPL PPPQQPPPPS PPQPSRLAPY
210 220 230 240 250
PHPATTRGDR KQKKRDQNKS AALRYRQRKR AEGEALEGEC QGLEARNREL
260 270 280
KERAESVERE IQYVKDLLIE VYKARSQRTR SC
Length:282
Mass (Da):30,674
Last modified:October 5, 2010 - v4
Checksum:iDDB2F907CA0215A0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti161 – 163LLA → RHE in AAD28370 (PubMed:10373550).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022786121P → L2 PublicationsCorresponds to variant dbSNP:rs283526Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305687 mRNA Translation: AAG22558.1
AB073613 mRNA Translation: BAD38650.1
AB021663 mRNA Translation: BAA78477.2
AK024402 mRNA Translation: BAG51295.1
AC011452 Genomic DNA No translation available.
CH471177 Genomic DNA Translation: EAW52581.1
BC005174 mRNA Translation: AAH05174.1
AF101388 mRNA Translation: AAD28370.1
CCDSiCCDS12789.1
RefSeqiNP_001180575.1, NM_001193646.1
NP_001277675.1, NM_001290746.1
NP_036200.2, NM_012068.5
XP_011524931.1, XM_011526629.2
UniGeneiHs.9754

Genome annotation databases

EnsembliENST00000423777; ENSP00000396954; ENSG00000169136
ENST00000595125; ENSP00000470633; ENSG00000169136
GeneIDi22809
KEGGihsa:22809
UCSCiuc002prd.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiATF5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2D1
Secondary accession number(s): B3KND3, Q9BSA1, Q9UNQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 5, 2010
Last modified: March 28, 2018
This is version 156 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health