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Protein

Cyclic AMP-dependent transcription factor ATF-4

Gene

Atf4

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

Functioni

Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to ER stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes.7 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processBiological rhythms, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-dependent transcription factor ATF-4
Short name:
cAMP-dependent transcription factor ATF-4
Alternative name(s):
Activating transcription factor 4
C/EBP-related ATF
Short name:
C/ATF
Tax-responsive enhancer element-binding protein 67 homolog
Short name:
TaxREB67 homolog
Gene namesi
Name:Atf4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:88096 Atf4

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

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Null mice exhibit an increase in serum insulin levels and low blood glucose levels. There is a decrease in total fat content, gonadal fat, lean mass and body weight. Serum levels of osteocalcin/BGLAP are decreased. PBK/AKT1-mediated phosphorylation of FOXO1 at 'Ser-258' is increased with a subsequent decrease of FOXO1-mediated transcriptional activity.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi212T → A: Promotes stabilization due to impaired ubiquitination; when associated with A-223; A-230; A-234 and A-247. 1 Publication1
Mutagenesisi218S → A: Promotes stabilization due to impaired ubiquitination. 1 Publication1
Mutagenesisi223S → A: Promotes stabilization due to impaired ubiquitination; when associated with A-212; A-230; A-234 and A-247. 1 Publication1
Mutagenesisi230S → A: Promotes stabilization due to impaired ubiquitination; when associated with A-212; A-223; A-234 and A-247. 1 Publication1
Mutagenesisi234S → A: Promotes stabilization due to impaired ubiquitination; when associated with A-212; A-223; A-230 and A-247. 1 Publication1
Mutagenesisi247S → A: Promotes stabilization due to impaired ubiquitination; when associated with A-212; A-223; A-230 and A-234. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765851 – 349Cyclic AMP-dependent transcription factor ATF-4Add BLAST349

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei212Phosphothreonine1 Publication1
Modified residuei218Phosphoserine1 Publication1
Modified residuei223Phosphoserine1 Publication1
Modified residuei230Phosphoserine1 Publication1
Modified residuei234Phosphoserine1 Publication1
Modified residuei247Phosphoserine1 Publication1
Cross-linki258Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4.1 Publication
Phosphorylated by NEK6 (By similarity). Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination. Phosphorylation is promoted by mTORC1.By similarity1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ06507
PRIDEiQ06507

PTM databases

iPTMnetiQ06507
PhosphoSitePlusiQ06507

Expressioni

Developmental stagei

At E16.5, expressed in osteoblasts surrounding newly formed trabecular bone. At postnatal day 2, detected in most osteoblasts and lining cells. By postnatal week 4, is detected in fewer osteoblasts, but remains present in lining cells (at protein level).1 Publication

Inductioni

By ER stress. Expressed in a circadian manner in the liver with an increased expression seen during the light phase. Expressed in a circadian manner in the midbrain with an increased expression seen during the dark phase (at protein level). Expressed in a circadian manner also in the suprachiasmatic nucleus (SCN) of the brain, cerebral cortex, kidney and small intestine.3 Publications

Gene expression databases

BgeeiENSMUSG00000042406
CleanExiMM_ATF4
GenevisibleiQ06507 MM

Interactioni

Subunit structurei

Binds DNA as a homodimer and as a heterodimer (By similarity). Interacts with CEBPB and binds DNA as a heterodimer with CEBPB (PubMed:11018027). Interacts with CEP290 (via an N-terminal region). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3. Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (By similarity). Forms a heterodimer with TXLNG in osteoblasts (PubMed:15911876). Interacts (via its DNA binding domain) with FOXO1 (C-terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production (PubMed:22298775). Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (PubMed:16751105). Interacts with DDIT3/CHOP (By similarity). Interacts with ABRAXAS2 (PubMed:22974638).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198235, 11 interactors
ComplexPortaliCPX-6 ATF4-CREB1 transcription factor complex
CPX-7 ATF1-ATF4 transcription factor complex
CORUMiQ06507
DIPiDIP-30969N
IntActiQ06507, 9 interactors
STRINGi10090.ENSMUSP00000105234

Structurei

3D structure databases

ProteinModelPortaliQ06507
SMRiQ06507
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini276 – 339bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni278 – 298Basic motifPROSITE-ProRule annotationAdd BLAST21
Regioni303 – 339Interaction with GABBR1By similarityAdd BLAST37
Regioni304 – 332Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi214 – 223BetaTrCP degron motif10

Domaini

The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.1 Publication

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiKOG4571 Eukaryota
ENOG4111ZXT LUCA
GeneTreeiENSGT00530000063801
HOVERGENiHBG004301
InParanoidiQ06507
KOiK04374
OMAiAFSGMDW
OrthoDBiEOG091G0FNW
TreeFamiTF316136

Family and domain databases

InterProiView protein in InterPro
IPR029811 ATF4
IPR004827 bZIP
PANTHERiPTHR13044:SF2 PTHR13044:SF2, 1 hit
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
PS00036 BZIP_BASIC, 1 hit

Sequencei

Sequence statusi: Complete.

Q06507-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEMSFLNSE VLAGDLMSPF DQSGLGAEES LGLLDDYLEV AKHLKPHGFS
60 70 80 90 100
SDKAGSSEWP AMDDGLASAS DTGKEDAFSG TDWMLEKMDL KEFDFDALFR
110 120 130 140 150
MDDLETMPDE LLTTLDDTCD LFAPLVQETN KEPPQTVNPI GHLPESLIKV
160 170 180 190 200
DQVAPFTFLQ PFPCSPGVLS STPEHSFSLE LGSEVDISEG DRKPDSAAYI
210 220 230 240 250
TLIPPCVKEE DTPSDNDSGI CMSPESYLGS PQHSPSTSRA PPDNLPSPGG
260 270 280 290 300
SRGSPRPKPY DPPGVSLTAK VKTEKLDKKL KKMEQNKTAA TRYRQKKRAE
310 320 330 340
QEALTGECKE LEKKNEALKE KADSLAKEIQ YLKDLIEEVR KARGKKRVP
Length:349
Mass (Da):38,355
Last modified:July 27, 2011 - v2
Checksum:i0C3F895755B1C7B9
GO

Sequence cautioni

The sequence AAA53043 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti345K → Q in AAA40476 (PubMed:8506317).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13791 mRNA Translation: AAA40476.1
M94087 mRNA Translation: AAA53043.1 Different initiation.
AK138657 mRNA Translation: BAE23736.1
AK144777 mRNA Translation: BAE26060.1
AK146193 mRNA Translation: BAE26967.1
AK156298 mRNA Translation: BAE33662.1
CH466550 Genomic DNA Translation: EDL04604.1
CH466550 Genomic DNA Translation: EDL04605.1
BC085169 mRNA Translation: AAH85169.1
CCDSiCCDS37145.1
RefSeqiNP_001274109.1, NM_001287180.1
NP_033846.2, NM_009716.3
UniGeneiMm.641

Genome annotation databases

EnsembliENSMUST00000109605; ENSMUSP00000105234; ENSMUSG00000042406
GeneIDi11911
KEGGimmu:11911
UCSCiuc007wvl.2 mouse

Similar proteinsi

Entry informationi

Entry nameiATF4_MOUSE
AccessioniPrimary (citable) accession number: Q06507
Secondary accession number(s): Q5U4B2, Q61906
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 143 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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