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Protein

Cyclic AMP-dependent transcription factor ATF-4

Gene

Atf4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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
Short name:
rATF-4
Gene namesi
Name:Atf4Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi621863. Atf4.

Subcellular locationi

GO - Cellular componenti

  • ATF1-ATF4 transcription factor complex Source: Ensembl
  • ATF4-CREB1 transcription factor complex Source: Ensembl
  • CHOP-ATF4 complex Source: Ensembl
  • cytoplasm Source: RGD
  • dendrite membrane Source: RGD
  • Lewy body core Source: Ensembl
  • microtubule organizing center Source: UniProtKB-SubCell
  • nuclear periphery Source: Ensembl
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 347347Cyclic AMP-dependent transcription factor ATF-4PRO_0000258022Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei211 – 2111PhosphothreonineBy similarity
Modified residuei217 – 2171PhosphoserineBy similarity
Modified residuei222 – 2221PhosphoserineBy similarity
Modified residuei229 – 2291PhosphoserineBy similarity
Modified residuei233 – 2331PhosphoserineBy similarity
Modified residuei246 – 2461PhosphoserineBy 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.By similarity
Phosphorylated by NEK6 (By similarity). Phosphorylated on the betaTrCP degron motif at Ser-217, followed by phosphorylation at Thr-211, Ser-222, Ser-229, Ser-233 and Ser-246, promoting interaction with BTRC and ubiquitination. Phosphorylation is promoted by mTORC1 (By similarity).By similarity
Phosphorylated by NEK6.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9ES19.
PRIDEiQ9ES19.

PTM databases

PhosphoSiteiQ9ES19.

Expressioni

Tissue specificityi

Expressed in brain, heart, liver, spleen, lung and muscle, but not testis.1 Publication

Gene expression databases

ExpressionAtlasiQ9ES19. baseline and differential.
GenevisibleiQ9ES19. RN.

Interactioni

Subunit structurei

Binds DNA as a homodimer and as a heterodimer. Interacts with CEBPB and binds DNA as a heterodimer with CEBPB. Interacts with NEK6, DAPK2 and ZIPK/DAPK3 (By similarity). Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (PubMed:10924501). Forms a heterodimer with TXLNG in osteoblasts. 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. Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (By similarity). Interacts with CEP290 (via an N-terminal region). Interacts with DDIT3/CHOP (By similarity).By similarity1 Publication

GO - Molecular functioni

  • protein C-terminus binding Source: RGD
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi249453. 2 interactions.
IntActiQ9ES19. 1 interaction.
STRINGi10116.ENSRNOP00000060302.

Structurei

3D structure databases

ProteinModelPortaliQ9ES19.
SMRiQ9ES19. Positions 282-337.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini274 – 33764bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni276 – 29621Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni301 – 33737Interaction with GABBR11 PublicationAdd
BLAST
Regioni302 – 33029Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi213 – 22210BetaTrCP degron motif

Domaini

The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG4571. Eukaryota.
ENOG4111ZXT. LUCA.
GeneTreeiENSGT00530000063801.
HOGENOMiHOG000004844.
HOVERGENiHBG004301.
InParanoidiQ9ES19.
KOiK04374.
OMAiAFSGMDW.
OrthoDBiEOG72JWGW.
PhylomeDBiQ9ES19.

Family and domain databases

InterProiIPR029811. ATF4.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR13044:SF2. PTHR13044:SF2. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9ES19-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEMSFLNSE VLAGDLMSPF DQSGLGAEES LGLLDDYLEV AKHFKPHGFS
60 70 80 90 100
SDKAGSSEWL AMDGLVSASD TGKEDAFSGT DWMLEKMDLK EFDFDALFRM
110 120 130 140 150
DDLETMPDEL LATLDDTCDL FAPLVQETNK EPPQTVNPIG HLPESVIKVD
160 170 180 190 200
QAAPFTFLQP LPCSPGFLSS TPDHSFSLEL GSEVDISEGD RKPDSAAYIT
210 220 230 240 250
LTPQCVKEED TPSDSDSGIC MSPESYLGSP QHSPSTSRAP PDSLPSPGVP
260 270 280 290 300
RGSRPKPYDP PGVSVTAKVK TEKLDKKLKK MEQNKTAATR YRQKKRAEQE
310 320 330 340
ALTGECKELE KKNEALKEKA DSLAKEIQYL KDLIEEVRKA RGKKRVP
Length:347
Mass (Da):38,152
Last modified:March 1, 2001 - v1
Checksum:iCCE6BD02F263296B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF252627 mRNA. Translation: AAG31732.1.
RefSeqiNP_077379.1. NM_024403.2.
UniGeneiRn.2423.

Genome annotation databases

EnsembliENSRNOT00000065304; ENSRNOP00000060302; ENSRNOG00000017801.
GeneIDi79255.
KEGGirno:79255.
UCSCiRGD:621863. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF252627 mRNA. Translation: AAG31732.1.
RefSeqiNP_077379.1. NM_024403.2.
UniGeneiRn.2423.

3D structure databases

ProteinModelPortaliQ9ES19.
SMRiQ9ES19. Positions 282-337.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249453. 2 interactions.
IntActiQ9ES19. 1 interaction.
STRINGi10116.ENSRNOP00000060302.

PTM databases

PhosphoSiteiQ9ES19.

Proteomic databases

PaxDbiQ9ES19.
PRIDEiQ9ES19.

Protocols and materials databases

DNASUi79255.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000065304; ENSRNOP00000060302; ENSRNOG00000017801.
GeneIDi79255.
KEGGirno:79255.
UCSCiRGD:621863. rat.

Organism-specific databases

CTDi468.
RGDi621863. Atf4.

Phylogenomic databases

eggNOGiKOG4571. Eukaryota.
ENOG4111ZXT. LUCA.
GeneTreeiENSGT00530000063801.
HOGENOMiHOG000004844.
HOVERGENiHBG004301.
InParanoidiQ9ES19.
KOiK04374.
OMAiAFSGMDW.
OrthoDBiEOG72JWGW.
PhylomeDBiQ9ES19.

Miscellaneous databases

PROiQ9ES19.

Gene expression databases

ExpressionAtlasiQ9ES19. baseline and differential.
GenevisibleiQ9ES19. RN.

Family and domain databases

InterProiIPR029811. ATF4.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR13044:SF2. PTHR13044:SF2. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The metabotropic GABAB receptor directly interacts with the activating transcription factor 4."
    Nehring R.B., Horikawa H.P.M., El Far O., Kneussel M., Brandstatter J.H., Stamm S., Wischmeyer E., Betz H., Karschin A.
    J. Biol. Chem. 275:35185-35191(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH GABBR1 AND GABBR2, SUBCELLULAR LOCATION.
    Tissue: Brain1 Publication.
  2. "C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements."
    Vallejo M., Ron D., Miller C.P., Habener J.F.
    Proc. Natl. Acad. Sci. U.S.A. 90:4679-4683(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiATF4_RAT
AccessioniPrimary (citable) accession number: Q9ES19
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 110 of the entry and version 1 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. 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.