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MGP000231

UniProt Annotations

Entry Information
Gene Nameactivating transcription factor 4
Protein EntryATF4_HUMAN
UniProt IDP18848
SpeciesHuman
Comments
Comment typeDescription
DomainThe BetaTrCP degron motif promotes binding to BTRC when phosphorylated. {ECO:0000250}.
FunctionTranscriptional 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). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. 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. {ECO:0000250, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:18940792}.
InteractionQ9Y297:BTRC; NbExp=4; IntAct=EBI-492498, EBI-307461; Q9Y297-2:BTRC; NbExp=5; IntAct=EBI-492498, EBI-8826333; Q9NS37:CREBZF; NbExp=5; IntAct=EBI-492498, EBI-632965; Q9UIK4-2:DAPK2; NbExp=2; IntAct=EBI-492498, EBI-9693115; O54784:Dapk3 (xeno); NbExp=2; IntAct=EBI-492498, EBI-77359; Q9NRI5:DISC1; NbExp=3; IntAct=EBI-492498, EBI-529989; P05412:JUN; NbExp=2; IntAct=EBI-492498, EBI-852823; Q96RU7:TRIB3; NbExp=2; IntAct=EBI-492498, EBI-492476;
PtmPhosphorylated by NEK6 (By similarity). Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination. Phosphorylation is promoted by mTORC1 (By similarity). {ECO:0000250}.
PtmPhosphorylated by NEK6. {ECO:0000269|PubMed:20873783}.
PtmUbiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4. {ECO:0000250}.
SimilarityBelongs to the bZIP family. {ECO:0000305}.
SimilarityContains 1 bZIP (basic-leucine zipper) domain. {ECO:0000255|PROSITE-ProRule:PRU00978}.
Subcellular LocationCytoplasm. Cell membrane. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Co- localizes with NEK6 in the centrosome. {ECO:0000250}.
SubunitBinds DNA as a homo- or heterodimer. Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C- termini). 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 NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3. Forms a heterodimer with TXLNG in osteoblasts. Interacts with DDIT3/CHOP. {ECO:0000250, ECO:0000269|PubMed:11018027, ECO:0000269|PubMed:15911876, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21408167}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ATF4ID44413ch22q13.html";
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