PPP1R15A

PPP1R15A is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation.

Protein Phosphatase 1 Regulatory Subunit 15A

Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress (PubMed:26742780, PubMed:26095357).
Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1 (PubMed:14718519).
May promote apoptosis by inducing p53/TP53 phosphorylation on 'Ser-15' (PubMed:14635196).
Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux (PubMed:32978159).
Acts also a viral restriction factor by attenuating HIV-1 replication (PubMed:31778897).
Mechanistically, mediates the inhibition of HIV-1 TAR RNA-mediated translation (PubMed:31778897).
(Microbial infection) Promotes enterovirus 71 replication by mediating the internal ribosome entry site (IRES) activity of viral 5'-UTR.

Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentTAS:ProtInc
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of PERK-mediated unfolded protein responseManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of phosphoprotein phosphatase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein dephosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of peptidyl-serine dephosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of phosphoprotein phosphatase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of translational initiation in response to stress1 PublicationIC:ParkinsonsUK-UCL
Protein localization to endoplasmic reticulumManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of cell cycleManual Assertion Based On ExperimentTAS:ProtInc
Regulation of translational initiation by eIF2 alpha dephosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Response to endoplasmic reticulum stressManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL

Endoplasmic reticulum membrane
Mitochondrion outer membrane
Associates with membranes via an N-terminal amphipathic intramembrane region.

Cytoplasmic: 1-21
Helical: 22-39
Cytoplasmic: 40-674

Phosphorylated at multiple Ser/Thr residues. Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Phosphorylation at Tyr-262 enhances proteasomal degradation, this position is dephosphorylated by PTPN2.
Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association.