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MGP004729

UniProt Annotations

Entry Information
Gene Nameprotein phosphatase 1, regulatory subunit 15A
Protein EntryPR15A_HUMAN
UniProt IDO75807
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O75807-1; Sequence=Displayed; Name=2; IsoId=O75807-2; Sequence=VSP_057083, VSP_057084; Note=No experimental confirmation available.;
FunctionRecruits the serine/threonine-protein phosphatase PP1 to dephosphorylate 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. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15'. {ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12556489, ECO:0000269|PubMed:14635196, ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:8139541}.
InductionBy methyl methanesulfonate and ionizing irradiation. By IL24/interleukin-24 in melanoma cells; which induces apoptosis. {ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12114539, ECO:0000269|PubMed:9153226}.
InteractionP56545:CTBP2; NbExp=2; IntAct=EBI-714746, EBI-741533; Q13522:PPP1R1A; NbExp=4; IntAct=EBI-714746, EBI-1568511;
MiscellaneousThe phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.
PtmPhosphorylated 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. {ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:24092754}.
PtmPolyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association. {ECO:0000269|PubMed:24092754}.
SimilarityBelongs to the PPP1R15 family. {ECO:0000305}.
Subcellular LocationEndoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:12556489, ECO:0000269|PubMed:21518769}. Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:21518769}. Note=Associates with membranes via an N-terminal amphipathic intramembrane region. {ECO:0000269|PubMed:21518769}.
SubunitInteracts with PCNA (By similarity). Interacts with LYN and KMT2A/MLL1. Interacts with PP1, PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1. {ECO:0000250, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12016208, ECO:0000269|PubMed:12724406, ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:15705855}.
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