UniProt functional annotation for O75807



	UniProt functional annotation for O75807

UniProt code: O75807.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Recruits 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}.

Subunit: Interacts 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}.

Subcellular location: Endoplasmic 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}.

Induction: Specifically produced in response to stress: in absence of stress, some upstream open reading frame (uORF) of this transcript is translated, thereby preventing its translation (PubMed:19131336). By methyl methanesulfonate and ionizing irradiation (PubMed:9153226). By IL24/interleukin-24 in melanoma cells; which induces apoptosis (PubMed:10490642, PubMed:12114539). {ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12114539, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:9153226}.

Ptm: 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. {ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:24092754}.

Ptm: Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association. {ECO:0000269|PubMed:24092754}.

Miscellaneous: The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.

Similarity: Belongs to the PPP1R15 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Recruits 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}.


Subunit:		Interacts 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}.
Subcellular location:		Endoplasmic 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}.
Induction:		Specifically produced in response to stress: in absence of stress, some upstream open reading frame (uORF) of this transcript is translated, thereby preventing its translation (PubMed:19131336). By methyl methanesulfonate and ionizing irradiation (PubMed:9153226). By IL24/interleukin-24 in melanoma cells; which induces apoptosis (PubMed:10490642, PubMed:12114539). {ECO:0000269\|PubMed:10490642, ECO:0000269\|PubMed:12114539, ECO:0000269\|PubMed:19131336, ECO:0000269\|PubMed:9153226}.
Ptm:		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. {ECO:0000269\|PubMed:11517336, ECO:0000269\|PubMed:24092754}.
Ptm:		Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association. {ECO:0000269\|PubMed:24092754}.
Miscellaneous:		The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.
Similarity:		Belongs to the PPP1R15 family. {ECO:0000305}.