P17564 · PR15A_MOUSE
- ProteinProtein phosphatase 1 regulatory subunit 15A
- GenePpp1r15a
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids657 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:11381086, PubMed:12824288).
Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1 (By similarity).
May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15' (By similarity).
Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux (By similarity).
Acts also a viral restriction factor by attenuating vesicular stomatitis virus (VSV) replication (PubMed:17670836).
Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1 (By similarity).
May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15' (By similarity).
Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux (By similarity).
Acts also a viral restriction factor by attenuating vesicular stomatitis virus (VSV) replication (PubMed:17670836).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameProtein phosphatase 1 regulatory subunit 15A
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP17564
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Mitochondrion outer membrane ; Peripheral membrane protein
Note: Associates with membranes via an N-terminal amphipathic intramembrane region.
Features
Showing features for topological domain, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-21 | Cytoplasmic | ||||
Sequence: MAPSPRPQHVLHWRDAHNFYL | ||||||
Intramembrane | 22-39 | Helical | ||||
Sequence: LSPLMGLLSRAWSRLRGP | ||||||
Topological domain | 40-657 | Cytoplasmic | ||||
Sequence: EVPEAWLAKTVTGADQIEAAALLTPTPVSGNLLPHGETEESGSPEQSQAAQRLCLVEAESSPPETWGLSNVDEYNAKPGQDDLREKEMERTAGKATLQPAGLQGADKRLGEVVAREEGVAEPAYPTSQLEGGPAENEEDGETVKTYQASAASIAPGYKPSTPVPFLGEAEHQATEEKGTENKADPSNSPSSGSHSRAWEYYSREKPKQEGEAKVEAHRAGQGHPCRNAEAEEGGPETTFVCTGNAFLKAWVYRPGEDTEEEDNSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSPFLKAWVYRPGEDTEDDTEEEEDSENVAPGDSETADSSQSPCLQPQRCLPGEKTKGRGEEPPLFQVAFYLPGEKPESPWAAPKLPLRLQRRLRLFKAPTRDQDPEIPLKARKVHFAEKVTVHFLAVWAGPAQAARRGPWEQFARDRSRFARRIAQAEEKLGPYLTPDSRARAWARLRNPSLPQSEPRSSSEATPLTQDVTTPSPLPSETPSPSLYLGGRRG |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice display abnormal erythrocytes and reduced hemoglobin content due to defects in hemoglobin synthesis.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 549 | Abolishes interaction with PP1. | ||||
Sequence: V → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 65 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000096665 | 1-657 | Protein phosphatase 1 regulatory subunit 15A | |||
Sequence: MAPSPRPQHVLHWRDAHNFYLLSPLMGLLSRAWSRLRGPEVPEAWLAKTVTGADQIEAAALLTPTPVSGNLLPHGETEESGSPEQSQAAQRLCLVEAESSPPETWGLSNVDEYNAKPGQDDLREKEMERTAGKATLQPAGLQGADKRLGEVVAREEGVAEPAYPTSQLEGGPAENEEDGETVKTYQASAASIAPGYKPSTPVPFLGEAEHQATEEKGTENKADPSNSPSSGSHSRAWEYYSREKPKQEGEAKVEAHRAGQGHPCRNAEAEEGGPETTFVCTGNAFLKAWVYRPGEDTEEEDNSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSPFLKAWVYRPGEDTEDDTEEEEDSENVAPGDSETADSSQSPCLQPQRCLPGEKTKGRGEEPPLFQVAFYLPGEKPESPWAAPKLPLRLQRRLRLFKAPTRDQDPEIPLKARKVHFAEKVTVHFLAVWAGPAQAARRGPWEQFARDRSRFARRIAQAEEKLGPYLTPDSRARAWARLRNPSLPQSEPRSSSEATPLTQDVTTPSPLPSETPSPSLYLGGRRG | ||||||
Modified residue | 239 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 368 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 406 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 505 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated at multiple Ser/Thr residues. Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Phosphorylation at Tyr-239 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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed strongly in spleen and lung, moderately in thymus and muscle, and weakly in brain.
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 IL6 and various endoplasmic stresses such as methyl methanesulfonate (PubMed:12606582, PubMed:12824288, PubMed:8139541).
By IL6 and various endoplasmic stresses such as methyl methanesulfonate (PubMed:12606582, PubMed:12824288, PubMed:8139541).
(Microbial infection) By infection with various viruses such as vesicular stomatitis virus (VSV).
Developmental stage
Expression starts at 8.5 dpc, and decreases to undetectable levels at 10.5 dpc and 11.5 dpc. Expression is strongly up-regulated at 12.5 dpc, decreases at 16.5 dpc and reappears at 18.5 dpc. At 12.5 dpc, ubiquitously expressed, with high levels in brain, spinal cord, tongue, lung and genital tubercle.
Gene expression databases
Interaction
Subunit
Interacts with PPP1CA (PubMed:11381086, PubMed:9023344).
Interacts with EIF2S1 (By similarity).
Interacts with PCNA (PubMed:9371605).
Interacts with LYN and KMT2A/MLL1 (PubMed:11517336).
Interacts with PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1. Interacts with NOX4 (By similarity).
Interacts with EIF2S1 (By similarity).
Interacts with PCNA (PubMed:9371605).
Interacts with LYN and KMT2A/MLL1 (PubMed:11517336).
Interacts with PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1. Interacts with NOX4 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-60 | Required for localization in the endoplasmic reticulum | ||||
Sequence: MAPSPRPQHVLHWRDAHNFYLLSPLMGLLSRAWSRLRGPEVPEAWLAKTVTGADQIEAAA | ||||||
Region | 65-89 | Disordered | ||||
Sequence: TPVSGNLLPHGETEESGSPEQSQAA | ||||||
Region | 101-123 | Disordered | ||||
Sequence: PPETWGLSNVDEYNAKPGQDDLR | ||||||
Region | 156-278 | Disordered | ||||
Sequence: EGVAEPAYPTSQLEGGPAENEEDGETVKTYQASAASIAPGYKPSTPVPFLGEAEHQATEEKGTENKADPSNSPSSGSHSRAWEYYSREKPKQEGEAKVEAHRAGQGHPCRNAEAEEGGPETTF | ||||||
Compositional bias | 222-236 | Polar residues | ||||
Sequence: ADPSNSPSSGSHSRA | ||||||
Compositional bias | 237-264 | Basic and acidic residues | ||||
Sequence: WEYYSREKPKQEGEAKVEAHRAGQGHPC | ||||||
Repeat | 283-322 | 1 | ||||
Sequence: NAFLKAWVYRPGEDTEEEDNSDSDSAEEDTAQTGATPHTS | ||||||
Region | 283-451 | 4.5 X approximate repeats | ||||
Sequence: NAFLKAWVYRPGEDTEEEDNSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSPFLKAWVYRPGEDTE | ||||||
Region | 291-496 | Disordered | ||||
Sequence: YRPGEDTEEEDNSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSPFLKAWVYRPGEDTEDDTEEEEDSENVAPGDSETADSSQSPCLQPQRCLPGEKTKGRGEE | ||||||
Repeat | 323-360 | 2 | ||||
Sequence: AFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTS | ||||||
Region | 323-503 | Interaction with SMAD7 | ||||
Sequence: AFLKAWVYRPGEDTEEEDSDSDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSAFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTSPFLKAWVYRPGEDTEDDTEEEEDSENVAPGDSETADSSQSPCLQPQRCLPGEKTKGRGEEPPLFQVA | ||||||
Repeat | 361-398 | 3 | ||||
Sequence: AFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTS | ||||||
Repeat | 399-436 | 4 | ||||
Sequence: AFLKAWVYRPGEDTEEENSDLDSAEEDTAQTGATPHTS | ||||||
Repeat | 437-451 | 5; truncated | ||||
Sequence: PFLKAWVYRPGEDTE | ||||||
Region | 443-548 | Interaction with KMT2A/MLL1 | ||||
Sequence: VYRPGEDTEDDTEEEEDSENVAPGDSETADSSQSPCLQPQRCLPGEKTKGRGEEPPLFQVAFYLPGEKPESPWAAPKLPLRLQRRLRLFKAPTRDQDPEIPLKARK | ||||||
Compositional bias | 449-465 | Acidic residues | ||||
Sequence: DTEDDTEEEEDSENVAP | ||||||
Compositional bias | 466-481 | Polar residues | ||||
Sequence: GDSETADSSQSPCLQP | ||||||
Region | 529-576 | Interaction with SMARCB1 | ||||
Sequence: RLFKAPTRDQDPEIPLKARKVHFAEKVTVHFLAVWAGPAQAARRGPWE | ||||||
Region | 610-657 | Disordered | ||||
Sequence: ARLRNPSLPQSEPRSSSEATPLTQDVTTPSPLPSETPSPSLYLGGRRG | ||||||
Compositional bias | 617-640 | Polar residues | ||||
Sequence: LPQSEPRSSSEATPLTQDVTTPSP |
Sequence similarities
Belongs to the PPP1R15 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P17564-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length657
- Mass (Da)71,840
- Last updated1990-08-01 v1
- Checksum9B217001019C38A7
P17564-2
- Name2
- Differences from canonical
- 284-360: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1B0GRX4 | A0A1B0GRX4_MOUSE | Ppp1r15a | 103 |
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 222-236 | Polar residues | ||||
Sequence: ADPSNSPSSGSHSRA | ||||||
Sequence conflict | 224 | in Ref. 2; BAE39419 | ||||
Sequence: P → H | ||||||
Compositional bias | 237-264 | Basic and acidic residues | ||||
Sequence: WEYYSREKPKQEGEAKVEAHRAGQGHPC | ||||||
Sequence conflict | 271 | in Ref. 2; BAE32770 | ||||
Sequence: E → G | ||||||
Alternative sequence | VSP_031651 | 284-360 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 449-465 | Acidic residues | ||||
Sequence: DTEDDTEEEEDSENVAP | ||||||
Compositional bias | 466-481 | Polar residues | ||||
Sequence: GDSETADSSQSPCLQP | ||||||
Sequence conflict | 505 | in Ref. 2; BAE32770 | ||||
Sequence: Y → C | ||||||
Compositional bias | 617-640 | Polar residues | ||||
Sequence: LPQSEPRSSSEATPLTQDVTTPSP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X51829 EMBL· GenBank· DDBJ | CAA36128.1 EMBL· GenBank· DDBJ | mRNA | ||
AK079339 EMBL· GenBank· DDBJ | BAC37613.1 EMBL· GenBank· DDBJ | mRNA | ||
AK154697 EMBL· GenBank· DDBJ | BAE32770.1 EMBL· GenBank· DDBJ | mRNA | ||
AK167317 EMBL· GenBank· DDBJ | BAE39419.1 EMBL· GenBank· DDBJ | mRNA |