P62137 · PP1A_MOUSE
- ProteinSerine/threonine-protein phosphatase PP1-alpha catalytic subunit
- GenePpp1ca
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids330 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca2+/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates CENPA (By similarity).
Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).
Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).
Catalytic activity
- H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 Fe cation per subunit.
Note: Binds 2 manganese ions per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 64 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 66 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 92 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 92 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 124 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 125 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 173 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 248 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein phosphatase PP1-alpha catalytic subunit
- EC number
- Short namesPP-1A
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 accessionP62137
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Primarily nuclear and largely excluded from the nucleolus. Highly mobile in cells and can be relocalized through interaction with targeting subunits. NOM1 plays a role in targeting this protein to the nucleolus. In the presence of PPP1R8 relocalizes from the nucleus to nuclear speckles (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 64 | Dominant negative, severely disrupts circadian rhythmicity of transcription. | ||||
Sequence: D → N | ||||||
Mutagenesis | 95 | Dominant negative, severely disrupts circadian rhythmicity of transcription. | ||||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Modified residue | 2 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000058775 | 2-330 | Serine/threonine-protein phosphatase PP1-alpha catalytic subunit | |||
Sequence: SDSEKLNLDSIIGRLLEVQGSRPGKNVQLTENEIRGLCLKSREIFLSQPILLELEAPLKICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIRYPENFFLLRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDLQSMEQIRRIMRPTDVPDQGLLCDLLWSDPDKDVQGWGENDRGVSFTFGAEVVAKFLHKHDLDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGAMMSVDETLMCSFQILKPADKNKGKYGQFSGLNPGGRPITPPRNSAKAKK | ||||||
Modified residue | 22 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 305 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 306 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 320 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 325 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R9A, PPP1R9B and PPP1R7. Interacts with PPP1R15A; the interaction mediates binding to EIF2S1. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts. with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with PPP1R39. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site (By similarity).
Interacts with PPP1R15B; the interaction mediates binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with NEK2. Interacts with FER; this promotes phosphorylation at Thr-320 (By similarity).
Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with BTBD10 (PubMed:18160256).
Interacts with KCTD20 (PubMed:24156551).
Interacts with FOXP3 (By similarity).
Interacts with CENPA (By similarity).
Interacts with ATG16L1 (By similarity).
Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity).
Interacts with tensin TNS1 (By similarity).
Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2 (By similarity).
Interacts with TPRN; the interaction results in inhibition of PPC1A phosphatase activity (By similarity).
Interacts with SKA1 (via C-terminus); the interaction is direct and required for the recruitment of PP1 to the kinetochore (By similarity).
Interacts with PPP1R15B; the interaction mediates binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with NEK2. Interacts with FER; this promotes phosphorylation at Thr-320 (By similarity).
Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with BTBD10 (PubMed:18160256).
Interacts with KCTD20 (PubMed:24156551).
Interacts with FOXP3 (By similarity).
Interacts with CENPA (By similarity).
Interacts with ATG16L1 (By similarity).
Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity).
Interacts with tensin TNS1 (By similarity).
Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2 (By similarity).
Interacts with TPRN; the interaction results in inhibition of PPC1A phosphatase activity (By similarity).
Interacts with SKA1 (via C-terminus); the interaction is direct and required for the recruitment of PP1 to the kinetochore (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P62137 | Axin1 O35625 | 2 | EBI-357187, EBI-2365912 | |
BINARY | P62137 | Bmal1 Q9WTL8 | 2 | EBI-357187, EBI-644534 | |
BINARY | P62137 | Id2 P41136 | 2 | EBI-357187, EBI-309167 | |
BINARY | P62137 | Pcna P17918 | 2 | EBI-357187, EBI-1173716 | |
BINARY | P62137 | Ppp1r7 Q3UM45 | 3 | EBI-357187, EBI-8318179 | |
BINARY | P62137 | Skp1 Q9WTX5 | 2 | EBI-357187, EBI-1202363 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 306-330 | Disordered | ||||
Sequence: YGQFSGLNPGGRPITPPRNSAKAKK |
Sequence similarities
Belongs to the PPP phosphatase family. PP-1 subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length330
- Mass (Da)37,540
- Last updated2004-06-21 v1
- Checksum8FBFD158A52282E0
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U25809 EMBL· GenBank· DDBJ | AAC99814.1 EMBL· GenBank· DDBJ | mRNA | ||
AK007932 EMBL· GenBank· DDBJ | BAB25358.1 EMBL· GenBank· DDBJ | mRNA | ||
AK028392 EMBL· GenBank· DDBJ | BAC25928.1 EMBL· GenBank· DDBJ | mRNA | ||
AK090070 EMBL· GenBank· DDBJ | BAC41078.1 EMBL· GenBank· DDBJ | mRNA | ||
AK151582 EMBL· GenBank· DDBJ | BAE30522.1 EMBL· GenBank· DDBJ | mRNA | ||
AK152667 EMBL· GenBank· DDBJ | BAE31402.1 EMBL· GenBank· DDBJ | mRNA | ||
AK153517 EMBL· GenBank· DDBJ | BAE32060.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159575 EMBL· GenBank· DDBJ | BAE35196.1 EMBL· GenBank· DDBJ | mRNA | ||
AK167244 EMBL· GenBank· DDBJ | BAE39365.1 EMBL· GenBank· DDBJ | mRNA | ||
AK167538 EMBL· GenBank· DDBJ | BAE39605.1 EMBL· GenBank· DDBJ | mRNA | ||
AK167880 EMBL· GenBank· DDBJ | BAE39893.1 EMBL· GenBank· DDBJ | mRNA | ||
AK167981 EMBL· GenBank· DDBJ | BAE39973.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014828 EMBL· GenBank· DDBJ | AAH14828.1 EMBL· GenBank· DDBJ | mRNA |