P36873 · PP1G_HUMAN
- ProteinSerine/threonine-protein phosphatase PP1-gamma catalytic subunit
- GenePPP1CC
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids323 (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. Dephosphorylates RPS6KB1 (PubMed:17936702).
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 (PubMed:20516061).
In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997).
May dephosphorylate CSNK1D and CSNK1E (By similarity).
Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702).
Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
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 (PubMed:20516061).
In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997).
May dephosphorylate CSNK1D and CSNK1E (By similarity).
Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702).
Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
Miscellaneous
Microcystin toxin is bound to Cys-273 through a thioether bond.
Catalytic activity
- H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate
Cofactor
Note: Binds 2 manganese ions per subunit.
Activity regulation
Inactivated by binding to URI1. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.
Features
Showing features for binding site, active site, 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 | ||||||
Site | 273 | Inhibition by microcystin toxin binding | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein phosphatase PP1-gamma catalytic subunit
- EC number
- Short namesPP-1G
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP36873
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with SPZ1 in the nucleus (By similarity).
Colocalizes with URI1 at mitochondrion (PubMed:17936702).
Rapidly exchanges between the nucleolar, nucleoplasmic and cytoplasmic compartments (PubMed:11739654).
Highly mobile in cells and can be relocalized through interaction with targeting subunits (PubMed:17965019).
In the presence of PPP1R8 relocalizes from the nucleolus to nuclear speckles (PubMed:11739654).
Shows a dynamic targeting to specific sites throughout the cell cycle (PubMed:12529430).
Highly concentrated in nucleoli of interphase cells and localizes at kinetochores early in mitosis (PubMed:12529430).
Relocalization to chromosome-containing regions occurs at the transition from early to late anaphase (PubMed:12529430).
Also accumulates at the cleavage furrow and midbody by telophase (PubMed:12529430).
Colocalizes with DYNLT4 in the microtubule organizing center (MTOC) (PubMed:23789093).
Colocalizes with URI1 at mitochondrion (PubMed:17936702).
Rapidly exchanges between the nucleolar, nucleoplasmic and cytoplasmic compartments (PubMed:11739654).
Highly mobile in cells and can be relocalized through interaction with targeting subunits (PubMed:17965019).
In the presence of PPP1R8 relocalizes from the nucleolus to nuclear speckles (PubMed:11739654).
Shows a dynamic targeting to specific sites throughout the cell cycle (PubMed:12529430).
Highly concentrated in nucleoli of interphase cells and localizes at kinetochores early in mitosis (PubMed:12529430).
Relocalization to chromosome-containing regions occurs at the transition from early to late anaphase (PubMed:12529430).
Also accumulates at the cleavage furrow and midbody by telophase (PubMed:12529430).
Colocalizes with DYNLT4 in the microtubule organizing center (MTOC) (PubMed:23789093).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 125 | Loss of activity. | ||||
Sequence: H → A | ||||||
Natural variant | VAR_051734 | 152 | in dbSNP:rs11558237 | |||
Sequence: F → S | ||||||
Mutagenesis | 273 | Abolishes interaction with microcystin toxin. | ||||
Sequence: C → A, S, or L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 211 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000058787 | 2-323 | UniProt | Serine/threonine-protein phosphatase PP1-gamma catalytic subunit | |||
Sequence: ADLDKLNIDSIIQRLLEVRGSKPGKNVQLQENEIRGLCLKSREIFLSQPILLELEAPLKICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFLLRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDLQSMEQIRRIMRPTDVPDQGLLCDLLWSDPDKDVLGWGENDRGVSFTFGAEVVAKFLHKHDLDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGAMMSVDETLMCSFQILKPAEKKKPNATRPVTPPRGMITKQAKK | |||||||
Modified residue (large scale data) | 48 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 129 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 177 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 182 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 307 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 311 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 311 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylated by NEK2.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.
Gene expression databases
Organism-specific 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 cyanobacterial toxin microcystin; disulfide-linked. Interacts with PPP1R3B and PPP1R7. Isoform 2 interacts with SPZ1 (By similarity).
Interacts with CDCA2. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with PPP1R42; the interaction is direct (By similarity).
Interacts with NOM1 and PPP1R8. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with isoform 1 and isoform 4 NEK2. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts with FOXP3. Interacts with TMEM225 (via RVxF motif) (By similarity).
Interacts with MKI67 (PubMed:24867636).
Interacts with RRP1B; this targets PPP1CC to the nucleolus (PubMed:20926688).
Interacts with PPP1R2B (PubMed:23506001).
Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).
Interacts with DYNLT4 (PubMed:23789093).
Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity (PubMed:34260926).
Interacts with CDCA2. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with PPP1R42; the interaction is direct (By similarity).
Interacts with NOM1 and PPP1R8. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with isoform 1 and isoform 4 NEK2. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts with FOXP3. Interacts with TMEM225 (via RVxF motif) (By similarity).
Interacts with MKI67 (PubMed:24867636).
Interacts with RRP1B; this targets PPP1CC to the nucleolus (PubMed:20926688).
Interacts with PPP1R2B (PubMed:23506001).
Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).
Interacts with DYNLT4 (PubMed:23789093).
Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity (PubMed:34260926).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 302-323 | Disordered | ||||
Sequence: KKPNATRPVTPPRGMITKQAKK |
Sequence similarities
Belongs to the PPP phosphatase family. PP-1 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P36873-1
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
- SynonymsPPPCC1, Gamma-1
- Length323
- Mass (Da)36,984
- Last updated1994-06-01 v1
- Checksum0EEEF0E842188536
P36873-2
- Name2
- SynonymsPPPCC2, Gamma-2
- Differences from canonical
- 315-323: GMITKQAKK → VASGLNPSIQKASNYRNNTVLYE
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_005094 | 315-323 | in isoform 2 | |||
Sequence: GMITKQAKK → VASGLNPSIQKASNYRNNTVLYE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X74008 EMBL· GenBank· DDBJ | CAA52169.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014073 EMBL· GenBank· DDBJ | AAH14073.1 EMBL· GenBank· DDBJ | mRNA | ||
L07395 EMBL· GenBank· DDBJ | AAA19823.1 EMBL· GenBank· DDBJ | mRNA |