PPP1CA
entrez
5499
canonical
uniprot
P62136
canonical
ensembl
ENSG00000172531
resolver
ensp
ENSP00000326031
resolver
ensp
ENSP00000350974
resolver
ensp
ENSP00000365936
resolver
genesymbol
PPP1CA
resolver
genesymbol_syn
PPP1A
resolver
hgnc
HGNC:9281
resolver
uniprot
A0A140VJS9
resolver
uniprot
A6NNR3
resolver
uniprot
B2R908
resolver
uniprot
P08129
resolver
uniprot
P20653
resolver
uniprot
P22802
resolver
uniprot
Q07161
resolver
uniprot_entry
A0A140VJS9_HUMAN
resolver
uniprot_entry
PP1A_HUMAN
resolver
uniprot_sec
A6NNR3
resolver
uniprot_sec
B2R908
resolver
uniprot_sec
P08129
resolver
uniprot_sec
P20653
resolver
uniprot_sec
P22802
resolver
uniprot_sec
Q07161
resolver
activity_regulation
ACTIVITY REGULATION: The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress. {ECO:0000269|PubMed:15705855}.
uniprot
proteins
amino_acid_sequence
MSDSEKLNLDSIIGRLLEVQGSRPGKNVQLTENEIRGLCLKSREIFLSQPILLELEAPLKICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFLLRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDLQSMEQIRRIMRPTDVPDQGLLCDLLWSDPDKDVQGWGENDRGVSFTFGAEVVAKFLHKHDLDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGAMMSVDETLMCSFQILKPADKNKGKYGQFSGLNPGGRPITPPRNSAKAKK
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
function
FUNCTION: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets (PubMed:28216226, PubMed:30158517, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). Protein phosphatase 1 (PP1) is essential for cell division, transcription elongation, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). 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 Ca(2+)/calmodulin dependent protein kinase II. Catalytic component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation: the PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex also regulates transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription (PubMed:31677974). PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at 'Ser-5' of the CTD, promoting RNA polymerase II degradation (PubMed:33264625). PNUTS-PP1 also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (PubMed:20516061). Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage (PubMed:17283141). Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development (By similarity). 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 (PubMed:21712997). 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). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323). Together with PPP1CC (PP1-gamma subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response (PubMed:23499489). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000250|UniProtKB:P62137, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:30158517, ECO:0000269|PubMed:31677974, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670, ECO:0000269|PubMed:39603239, ECO:0000269|PubMed:39603240}.; FUNCTION: (Microbial infection) Necessary for alphaviruses replication. {ECO:0000269|PubMed:29769351}.
uniprot
proteins
mass_dalton
37512
uniprot
proteins
mutagenesis
MUTAGEN 50; /note="P->R: Promotes SMP complex formation."; /evidence="ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670"; MUTAGEN 57; /note="A->P: No effect on SMP complex formation."; /evidence="ECO:0000269|PubMed:36175670"; MUTAGEN 184; /note="E->A: Promotes SMP complex formation."; /evidence="ECO:0000269|PubMed:36175670"; MUTAGEN 188; /note="R->A: Abolishes SMP complex formation."; /evidence="ECO:0000269|PubMed:36175670
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation. {ECO:0000269|PubMed:16732323}.
uniprot
proteins
protein_family
PP-1 subfamily
uniprot
proteins
protein_family
PPP phosphatase family
uniprot
proteins
pubmed
11564868
uniprot
proteins
pubmed
11739654
uniprot
proteins
pubmed
11839776
uniprot
proteins
pubmed
12226088
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15705855
uniprot
proteins
pubmed
16263087
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16732323
uniprot
proteins
pubmed
17283141
uniprot
proteins
pubmed
17626005
uniprot
proteins
pubmed
17890166
uniprot
proteins
pubmed
17965019
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18992256
uniprot
proteins
pubmed
19377461
uniprot
proteins
pubmed
19389623
uniprot
proteins
pubmed
19581931
uniprot
proteins
pubmed
19826001
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20305656
uniprot
proteins
pubmed
20424263
uniprot
proteins
pubmed
20516061
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
2161401
uniprot
proteins
pubmed
21712997
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23213405
uniprot
proteins
pubmed
23396208
uniprot
proteins
pubmed
23499489
uniprot
proteins
pubmed
23846654
uniprot
proteins
pubmed
24336203
uniprot
proteins
pubmed
24591642
uniprot
proteins
pubmed
25556658
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26083323
uniprot
proteins
pubmed
26095357
uniprot
proteins
pubmed
26981768
uniprot
proteins
pubmed
28216226
uniprot
proteins
pubmed
29769351
uniprot
proteins
pubmed
30100357
uniprot
proteins
pubmed
30158517
uniprot
proteins
pubmed
31677974
uniprot
proteins
pubmed
33264625
uniprot
proteins
pubmed
35768504
uniprot
proteins
pubmed
35830882
uniprot
proteins
pubmed
35831509
uniprot
proteins
pubmed
36175670
uniprot
proteins
pubmed
39256359
uniprot
proteins
pubmed
39446389
uniprot
proteins
pubmed
39603239
uniprot
proteins
pubmed
39603240
uniprot
proteins
pubmed
8384581
uniprot
proteins
pubmed
8392016
uniprot
proteins
pubmed
9023344
uniprot
proteins
sequence_length
330
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:29769351}. Nucleus {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:17965019}. Nucleus, nucleoplasm {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:17965019}. Nucleus, nucleolus {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:17965019}. Postsynaptic density {ECO:0000250|UniProtKB:P62137}. 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. Shuttles toward the cytosol during infection with VEEV (PubMed:29769351). {ECO:0000269|PubMed:29769351}.
uniprot
proteins