Search Results
Overview
| Uniprot ID | P62136 |
|---|---|
| Protein Name | Serine/threonine-protein phosphatase PP1-alpha catalytic subunit |
| Gene Name | PPP1CA |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 141 | YGFYDECKRRYNIKL |
| 26 | VQGSRPGKNVQLTEN |
| 305 | PADKNKGKYGQFSGL |
| 41 | EIRGLCLKSREIFLS |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005912 | adherens junction |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0043197 | dendritic spine |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0098978 | glutamatergic synapse |
| Cellular Component | GO:0042587 | glycogen granule |
| Cellular Component | GO:0005730 | nucleolus |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0043204 | perikaryon |
| Cellular Component | GO:0098793 | presynapse |
| Cellular Component | GO:0000164 | protein phosphatase type 1 complex |
| Cellular Component | GO:0072357 | PTW/PP1 phosphatase complex |
| Molecular Function | GO:0098641 | cadherin binding involved in cell-cell adhesion |
| Molecular Function | GO:0005506 | iron ion binding |
| Molecular Function | GO:0016791 | phosphatase activity |
| Molecular Function | GO:0004721 | phosphoprotein phosphatase activity |
| Molecular Function | GO:0008157 | protein phosphatase 1 binding |
| Molecular Function | GO:0004722 | protein serine/threonine phosphatase activity |
| Molecular Function | GO:0043021 | ribonucleoprotein complex binding |
| Molecular Function | GO:0180007 | RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity |
| Molecular Function | GO:0046914 | transition metal ion binding |
| Biological Process | GO:0051301 | cell division |
| Biological Process | GO:0032922 | circadian regulation of gene expression |
| Biological Process | GO:0043153 | entrainment of circadian clock by photoperiod |
| Biological Process | GO:0005977 | glycogen metabolic process |
| Biological Process | GO:0034244 | negative regulation of transcription elongation by RNA polymerase II |
| Biological Process | GO:0045725 | positive regulation of glycogen biosynthetic process |
| Biological Process | GO:0046579 | positive regulation of Ras protein signal transduction |
| Biological Process | GO:2000806 | positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled |
| Biological Process | GO:0032968 | positive regulation of transcription elongation by RNA polymerase II |
| Biological Process | GO:0006470 | protein dephosphorylation |
| Biological Process | GO:0050821 | protein stabilization |
| Biological Process | GO:0060828 | regulation of canonical Wnt signaling pathway |
| Biological Process | GO:0042752 | regulation of circadian rhythm |
| Biological Process | GO:0005981 | regulation of glycogen catabolic process |
| Biological Process | GO:0043558 | regulation of translational initiation in response to stress |
| Biological Process | GO:0010288 | response to lead ion |
| Biological Process | GO:0001111 | RNA polymerase II promoter clearance |
| Biological Process | GO:0043247 | telomere maintenance in response to DNA damage |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.