PPP1CA
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the PPP1CA gene.
The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies in both human and mice suggest that PP1 is an important regulator of cardiac function. Mouse studies also suggest that PP1 functions as a suppressor of learning and memory. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene.[1]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [2]
Nicotine Activity on Dopaminergic Neurons
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Interactions
PPP1CA has been shown to interact with LMTK2,[3] PPP1R15A,[4][5][6] AKAP11,[7][8] Host cell factor C1,[9] PHACTR3,[10] Protein kinase R,[11] BCL2-like 1,[12] BCL2L2,[12] CDC5L,[13] PPP1R8,[9][14] SMARCB1,[5] KvLQT1,[15] BRCA1[16] and PPP1R9B.[17]
References
- ^ "Entrez Gene: PPP1CA protein phosphatase 1, catalytic subunit, alpha isoform". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5499.
- ^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602.
- ^ Wang, Hong; Brautigan David L (Dec. 2002). "A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2". J. Biol. Chem. (United States) 277 (51): 49605–12. doi:10.1074/jbc.M209335200. ISSN 0021-9258. PMID 12393858.
- ^ Hung, Wesley J; Roberson Rachel S, Taft Jaime, Wu Daniel Y (May. 2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. (United States) 23 (10): 3477–86. doi:10.1128/MCB.23.10.3477-3486.2003. ISSN 0270-7306. PMC 164759. PMID 12724406. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=164759.
- ^ a b Wu, Daniel Y; Tkachuck Douglas C, Roberson Rachel S, Schubach William H (Aug. 2002). "The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity". J. Biol. Chem. (United States) 277 (31): 27706–15. doi:10.1074/jbc.M200955200. ISSN 0021-9258. PMID 12016208.
- ^ Connor, J H; Weiser D C, Li S, Hallenbeck J M, Shenolikar S (Oct. 2001). "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1". Mol. Cell. Biol. (United States) 21 (20): 6841–50. doi:10.1128/MCB.21.20.6841-6850.2001. ISSN 0270-7306. PMC 99861. PMID 11564868. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99861.
- ^ Tanji, Chie; Yamamoto Hideki, Yorioka Noriaki, Kohno Nobuoki, Kikuchi Kunimi, Kikuchi Akira (Oct. 2002). "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta". J. Biol. Chem. (United States) 277 (40): 36955–61. doi:10.1074/jbc.M206210200. ISSN 0021-9258. PMID 12147701.
- ^ Schillace, R V; Scott J D (Mar. 1999). "Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220". Curr. Biol. (ENGLAND) 9 (6): 321–4. doi:10.1016/S0960-9822(99)80141-9. ISSN 0960-9822. PMID 10209101.
- ^ a b Ajuh, P M; Browne G J, Hawkes N A, Cohen P T, Roberts S G, Lamond A I (Feb. 2000). "Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex". Nucleic Acids Res. (ENGLAND) 28 (3): 678–86. doi:10.1093/nar/28.3.678. PMC 102561. PMID 10637318. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=102561.
- ^ Sagara, Junji; Higuchi Tsukasa, Hattori Yukiko, Moriya Mie, Sarvotham Haritha, Shima Hiroshi, Shirato Haruki, Kikuchi Kunimi, Taniguchi Shunichiro (Nov. 2003). "Scapinin, a putative protein phosphatase-1 regulatory subunit associated with the nuclear nonchromatin structure". J. Biol. Chem. (United States) 278 (46): 45611–9. doi:10.1074/jbc.M305227200. ISSN 0021-9258. PMID 12925532.
- ^ Tan, Seng-Lai; Tareen Semih U, Melville Mark W, Blakely Collin M, Katze Michael G (Sep. 2002). "The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation". J. Biol. Chem. (United States) 277 (39): 36109–17. doi:10.1074/jbc.M205109200. ISSN 0021-9258. PMID 12138106.
- ^ a b Ayllón, Verónica; Cayla Xavier, García Alphonse, Fleischer Aarne, Rebollo Angelita (Jul. 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. (Germany) 32 (7): 1847–55. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. ISSN 0014-2980. PMID 12115603.
- ^ Ajuh, P; Kuster B, Panov K, Zomerdijk J C, Mann M, Lamond A I (Dec. 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. (ENGLAND) 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305846.
- ^ Jin, Qiming; van Eynde Aleyde, Beullens Monique, Roy Nivedita, Thiel Gerald, Stalmans Willy, Bollen Mathieu (Aug. 2003). "The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor". J. Biol. Chem. (United States) 278 (33): 30677–85. doi:10.1074/jbc.M302273200. ISSN 0021-9258. PMID 12788942.
- ^ Marx, Steven O; Kurokawa Junko, Reiken Steven, Motoike Howard, D'Armiento Jeanine, Marks Andrew R, Kass Robert S (Jan. 2002). "Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel". Science (United States) 295 (5554): 496–9. doi:10.1126/science.1066843. PMID 11799244.
- ^ Liu, Ying; Virshup David M, White Raymond L, Hsu Lih-Ching (Nov. 2002). "Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha". Cancer Res. (United States) 62 (22): 6357–61. ISSN 0008-5472. PMID 12438214.
- ^ Hsieh-Wilson, L C; Allen P B, Watanabe T, Nairn A C, Greengard P (Apr. 1999). "Characterization of the neuronal targeting protein spinophilin and its interactions with protein phosphatase-1". Biochemistry (United States) 38 (14): 4365–73. doi:10.1021/bi982900m. ISSN 0006-2960. PMID 10194355.
Further reading
- Cohen PT (2002). "Protein phosphatase 1--targeted in many directions.". J. Cell. Sci. 115 (Pt 2): 241–56. PMID 11839776.
- Barker HM, Jones TA, da Cruz e Silva EF, et al. (1990). "Localization of the gene encoding a type I protein phosphatase catalytic subunit to human chromosome band 11q13.". Genomics 7 (2): 159–66. doi:10.1016/0888-7543(90)90536-4. PMID 2161401.
- Carrey EA, Campbell DG, Hardie DG (1986). "Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism for regulation of pyrimidine nucleotide biosynthesis.". EMBO J. 4 (13B): 3735–42. PMC 554725. PMID 4092695. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=554725.
- Saadat M, Mizuno Y, Kikuchi K, Yoshida MC (1995). "Comparative mapping of the gene encoding the catalytic subunit of protein phosphatase type 1 alpha (PPP1CA) to human, rat, and mouse chromosomes.". Cytogenet. Cell Genet. 70 (1–2): 55–7. doi:10.1159/000133991. PMID 7736790.
- Durfee T, Becherer K, Chen PL, et al. (1993). "The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit". Genes Dev. 7 (4): 555–69. doi:10.1101/gad.7.4.555. PMID 8384581.
- Song Q, Khanna KK, Lu H, Lavin MF (1993). "Cloning and characterization of a human protein phosphatase 1-encoding cDNA". Gene 129 (2): 291–5. doi:10.1016/0378-1119(93)90282-8. PMID 8392016.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Kwon YG, Huang HB, Desdouits F, et al. (1997). "Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins". Proc. Natl. Acad. Sci. U.S.A. 94 (8): 3536–41. doi:10.1073/pnas.94.8.3536. PMC 20474. PMID 9108011. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20474.
- Colbran RJ, Bass MA, McNeill RB, et al. (1997). "Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory subunits". J. Neurochem. 69 (3): 920–9. doi:10.1046/j.1471-4159.1997.69030920.x. PMID 9282913.
- Allen PB, Kwon YG, Nairn AC, Greengard P (1998). "Isolation and characterization of PNUTS, a putative protein phosphatase 1 nuclear targeting subunit". J. Biol. Chem. 273 (7): 4089–95. doi:10.1074/jbc.273.7.4089. PMID 9461602.
- Zhang J, Zhang L, Zhao S, Lee EY (1998). "Identification and characterization of the human HCG V gene product as a novel inhibitor of protein phosphatase-1". Biochemistry 37 (47): 16728–34. doi:10.1021/bi981169g. PMID 9843442.
- Neumann J, Maas R, Bokník P, et al. (1999). "Pharmacological characterization of protein phosphatase activities in preparations from failing human hearts". J. Pharmacol. Exp. Ther. 289 (1): 188–93. PMID 10087003.
- Schillace RV, Scott JD (1999). "Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220". Curr. Biol. 9 (6): 321–4. doi:10.1016/S0960-9822(99)80141-9. PMID 10209101.
- Takahashi M, Shibata H, Shimakawa M, et al. (1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–74. doi:10.1074/jbc.274.24.17267. PMID 10358086.
- McAvoy T, Allen PB, Obaishi H, et al. (1999). "Regulation of neurabin I interaction with protein phosphatase 1 by phosphorylation". Biochemistry 38 (39): 12943–9. doi:10.1021/bi991227d. PMID 10504266.
- Yoshida K, Watanabe M, Kato H, et al. (1999). "BH-protocadherin-c, a member of the cadherin superfamily, interacts with protein phosphatase 1 alpha through its intracellular domain". FEBS Lett. 460 (1): 93–8. doi:10.1016/S0014-5793(99)01309-5. PMID 10571067.
- Yang J, Hurley TD, DePaoli-Roach AA (2000). "Interaction of inhibitor-2 with the catalytic subunit of type 1 protein phosphatase. Identification of a sequence analogous to the consensus type 1 protein phosphatase-binding motif". J. Biol. Chem. 275 (30): 22635–44. doi:10.1074/jbc.M003082200. PMID 10807923.
- Ayllón V, Martínez-A C, García A, et al. (2000). "Protein phosphatase 1alpha is a Ras-activated Bad phosphatase that regulates interleukin-2 deprivation-induced apoptosis". EMBO J. 19 (10): 2237–46. doi:10.1093/emboj/19.10.2237. PMC 384373. PMID 10811615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=384373.
- Boudrez A, Beullens M, Groenen P, et al. (2000). "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry". J. Biol. Chem. 275 (33): 25411–7. doi:10.1074/jbc.M001676200. PMID 10827081.
- Helps NR, Luo X, Barker HM, Cohen PT (2001). "NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1". Biochem. J. 349 (Pt 2): 509–18. doi:10.1042/0264-6021:3490509. PMC 1221174. PMID 10880350. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221174.
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PDB gallery
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1fjm: PROTEIN SERINE/THREONINE PHOSPHATASE-1 (ALPHA ISOFORM, TYPE I) COMPLEXED WITH MICROCYSTIN-LR TOXIN
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1it6: CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN CALYCULIN A AND THE CATALYTIC SUBUNIT OF PROTEIN PHOSPHATASE 1
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1jk7: CRYSTAL STRUCTURE OF THE TUMOR-PROMOTER OKADAIC ACID BOUND TO PROTEIN PHOSPHATASE-1
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1s70: Complex between protein ser/thr phosphatase-1 (delta) and the myosin phosphatase targeting subunit 1 (MYPT1)
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1u32: Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid
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2bcd: X-ray crystal structure of Protein Phosphatase-1 with the marine toxin motuporin bound
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2bdx: X-ray Crystal Structure of dihydromicrocystin-LA bound to Protein Phosphatase-1
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