Enzyme found in humans
Nuclear inhibitor of protein phosphatase 1 is an enzyme that in humans is encoded by the PPP1R8 gene .[ 5] [ 6] [ 7]
This gene, through alternative splicing, encodes three different isoforms . Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA.[ 7]
Interactions PPP1R8 has been shown to interact with PPP1CA ,[ 8] [ 9] Histone deacetylase 2 ,[ 8] SF3B1 [ 10] EED [ 8] PRC2 .[ 11]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000117751 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028882 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Wang M, Cohen SN (November 1994). "ard-1: a human gene that reverses the effects of temperature-sensitive and deletion mutations in the Escherichia coli rne gene and encodes an activity producing RNase E-like cleavages" . Proc Natl Acad Sci USA . 91 (22): 10591–5. Bibcode :1994PNAS...9110591W . doi :10.1073/pnas.91.22.10591 PMC 45067 PMID 7524097 . ^ Mishima K, Tsuchiya M, Nightingale MS, Moss J, Vaughan M (May 1993). "ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain" . J Biol Chem . 268 (12): 8801–7. doi :10.1016/S0021-9258(18)52945-8 PMID 8473324 . ^ a b "Entrez Gene: PPP1R8 protein phosphatase 1, regulatory (inhibitor) subunit 8" .^ a b c Jin Q, van Eynde Aleyde, Beullens Monique, Roy Nivedita, Thiel Gerald, Stalmans Willy, Bollen Mathieu (August 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 . 278 (33): 30677–85. doi :10.1074/jbc.M302273200 ISSN 0021-9258 . PMID 12788942 . ^ Ajuh PM, Browne G J, Hawkes N A, Cohen P T, Roberts S G, Lamond A I (February 2000). "Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex" . Nucleic Acids Res . 28 (3): 678–86. doi :10.1093/nar/28.3.678 . PMC 102561 PMID 10637318 . ^ Boudrez A, Beullens Monique, Waelkens Etienne, Stalmans Willy, Bollen Mathieu (August 2002). "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1" . J. Biol. Chem . 277 (35): 31834–41. doi :10.1074/jbc.M204427200 ISSN 0021-9258 . PMID 12105215 . ^ Ferreira M, Verbinnen I, Fardilha M, Van Eynde A, Bollen M (November 2018). "The deletion of the protein phosphatase 1 regulator NIPP1 in testis causes hyperphosphorylation and degradation of the histone methyltransferase EZH2" . J. Biol. Chem . 293 (47): 18031–18039. doi :10.1074/jbc.AC118.005577 PMC 6254331 PMID 30305391 .
Further reading
Van Eynde A, Wera S, Beullens M, et al. (1996). "Molecular cloning of NIPP-1, a nuclear inhibitor of protein phosphatase-1, reveals homology with polypeptides involved in RNA processing" . J. Biol. Chem . 270 (47): 28068–74. doi :10.1074/jbc.270.47.28068 PMID 7499293 . Claverie-Martin F, Wang M, Cohen SN (1997). "ARD-1 cDNA from human cells encodes a site-specific single-strand endoribonuclease that functionally resembles Escherichia coli RNase E." J. Biol. Chem . 272 (21): 13823–8. doi :10.1074/jbc.272.21.13823 PMID 9153239 . Vulsteke V, Beullens M, Waelkens E, et al. (1998). "Properties and phosphorylation sites of baculovirus-expressed nuclear inhibitor of protein phosphatase-1 (NIPP-1)" . J. Biol. Chem . 272 (52): 32972–8. doi :10.1074/jbc.272.52.32972 PMID 9407077 . Van Eynde A, Pérez-Callejón E, Schoenmakers E, et al. (1999). "Organization and alternate splice products of the gene encoding nuclear inhibitor of protein phosphatase-1 (NIPP-1)" . Eur. J. Biochem . 261 (1): 291–300. doi :10.1046/j.1432-1327.1999.00272.x PMID 10103062 . Jin Q, Beullens M, Jagiello I, et al. (1999). "Mapping of the RNA-binding and endoribonuclease domains of NIPP1, a nuclear targeting subunit of protein phosphatase 1" . Biochem. J . 342. ( Pt 1) (1): 13–9. doi :10.1042/0264-6021:3420013 . PMC 1220430 PMID 10432294 . Chang AC, Sohlberg B, Trinkle-Mulcahy L, et al. (2000). "Alternative splicing regulates the production of ARD-1 endoribonuclease and NIPP-1, an inhibitor of protein phosphatase-1, as isoforms encoded by the same gene" . Gene . 240 (1): 45–55. doi :10.1016/S0378-1119(99)00435-7 PMID 10564811 . 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 . Jagiello I, Van Eynde A, Vulsteke V, et al. (2001). "Nuclear and subnuclear targeting sequences of the protein phosphatase-1 regulator NIPP1". J. Cell Sci . 113. Pt 21 (21): 3761–8. doi :10.1242/jcs.113.21.3761 . PMID 11034904 . Beullens M, Vulsteke V, Van Eynde A, et al. (2001). "The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding" . Biochem. J . 352. Pt 3 (Pt 3): 651–8. PMC 1221501 PMID 11104670 . Trinkle-Mulcahy L, Sleeman JE, Lamond AI (2002). "Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells" . J. Cell Sci . 114 (Pt 23): 4219–28. doi :10.1242/jcs.114.23.4219 . PMID 11739654 . Beullens M, Bollen M (2002). "The protein phosphatase-1 regulator NIPP1 is also a splicing factor involved in a late step of spliceosome assembly" . J. Biol. Chem . 277 (22): 19855–60. doi :10.1074/jbc.M200847200 PMID 11909864 . Boudrez A, Beullens M, Waelkens E, et al. (2002). "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1" . J. Biol. Chem . 277 (35): 31834–41. doi :10.1074/jbc.M204427200 PMID 12105215 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Ammosova T, Jerebtsova M, Beullens M, et al. (2003). "Nuclear protein phosphatase-1 regulates HIV-1 transcription" . J. Biol. Chem . 278 (34): 32189–94. doi :10.1074/jbc.M300521200 PMID 12788939 . Jin Q, van Eynde A, Beullens M, et al. (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 . 278 (33): 30677–85. doi :10.1074/jbc.M302273200 PMID 12788942 . Vulsteke V, Beullens M, Boudrez A, et al. (2004). "Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1" . J. Biol. Chem . 279 (10): 8642–7. doi :10.1074/jbc.M311466200 PMID 14699119 . Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway" . Genome Res . 14 (7): 1324–32. doi :10.1101/gr.2334104 . PMC 442148 PMID 15231748 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 .
