PPP1R8

Nuclear inhibitor of protein phosphatase 1 is an enzyme that in humans is encoded by the PPP1R8 gene.[5][6][7]

PPP1R8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3V4Y
Identifiers
Aliases	PPP1R8, ARD-1, ARD1, NIPP-1, NIPP1, PRO2047, protein phosphatase 1 regulatory subunit 8
External IDs	OMIM: 602636 MGI: 2140494 HomoloGene: 8555 GeneCards: PPP1R8
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p35.3 Start 27,830,782 bp[1] End 27,851,676 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.3 Start 132,826,929 bp[2] End 132,843,169 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein serine/threonine phosphatase inhibitor activity • DNA binding • GO:0001948 protein binding • RNA binding • protein phosphatase inhibitor activity • nuclease activity • endonuclease activity • ribonuclease E activity • hydrolase activity • mRNA binding • protein phosphatase regulator activity Cellular component • cytoplasm • nuclear speck • nucleoplasm • spliceosomal complex • cell nucleus Biological process • regulation of transcription, DNA-templated • nucleic acid phosphodiester bond hydrolysis • mRNA processing • RNA catabolic process • transcription, DNA-templated • RNA splicing • cellular proliferation • RNA phosphodiester bond hydrolysis • negative regulation of protein dephosphorylation • negative regulation of phosphoprotein phosphatase activity • regulation of phosphoprotein phosphatase activity • production of miRNAs involved in gene silencing by miRNA Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5511	100336
Ensembl	ENSG00000117751	ENSMUSG00000028882
UniProt	Q12972	Q8R3G1
RefSeq (mRNA)	NM_138558 NM_002713 NM_014110	NM_001290725 NM_146154 NM_001355198 NM_001355199
RefSeq (protein)	NP_002704 NP_054829 NP_612568	NP_001277654 NP_666266 NP_001342127 NP_001342128
Location (UCSC)	Chr 1: 27.83 – 27.85 Mb	Chr 4: 132.83 – 132.84 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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] and the EZH2 domain of PRC2.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000117751 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028882 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. PMID 8473324.
7. "Entrez Gene: PPP1R8 protein phosphatase 1, regulatory (inhibitor) subunit 8".
8. Jin, Qiming; 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.
9. Ajuh, P M; 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.
10. Boudrez, An; 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.
11. 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: 3761–8. 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: 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. 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.