true2000-05-302024-03-27213PP1R8_HUMANard-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.Wang M.Cohen S.N.doi:10.1073/pnas.91.22.105911994Proc. Natl. Acad. Sci. U.S.A.9110591-10595NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA)B-cellOrganization and alternate splice products of the gene encoding nuclear inhibitor of protein phosphatase-1 (NIPP-1).Van Eynde A.Perez-Callejon E.Schoenmakers E.Jacquemin M.Stalmans W.Bollen M.doi:10.1046/j.1432-1327.1999.00272.x1999Eur. J. Biochem.261291-300NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA AND BETA)ALTERNATIVE SPLICINGTISSUE SPECIFICITYParathyroidT-cellComplete cDNA sequence of NIPP-1 from human breast cancer cells.Liu J.P.Yang Z.Li H.1999-02EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA)Mammary cancerComplete sequencing and characterization of 21,243 full-length human cDNAs.Ota T.Suzuki Y.Nishikawa T.Otsuki T.Sugiyama T.Irie R.Wakamatsu A.Hayashi K.Sato H.Nagai K.Kimura K.Makita H.Sekine M.Obayashi M.Nishi T.Shibahara T.Tanaka T.Ishii S.Yamamoto J.Saito K.Kawai Y.Isono Y.Nakamura Y.Nagahari K.Murakami K.Yasuda T.Iwayanagi T.Wagatsuma M.Shiratori A.Sudo H.Hosoiri T.Kaku Y.Kodaira H.Kondo H.Sugawara M.Takahashi M.Kanda K.Yokoi T.Furuya T.Kikkawa E.Omura Y.Abe K.Kamihara K.Katsuta N.Sato K.Tanikawa M.Yamazaki M.Ninomiya K.Ishibashi T.Yamashita H.Murakawa K.Fujimori K.Tanai H.Kimata M.Watanabe M.Hiraoka S.Chiba Y.Ishida S.Ono Y.Takiguchi S.Watanabe S.Yosida M.Hotuta T.Kusano J.Kanehori K.Takahashi-Fujii A.Hara H.Tanase T.-O.Nomura Y.Togiya S.Komai F.Hara R.Takeuchi K.Arita M.Imose N.Musashino K.Yuuki H.Oshima A.Sasaki N.Aotsuka S.Yoshikawa Y.Matsunawa H.Ichihara T.Shiohata N.Sano S.Moriya S.Momiyama H.Satoh N.Takami S.Terashima Y.Suzuki O.Nakagawa S.Senoh A.Mizoguchi H.Goto Y.Shimizu F.Wakebe H.Hishigaki H.Watanabe T.Sugiyama A.Takemoto M.Kawakami B.Yamazaki M.'Watanabe K.Kumagai A.Itakura S.Fukuzumi Y.Fujimori Y.Komiyama M.Tashiro H.Tanigami A.Fujiwara T.Ono T.Yamada K.Fujii Y.Ozaki K.Hirao M.Ohmori Y.Kawabata A.Hikiji T.Kobatake N.Inagaki H.Ikema Y.Okamoto S.Okitani R.Kawakami T.Noguchi S.Itoh T.Shigeta K.Senba T.Matsumura K.Nakajima Y.Mizuno T.Morinaga M.Sasaki M.Togashi T.Oyama M.Hata H.Watanabe M.'Komatsu T.Mizushima-Sugano J.Satoh T.Shirai Y.Takahashi Y.Nakagawa K.Okumura K.Nagase T.Nomura N.Kikuchi H.Masuho Y.Yamashita R.Nakai K.Yada T.Nakamura Y.'Ohara O.Isogai T.Sugano S.doi:10.1038/ng12852004Nat. Genet.3640-45NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA)SynoviumThe DNA sequence and biological annotation of human chromosome 1.Gregory S.G.Barlow K.F.McLay K.E.Kaul R.Swarbreck D.Dunham A.Scott C.E.Howe K.L.Woodfine K.Spencer C.C.A.Jones M.C.Gillson C.Searle S.Zhou Y.Kokocinski F.McDonald L.Evans R.Phillips K.Atkinson A.Cooper R.Jones C.Hall R.E.Andrews T.D.Lloyd C.Ainscough R.Almeida J.P.Ambrose K.D.Anderson F.Andrew R.W.Ashwell R.I.S.Aubin K.Babbage A.K.Bagguley C.L.Bailey J.Beasley H.Bethel G.Bird C.P.Bray-Allen S.Brown J.Y.Brown A.J.Buckley D.Burton J.Bye J.Carder C.Chapman J.C.Clark S.Y.Clarke G.Clee C.Cobley V.Collier R.E.Corby N.Coville G.J.Davies J.Deadman R.Dunn M.Earthrowl M.Ellington A.G.Errington H.Frankish A.Frankland J.French L.Garner P.Garnett J.Gay L.Ghori M.R.J.Gibson R.Gilby L.M.Gillett W.Glithero R.J.Grafham D.V.Griffiths C.Griffiths-Jones S.Grocock R.Hammond S.Harrison E.S.I.Hart E.Haugen E.Heath P.D.Holmes S.Holt K.Howden P.J.Hunt A.R.Hunt S.E.Hunter G.Isherwood J.James R.Johnson C.Johnson D.Joy A.Kay M.Kershaw J.K.Kibukawa M.Kimberley A.M.King A.Knights A.J.Lad H.Laird G.Lawlor S.Leongamornlert D.A.Lloyd D.M.Loveland J.Lovell J.Lush M.J.Lyne R.Martin S.Mashreghi-Mohammadi M.Matthews L.Matthews N.S.W.McLaren S.Milne S.Mistry S.Moore M.J.F.Nickerson T.O'Dell C.N.Oliver K.Palmeiri A.Palmer S.A.Parker A.Patel D.Pearce A.V.Peck A.I.Pelan S.Phelps K.Phillimore B.J.Plumb R.Rajan J.Raymond C.Rouse G.Saenphimmachak C.Sehra H.K.Sheridan E.Shownkeen R.Sims S.Skuce C.D.Smith M.Steward C.Subramanian S.Sycamore N.Tracey A.Tromans A.Van Helmond Z.Wall M.Wallis J.M.White S.Whitehead S.L.Wilkinson J.E.Willey D.L.Williams H.Wilming L.Wray P.W.Wu Z.Coulson A.Vaudin M.Sulston J.E.Durbin R.M.Hubbard T.Wooster R.Dunham I.Carter N.P.McVean G.Ross M.T.Harrow J.Olson M.V.Beck S.Rogers J.Bentley D.R.doi:10.1038/nature047272006Nature441315-321NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Mural R.J.Istrail S.Sutton G.G.Florea L.Halpern A.L.Mobarry C.M.Lippert R.Walenz B.Shatkay H.Dew I.Miller J.R.Flanigan M.J.Edwards N.J.Bolanos R.Fasulo D.Halldorsson B.V.Hannenhalli S.Turner R.Yooseph S.Lu F.Nusskern D.R.Shue B.C.Zheng X.H.Zhong F.Delcher A.L.Huson D.H.Kravitz S.A.Mouchard L.Reinert K.Remington K.A.Clark A.G.Waterman M.S.Eichler E.E.Adams M.D.Hunkapiller M.W.Myers E.W.Venter J.C.2005-09EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA)NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-351 (ISOFORM ALPHA)LymphMolecular cloning of NIPP-1, a nuclear inhibitor of protein phosphatase-1, reveals homology with polypeptides involved in RNA processing.Van Eynde A.Wera S.Beullens M.Torrekens S.Van Leuven F.Stalmans W.Bollen M.doi:10.1074/jbc.270.47.280681995J. Biol. Chem.27028068-28074TISSUE SPECIFICITYARD-1 cDNA from human cells encodes a site-specific single-strand endoribonuclease that functionally resembles Escherichia coli RNase E.Claverie-Martin F.Wang M.Cohen S.N.doi:10.1074/jbc.272.21.138231997J. Biol. Chem.27213823-13828CHARACTERIZATION (ISOFORM GAMMA)Mapping of the RNA-binding and endoribonuclease domains of NIPP1, a nuclear targeting subunit of protein phosphatase 1.Jin Q.Beullens M.Jagiello I.Van Eynde A.Vulsteke V.Stalmans W.Bollen M.doi:10.1042/bj34200131999Biochem. J.34213-19RNA-BINDINGCHARACTERIZATION (ISOFORM GAMMA)FUNCTIONAlternative splicing regulates the production of ARD-1 endoribonuclease and NIPP-1, an inhibitor of protein phosphatase-1, as isoforms encoded by the same gene.Chang A.C.Y.Sohlberg B.Trinkle-Mulcahy L.Claverie-Martin F.Cohen P.Cohen S.N.doi:10.1016/s0378-1119(99)00435-71999Gene24045-55IDENTIFICATION OF ALTERNATIVE SPLICING IN ISOFORM GAMMAThe 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.Beullens M.Vulsteke V.Van Eynde A.Jagiello I.Stalmans W.Bollen M.doi:10.1042/bj35206512000Biochem. J.352651-658FUNCTIONMUTAGENESIS OF TYR-264; TYR-335; THR-346 AND SER-348PHOSPHORYLATION AT TYR-264 AND TYR-335NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry.Boudrez A.Beullens M.Groenen P.M.A.Van Eynde A.Vulsteke V.Jagiello I.Murray M.Krainer A.R.Stalmans W.Bollen M.doi:10.1074/jbc.m0016762002000J. Biol. Chem.27525411-25417INTERACTION WITH CDC5LSUBCELLULAR LOCATIONMUTAGENESIS OF 68-SER--HIS-71FUNCTIONNuclear and subnuclear targeting sequences of the protein phosphatase-1 regulator NIPP1.Jagiello I.Van Eynde A.Vulsteke V.Beullens M.Boudrez A.Keppens S.Stalmans W.Bollen M.doi:10.1242/jcs.113.21.37612000J. Cell Sci.1133761-3768NUCLEAR LOCALIZATION SIGNALSMUTAGENESIS OF 68-SER--HIS-71; 195-LYS--LYS-197; SER-199; VAL-201; PHE-203; SER-204 AND 234-LYS--ARG-237SUBCELLULAR LOCATIONDynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells.Trinkle-Mulcahy L.Sleeman J.E.Lamond A.I.doi:10.1242/jcs.114.23.42192001J. Cell Sci.1144219-4228SUBCELLULAR LOCATIONINTERACTION WITH PPP1CA AND PPP1CCMUTAGENESIS OF VAL-201 AND PHE-203The protein phosphatase-1 regulator NIPP1 is also a splicing factor involved in a late step of spliceosome assembly.Beullens M.Bollen M.doi:10.1074/jbc.m2008472002002J. Biol. Chem.27719855-19860IDENTIFICATION AS PART OF THE SPLICEOSOMEFUNCTIONPhosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1.Boudrez A.Beullens M.Waelkens E.Stalmans W.Bollen M.doi:10.1074/jbc.m2044272002002J. Biol. Chem.27731834-31841INTERACTION WITH SF3B1MUTAGENESIS OF 68-SER--HIS-71The 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.Jin Q.van Eynde A.Beullens M.Roy N.Thiel G.Stalmans W.Bollen M.doi:10.1074/jbc.m3022732002003J. Biol. Chem.27830677-30685DNA-BINDINGINTERACTION WITH EEDIDENTIFICATION IN A COMPLEX WITH EED; HDAC2 AND PP1MUTAGENESIS OF 68-SER--HIS-71; 193-LYS--LYS-197; SER-199; VAL-201; PHE-203 AND SER-204FUNCTIONInhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1.Vulsteke V.Beullens M.Boudrez A.Keppens S.Van Eynde A.Rider M.H.Stalmans W.Bollen M.doi:10.1074/jbc.m3114662002004J. Biol. Chem.2798642-8647INTERACTION WITH MELKMUTAGENESIS OF 68-SER--HIS-71A quantitative atlas of mitotic phosphorylation.Dephoure N.Zhou C.Villen J.Beausoleil S.A.Bakalarski C.E.Elledge S.J.Gygi S.P.doi:10.1073/pnas.08051391052008Proc. Natl. Acad. Sci. U.S.A.10510762-10767IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Cervix carcinomaIdentification and characterization of a novel human PP1 phosphatase complex.Lee J.H.You J.Dobrota E.Skalnik D.G.doi:10.1074/jbc.m110.1098012010J. Biol. Chem.28524466-24476INTERACTION WITH PPP1CA; PPP1CB AND PPP1CCQuantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.Olsen J.V.Vermeulen M.Santamaria A.Kumar C.Miller M.L.Jensen L.J.Gnad F.Cox J.Jensen T.S.Nigg E.A.Brunak S.Mann M.doi:10.1126/scisignal.20004752010Sci. Signal.3RA3IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Initial characterization of the human central proteome.Burkard T.R.Planyavsky M.Kaupe I.Breitwieser F.P.Buerckstuemmer T.Bennett K.L.Superti-Furga G.Colinge J.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.Rigbolt K.T.Prokhorova T.A.Akimov V.Henningsen J.Johansen P.T.Kratchmarova I.Kassem M.Mann M.Olsen J.V.Blagoev B.doi:10.1126/scisignal.20015702011Sci. Signal.4RS3IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Toward a comprehensive characterization of a human cancer cell phosphoproteome.Zhou H.Di Palma S.Preisinger C.Peng M.Polat A.N.Heck A.J.Mohammed S.doi:10.1021/pr300630k2013J. Proteome Res.12260-271PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]ErythroleukemiaAtlas of Genetics and Cytogenetics in Oncology and Haematology2.10B/D/F/H=158-216107271 site, 1 glycan1 site, 1 O-linked glycan (1 site)484 antibodies from 38 providershumanPPP1R8Low tissue specificitygeneEukaryotamRNA Splicing - Major Pathway746 hits in 1194 CRISPR screenshumanTbioProteinExpressed in calcaneal tendon and 216 other cell types or tissuesbaseline and differentialFHA_PPP1R8FHA_domSMAD_FHA_dom_sfKANADAPTIN-RELATEDNUCLEAR INHIBITOR OF PROTEIN PHOSPHATASE-1FHAFHASMAD/FHA domainFHA_DOMAINHSNuclear inhibitor of protein phosphatase 1NIPP-1Protein phosphatase 1 regulatory inhibitor subunit 8Activator of RNA decay3.1.4.-ARD-1PPP1R8ARD1NIPP1Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation.Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines and pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.Endoribonuclease function is magnesium-dependent.Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts with EED, in a nucleic acid-stimulated manner. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1. Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC.Primarily, but not exclusively, nuclear.Found mainly in the cytoplasm.Ubiquitously expressed, with highest levels in heart and skeletal muscle, followed by brain, placenta, lung, liver and pancreas. Less abundant in kidney. The concentration and ratio between isoforms is cell-type dependent. Isoform Alpha (>90%) and isoform Beta were found in brain, heart and kidney. Isoform Gamma is mainly found in B-cells and T-lymphocytes, and has been found in 293 embryonic kidney cells.Has a basic N- and C-terminal and an acidic central domain.The FHA domain mediates interactions with threonine-phosphorylated MELK.May be inactivated by phosphorylation on Ser-199 or Ser-204 (By similarity). Phosphorylated by Lyn in vitro on Tyr-264, and also on Tyr-335 in the presence of RNA.A synthetic peptide, NIPP-1(330-351), is able to inhibit PP-1. Phosphorylation of Tyr-335 reduces PP-1 inhibition, whereas phosphorylation of Thr-346 or Ser-348 has no effect.Nuclear inhibitor of protein phosphatase 1384791351FHA49101Interaction with CDC5L, SF3B1 and MELK142Interaction with EED143224Involved in PP-1 inhibition191200Involved in PP-1 binding203Interaction with EED310329Disordered316RNA-binding330Involved in PP-1 inhibition331337Nuclear localization signal 1185209Nuclear localization signal 2210240Phosphothreonine161Phosphoserine178Phosphoserine199Phosphoserine204Phosphoserine249Phosphotyrosine; by LYN; in vitro264Phosphotyrosine335In isoform Gamma.In isoform Beta.Abolishes interaction with CDC5L, SF3B1 and MELK, and localization in nuclear speckles. No effect on repressor activity.AAAA6871No effect on interaction with EED.AAAAA193197Abolishes nuclear import; when associated with A-234--237-A.AAA195No change in subcellular location, no effect on interaction with EED or repressor activity; when associated with A-204 or D-204.ADReduces PP-1 binding, no effect on subcellular location or repressor activity and prevents retargeting of PPP1CA and PPP1CC to nuclear speckles; when associated with A-203.A201Reduces PP-1 binding, no effect on subcellular location or repressor activity and prevents retargeting of PPP1CA and PPP1CC to nuclear speckles; when associated with A-201.ANo change in subcellular location, no effect on interaction with EED or repressor activity; when associated with A-199 or D-199.ADAbolishes nuclear import; when associated with A-195-197-A.AAAA234237Abolishes in vitro phosphorylation of isoform gamma by Lyn.DDecreases the ability of isoform Gamma to bind and inhibit PP-1.DNo effect on the ability of isoform Gamma to inhibit PP-1.D346No effect on the ability of isoform Gamma to inhibit PP-1.D348162174208false3false3false7false6false3false7false3false3APPBP2LRRK2PPP1CAPPP1CCRTN4IP12000-12-01238479f53f4f38a7cb4fc494c21d4c59a35528AlphaMAAAANSGSSLPLFDCPTWAGKPPPGLHLDVVKGDKLIEKLIIDEKKYYLFGRNPDLCDFTIDHQSCSRVHAALVYHKHLKRVFLIDLNSTHGTFLGHIRLEPHKPQQIPIDSTVSFGASTRAYTLREKPQTLPSAVKGDEKMGGEDDELKGLLGLPEEETELDNLTEFNTAHNKRISTLTIEEGNLDIQRPKRKRKNSRVTFSEDDEIINPEDVDPSVGRFRNMVQTAVVPVKKKRVEGPGSLGLEESGSRRMQNFAFSGGLYGGLPPTHSEAGSQPHGIHGTALIGGLPMPYPNLAPDVDLTPVVPSAVNMNPAPNPAVYNPEAVNEPKKKKYAKEAWPGKKPTPSLLIBetaDeltaMGGEDDELKGLLGLPEEETELDNLTEFNTAHNKRISTLTIEEGNLDIQRPKRKRKNSRVTFSEDDEIINPEDVDPSVGRFRNMVQTAVVPVKKKRVEGPGSLGLEESGSRRMQNFAFSGGLYGGLPPTHSEAGSQPHGIHGTALIGGLPMPYPNLAPDVDLTPVVPSAVNMNPAPNPAVYNPEAVNEPKKKKYAKEAWPGKKPTPSLLIGammaARD-1MVQTAVVPVKKKRVEGPGSLGLEESGSRRMQNFAFSGGLYGGLPPTHSEAGSQPHGIHGTALIGGLPMPYPNLAPDVDLTPVVPSAVNMNPAPNPAVYNPEAVNEPKKKKYAKEAWPGKKPTPSLLItruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue