ID PP1R8_HUMAN Reviewed; 351 AA. AC Q12972; Q5TEJ2; Q5TEJ4; Q5TIF2; Q6PKF6; Q9UBH1; Q9UBZ0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=Nuclear inhibitor of protein phosphatase 1; DE Short=NIPP-1; DE AltName: Full=Protein phosphatase 1 regulatory inhibitor subunit 8; DE Includes: DE RecName: Full=Activator of RNA decay; DE EC=3.1.4.-; DE AltName: Full=ARD-1; GN Name=PPP1R8; Synonyms=ARD1, NIPP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA). RC TISSUE=B-cell; RX PubMed=7524097; DOI=10.1073/pnas.91.22.10591; RA Wang M., Cohen S.N.; RT "ard-1: a human gene that reverses the effects of temperature-sensitive and RT deletion mutations in the Escherichia coli rne gene and encodes an activity RT producing RNase E-like cleavages."; RL Proc. Natl. Acad. Sci. U.S.A. 91:10591-10595(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA AND BETA), RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RC TISSUE=Parathyroid, and T-cell; RX PubMed=10103062; DOI=10.1046/j.1432-1327.1999.00272.x; RA Van Eynde A., Perez-Callejon E., Schoenmakers E., Jacquemin M., RA Stalmans W., Bollen M.; RT "Organization and alternate splice products of the gene encoding nuclear RT inhibitor of protein phosphatase-1 (NIPP-1)."; RL Eur. J. Biochem. 261:291-300(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). RC TISSUE=Mammary cancer; RA Liu J.P., Yang Z., Li H.; RT "Complete cDNA sequence of NIPP-1 from human breast cancer cells."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 34-351 (ISOFORM ALPHA). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP TISSUE SPECIFICITY. RX PubMed=7499293; DOI=10.1074/jbc.270.47.28068; RA Van Eynde A., Wera S., Beullens M., Torrekens S., Van Leuven F., RA Stalmans W., Bollen M.; RT "Molecular cloning of NIPP-1, a nuclear inhibitor of protein phosphatase-1, RT reveals homology with polypeptides involved in RNA processing."; RL J. Biol. Chem. 270:28068-28074(1995). RN [9] RP CHARACTERIZATION (ISOFORM GAMMA). RX PubMed=9153239; DOI=10.1074/jbc.272.21.13823; RA Claverie-Martin F., Wang M., Cohen S.N.; RT "ARD-1 cDNA from human cells encodes a site-specific single-strand RT endoribonuclease that functionally resembles Escherichia coli RNase E."; RL J. Biol. Chem. 272:13823-13828(1997). RN [10] RP RNA-BINDING, CHARACTERIZATION (ISOFORM GAMMA), AND FUNCTION. RX PubMed=10432294; DOI=10.1042/bj3420013; RA Jin Q., Beullens M., Jagiello I., Van Eynde A., Vulsteke V., Stalmans W., RA Bollen M.; RT "Mapping of the RNA-binding and endoribonuclease domains of NIPP1, a RT nuclear targeting subunit of protein phosphatase 1."; RL Biochem. J. 342:13-19(1999). RN [11] RP IDENTIFICATION OF ALTERNATIVE SPLICING IN ISOFORM GAMMA. RX PubMed=10564811; DOI=10.1016/s0378-1119(99)00435-7; RA Chang A.C.Y., Sohlberg B., Trinkle-Mulcahy L., Claverie-Martin F., RA Cohen P., Cohen S.N.; RT "Alternative splicing regulates the production of ARD-1 endoribonuclease RT and NIPP-1, an inhibitor of protein phosphatase-1, as isoforms encoded by RT the same gene."; RL Gene 240:45-55(1999). RN [12] RP FUNCTION, MUTAGENESIS OF TYR-264; TYR-335; THR-346 AND SER-348, AND RP PHOSPHORYLATION AT TYR-264 AND TYR-335. RX PubMed=11104670; DOI=10.1042/bj3520651; RA Beullens M., Vulsteke V., Van Eynde A., Jagiello I., Stalmans W., RA Bollen M.; RT "The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) RT contains a novel binding site for protein phosphatase-1 that is controlled RT by tyrosine phosphorylation and RNA binding."; RL Biochem. J. 352:651-658(2000). RN [13] RP INTERACTION WITH CDC5L, SUBCELLULAR LOCATION, MUTAGENESIS OF RP 68-SER--HIS-71, AND FUNCTION. RX PubMed=10827081; DOI=10.1074/jbc.m001676200; RA Boudrez A., Beullens M., Groenen P.M.A., Van Eynde A., Vulsteke V., RA Jagiello I., Murray M., Krainer A.R., Stalmans W., Bollen M.; RT "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a RT regulator of pre-mRNA splicing and mitotic entry."; RL J. Biol. Chem. 275:25411-25417(2000). RN [14] RP NUCLEAR LOCALIZATION SIGNALS, MUTAGENESIS OF 68-SER--HIS-71; RP 195-LYS--LYS-197; SER-199; VAL-201; PHE-203; SER-204 AND 234-LYS--ARG-237, RP AND SUBCELLULAR LOCATION. RX PubMed=11034904; DOI=10.1242/jcs.113.21.3761; RA Jagiello I., Van Eynde A., Vulsteke V., Beullens M., Boudrez A., RA Keppens S., Stalmans W., Bollen M.; RT "Nuclear and subnuclear targeting sequences of the protein phosphatase-1 RT regulator NIPP1."; RL J. Cell Sci. 113:3761-3768(2000). RN [15] RP SUBCELLULAR LOCATION, INTERACTION WITH PPP1CA AND PPP1CC, AND MUTAGENESIS RP OF VAL-201 AND PHE-203. RX PubMed=11739654; DOI=10.1242/jcs.114.23.4219; RA Trinkle-Mulcahy L., Sleeman J.E., Lamond A.I.; RT "Dynamic targeting of protein phosphatase 1 within the nuclei of living RT mammalian cells."; RL J. Cell Sci. 114:4219-4228(2001). RN [16] RP IDENTIFICATION AS PART OF THE SPLICEOSOME, AND FUNCTION. RX PubMed=11909864; DOI=10.1074/jbc.m200847200; RA Beullens M., Bollen M.; RT "The protein phosphatase-1 regulator NIPP1 is also a splicing factor RT involved in a late step of spliceosome assembly."; RL J. Biol. Chem. 277:19855-19860(2002). RN [17] RP INTERACTION WITH SF3B1, AND MUTAGENESIS OF 68-SER--HIS-71. RX PubMed=12105215; DOI=10.1074/jbc.m204427200; RA Boudrez A., Beullens M., Waelkens E., Stalmans W., Bollen M.; RT "Phosphorylation-dependent interaction between the splicing factors SAP155 RT and NIPP1."; RL J. Biol. Chem. 277:31834-31841(2002). RN [18] RP DNA-BINDING, INTERACTION WITH EED, IDENTIFICATION IN A COMPLEX WITH EED; RP HDAC2 AND PP1, MUTAGENESIS OF 68-SER--HIS-71; 193-LYS--LYS-197; SER-199; RP VAL-201; PHE-203 AND SER-204, AND FUNCTION. RX PubMed=12788942; DOI=10.1074/jbc.m302273200; RA Jin Q., van Eynde A., Beullens M., Roy N., Thiel G., Stalmans W., RA Bollen M.; RT "The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 RT (NIPP1), interacts with the polycomb group protein, embryonic ectoderm RT development (EED), and functions as a transcriptional repressor."; RL J. Biol. Chem. 278:30677-30685(2003). RN [19] RP INTERACTION WITH MELK, AND MUTAGENESIS OF 68-SER--HIS-71. RX PubMed=14699119; DOI=10.1074/jbc.m311466200; RA Vulsteke V., Beullens M., Boudrez A., Keppens S., Van Eynde A., Rider M.H., RA Stalmans W., Bollen M.; RT "Inhibition of spliceosome assembly by the cell cycle-regulated protein RT kinase MELK and involvement of splicing factor NIPP1."; RL J. Biol. Chem. 279:8642-8647(2004). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [21] RP INTERACTION WITH PPP1CA; PPP1CB AND PPP1CC. RX PubMed=20516061; DOI=10.1074/jbc.m110.109801; RA Lee J.H., You J., Dobrota E., Skalnik D.G.; RT "Identification and characterization of a novel human PP1 phosphatase RT complex."; RL J. Biol. Chem. 285:24466-24476(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). CC -!- FUNCTION: Inhibitor subunit of the major nuclear protein phosphatase-1 CC (PP-1). It has RNA-binding activity but does not cleave RNA and may CC target PP-1 to RNA-associated substrates. May also be involved in pre- CC mRNA splicing. Binds DNA and might act as a transcriptional repressor. CC Seems to be required for cell proliferation. CC -!- FUNCTION: Isoform Gamma is a site-specific single-strand CC endoribonuclease that cleaves single strand RNA 3' to purines and CC pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at CC the site of cleavage. This isoform does not inhibit PP-1. May be CC implicated in mRNA splicing. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Endoribonuclease function is magnesium-dependent.; CC -!- SUBUNIT: Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts CC with EED, in a nucleic acid-stimulated manner. Part of a complex CC consisting of PPP1R8, EED, HDAC2 and PP-1. Part of the spliceosome. CC Interacts with PPP1CA, PPP1CB and PPP1CC. {ECO:0000269|PubMed:10827081, CC ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:12105215, CC ECO:0000269|PubMed:12788942, ECO:0000269|PubMed:14699119, CC ECO:0000269|PubMed:20516061}. CC -!- INTERACTION: CC Q12972; Q92624: APPBP2; NbExp=3; IntAct=EBI-716633, EBI-743771; CC Q12972; Q5S007: LRRK2; NbExp=3; IntAct=EBI-716633, EBI-5323863; CC Q12972; P62136: PPP1CA; NbExp=7; IntAct=EBI-716633, EBI-357253; CC Q12972-1; P62136: PPP1CA; NbExp=6; IntAct=EBI-16012257, EBI-357253; CC Q12972-2; Q92624: APPBP2; NbExp=3; IntAct=EBI-12252736, EBI-743771; CC Q12972-2; P62136: PPP1CA; NbExp=7; IntAct=EBI-12252736, EBI-357253; CC Q12972-2; P36873: PPP1CC; NbExp=3; IntAct=EBI-12252736, EBI-356283; CC Q12972-2; Q8WWV3: RTN4IP1; NbExp=3; IntAct=EBI-12252736, EBI-743502; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Primarily, but not CC exclusively, nuclear. CC -!- SUBCELLULAR LOCATION: [Isoform Gamma]: Cytoplasm. Note=Found mainly in CC the cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Alpha; CC IsoId=Q12972-1; Sequence=Displayed; CC Name=Beta; Synonyms=Delta; CC IsoId=Q12972-2; Sequence=VSP_005119; CC Name=Gamma; Synonyms=ARD-1; CC IsoId=Q12972-3; Sequence=VSP_005120; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in CC heart and skeletal muscle, followed by brain, placenta, lung, liver and CC pancreas. Less abundant in kidney. The concentration and ratio between CC isoforms is cell-type dependent. Isoform Alpha (>90%) and isoform Beta CC were found in brain, heart and kidney. Isoform Gamma is mainly found in CC B-cells and T-lymphocytes, and has been found in 293 embryonic kidney CC cells. {ECO:0000269|PubMed:10103062, ECO:0000269|PubMed:7499293}. CC -!- DOMAIN: Has a basic N- and C-terminal and an acidic central domain. CC -!- DOMAIN: The FHA domain mediates interactions with threonine- CC phosphorylated MELK. {ECO:0000250}. CC -!- PTM: May be inactivated by phosphorylation on Ser-199 or Ser-204 (By CC similarity). Phosphorylated by Lyn in vitro on Tyr-264, and also on CC Tyr-335 in the presence of RNA. {ECO:0000250, CC ECO:0000269|PubMed:11104670}. CC -!- MISCELLANEOUS: A synthetic peptide, NIPP-1(330-351), is able to inhibit CC PP-1. Phosphorylation of Tyr-335 reduces PP-1 inhibition, whereas CC phosphorylation of Thr-346 or Ser-348 has no effect. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41811/PPP1R8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U14575; AAA64749.1; -; mRNA. DR EMBL; AF061958; AAD31541.1; -; mRNA. DR EMBL; AF061959; AAD31542.1; -; mRNA. DR EMBL; AF064757; AAD24669.1; -; Genomic_DNA. DR EMBL; AF064751; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064752; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064753; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064754; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064755; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064756; AAD24669.1; JOINED; Genomic_DNA. DR EMBL; AF064757; AAD24670.1; -; Genomic_DNA. DR EMBL; AF064754; AAD24670.1; JOINED; Genomic_DNA. DR EMBL; AF064755; AAD24670.1; JOINED; Genomic_DNA. DR EMBL; AF064756; AAD24670.1; JOINED; Genomic_DNA. DR EMBL; AF126488; AAD22486.1; -; mRNA. DR EMBL; AK292077; BAF84766.1; -; mRNA. DR EMBL; AL020997; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL109927; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07731.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07732.1; -; Genomic_DNA. DR EMBL; BC001597; AAH01597.1; -; mRNA. DR EMBL; BC013360; AAH13360.1; -; mRNA. DR CCDS; CCDS311.1; -. [Q12972-1] DR CCDS; CCDS312.1; -. [Q12972-2] DR CCDS; CCDS313.1; -. [Q12972-3] DR PIR; I38856; I38856. DR RefSeq; NP_002704.1; NM_002713.3. [Q12972-3] DR RefSeq; NP_054829.2; NM_014110.4. [Q12972-1] DR RefSeq; NP_612568.1; NM_138558.2. [Q12972-2] DR RefSeq; XP_016857083.1; XM_017001594.1. DR PDB; 3V4Y; X-ray; 2.10 A; B/D/F/H=158-216. DR PDBsum; 3V4Y; -. DR AlphaFoldDB; Q12972; -. DR BMRB; Q12972; -. DR SMR; Q12972; -. DR BioGRID; 111503; 107. DR DIP; DIP-40815N; -. DR ELM; Q12972; -. DR IntAct; Q12972; 27. DR MINT; Q12972; -. DR STRING; 9606.ENSP00000311677; -. DR GlyCosmos; Q12972; 1 site, 1 glycan. DR GlyGen; Q12972; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q12972; -. DR MetOSite; Q12972; -. DR PhosphoSitePlus; Q12972; -. DR BioMuta; PPP1R8; -. DR DMDM; 19863082; -. DR EPD; Q12972; -. DR jPOST; Q12972; -. DR MassIVE; Q12972; -. DR MaxQB; Q12972; -. DR PaxDb; 9606-ENSP00000311677; -. DR PeptideAtlas; Q12972; -. DR ProteomicsDB; 59067; -. [Q12972-1] DR ProteomicsDB; 59068; -. [Q12972-2] DR ProteomicsDB; 59069; -. [Q12972-3] DR Pumba; Q12972; -. DR Antibodypedia; 16435; 484 antibodies from 38 providers. DR DNASU; 5511; -. DR Ensembl; ENST00000236412.11; ENSP00000236412.7; ENSG00000117751.18. [Q12972-3] DR Ensembl; ENST00000311772.10; ENSP00000311677.5; ENSG00000117751.18. [Q12972-1] DR Ensembl; ENST00000373931.8; ENSP00000363042.4; ENSG00000117751.18. [Q12972-2] DR GeneID; 5511; -. DR KEGG; hsa:5511; -. DR MANE-Select; ENST00000311772.10; ENSP00000311677.5; NM_014110.5; NP_054829.2. DR UCSC; uc001bov.3; human. [Q12972-1] DR AGR; HGNC:9296; -. DR CTD; 5511; -. DR DisGeNET; 5511; -. DR GeneCards; PPP1R8; -. DR HGNC; HGNC:9296; PPP1R8. DR HPA; ENSG00000117751; Low tissue specificity. DR MIM; 602636; gene. DR neXtProt; NX_Q12972; -. DR OpenTargets; ENSG00000117751; -. DR PharmGKB; PA33659; -. DR VEuPathDB; HostDB:ENSG00000117751; -. DR eggNOG; KOG1880; Eukaryota. DR GeneTree; ENSGT00940000156115; -. DR HOGENOM; CLU_069628_0_0_1; -. DR InParanoid; Q12972; -. DR OMA; NSTFHFG; -. DR OrthoDB; 4248727at2759; -. DR PhylomeDB; Q12972; -. DR TreeFam; TF105539; -. DR PathwayCommons; Q12972; -. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR SignaLink; Q12972; -. DR SIGNOR; Q12972; -. DR BioGRID-ORCS; 5511; 746 hits in 1194 CRISPR screens. DR ChiTaRS; PPP1R8; human. DR GeneWiki; PPP1R8; -. DR GenomeRNAi; 5511; -. DR Pharos; Q12972; Tbio. DR PRO; PR:Q12972; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q12972; Protein. DR Bgee; ENSG00000117751; Expressed in calcaneal tendon and 216 other cell types or tissues. DR ExpressionAtlas; Q12972; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0140678; F:molecular function inhibitor activity; EXP:DisProt. DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central. DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; IBA:GO_Central. DR GO; GO:0008995; F:ribonuclease E activity; TAS:ProtInc. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IBA:GO_Central. DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR CDD; cd22674; FHA_PPP1R8; 1. DR DisProt; DP00937; -. DR Gene3D; 2.60.200.20; -; 1. DR Gene3D; 6.10.250.1290; -; 1. DR IDEAL; IID00666; -. DR InterPro; IPR000253; FHA_dom. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR PANTHER; PTHR23308:SF53; KANADAPTIN-RELATED; 1. DR PANTHER; PTHR23308; NUCLEAR INHIBITOR OF PROTEIN PHOSPHATASE-1; 1. DR Pfam; PF00498; FHA; 1. DR SMART; SM00240; FHA; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR PROSITE; PS50006; FHA_DOMAIN; 1. DR Genevisible; Q12972; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; DNA-binding; Endonuclease; KW Hydrolase; Magnesium; mRNA processing; mRNA splicing; Nuclease; Nucleus; KW Phosphoprotein; Protein phosphatase inhibitor; Reference proteome; Repeat; KW Repressor; RNA-binding; Spliceosome; Transcription; KW Transcription regulation. FT CHAIN 1..351 FT /note="Nuclear inhibitor of protein phosphatase 1" FT /id="PRO_0000071505" FT DOMAIN 49..101 FT /note="FHA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086" FT REGION 1..142 FT /note="Interaction with CDC5L, SF3B1 and MELK" FT /evidence="ECO:0000269|PubMed:10827081, FT ECO:0000269|PubMed:12105215, ECO:0000269|PubMed:14699119" FT REGION 143..224 FT /note="Interaction with EED" FT /evidence="ECO:0000269|PubMed:12788942" FT REGION 191..200 FT /note="Involved in PP-1 inhibition" FT REGION 200..203 FT /note="Involved in PP-1 binding" FT REGION 310..329 FT /note="Interaction with EED" FT /evidence="ECO:0000269|PubMed:12788942" FT REGION 316..351 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 330..351 FT /note="RNA-binding" FT REGION 331..337 FT /note="Involved in PP-1 inhibition" FT MOTIF 185..209 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000269|PubMed:11034904" FT MOTIF 210..240 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000269|PubMed:11034904" FT MOD_RES 161 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q28147" FT MOD_RES 178 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28147" FT MOD_RES 199 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28147" FT MOD_RES 204 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28147" FT MOD_RES 249 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 264 FT /note="Phosphotyrosine; by LYN; in vitro" FT /evidence="ECO:0000269|PubMed:11104670" FT MOD_RES 335 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:11104670" FT VAR_SEQ 1..224 FT /note="Missing (in isoform Gamma)" FT /evidence="ECO:0000303|PubMed:7524097" FT /id="VSP_005120" FT VAR_SEQ 1..142 FT /note="Missing (in isoform Beta)" FT /evidence="ECO:0000303|PubMed:10103062, FT ECO:0000303|PubMed:15489334" FT /id="VSP_005119" FT MUTAGEN 68..71 FT /note="SRVH->AAAA: Abolishes interaction with CDC5L, SF3B1 FT and MELK, and localization in nuclear speckles. No effect FT on repressor activity." FT /evidence="ECO:0000269|PubMed:10827081, FT ECO:0000269|PubMed:11034904, ECO:0000269|PubMed:12105215, FT ECO:0000269|PubMed:12788942, ECO:0000269|PubMed:14699119" FT MUTAGEN 193..197 FT /note="KRKRK->AAAAA: No effect on interaction with EED." FT /evidence="ECO:0000269|PubMed:12788942" FT MUTAGEN 195..197 FT /note="KRK->AAA: Abolishes nuclear import; when associated FT with A-234--237-A." FT /evidence="ECO:0000269|PubMed:11034904" FT MUTAGEN 199 FT /note="S->A,D: No change in subcellular location, no effect FT on interaction with EED or repressor activity; when FT associated with A-204 or D-204." FT /evidence="ECO:0000269|PubMed:11034904, FT ECO:0000269|PubMed:12788942" FT MUTAGEN 201 FT /note="V->A: Reduces PP-1 binding, no effect on subcellular FT location or repressor activity and prevents retargeting of FT PPP1CA and PPP1CC to nuclear speckles; when associated with FT A-203." FT /evidence="ECO:0000269|PubMed:11034904, FT ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:12788942" FT MUTAGEN 203 FT /note="F->A: Reduces PP-1 binding, no effect on subcellular FT location or repressor activity and prevents retargeting of FT PPP1CA and PPP1CC to nuclear speckles; when associated with FT A-201." FT /evidence="ECO:0000269|PubMed:11034904, FT ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:12788942" FT MUTAGEN 204 FT /note="S->A,D: No change in subcellular location, no effect FT on interaction with EED or repressor activity; when FT associated with A-199 or D-199." FT /evidence="ECO:0000269|PubMed:11034904, FT ECO:0000269|PubMed:12788942" FT MUTAGEN 234..237 FT /note="KKKR->AAAA: Abolishes nuclear import; when FT associated with A-195-197-A." FT /evidence="ECO:0000269|PubMed:11034904" FT MUTAGEN 264 FT /note="Y->D: Abolishes in vitro phosphorylation of isoform FT gamma by Lyn." FT /evidence="ECO:0000269|PubMed:11104670" FT MUTAGEN 335 FT /note="Y->D: Decreases the ability of isoform Gamma to bind FT and inhibit PP-1." FT /evidence="ECO:0000269|PubMed:11104670" FT MUTAGEN 346 FT /note="T->D: No effect on the ability of isoform Gamma to FT inhibit PP-1." FT /evidence="ECO:0000269|PubMed:11104670" FT MUTAGEN 348 FT /note="S->D: No effect on the ability of isoform Gamma to FT inhibit PP-1." FT /evidence="ECO:0000269|PubMed:11104670" FT HELIX 162..174 FT /evidence="ECO:0007829|PDB:3V4Y" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:3V4Y" SQ SEQUENCE 351 AA; 38479 MW; 0A0E92B033E37641 CRC64; MAAAANSGSS LPLFDCPTWA GKPPPGLHLD VVKGDKLIEK LIIDEKKYYL FGRNPDLCDF TIDHQSCSRV HAALVYHKHL KRVFLIDLNS THGTFLGHIR LEPHKPQQIP IDSTVSFGAS TRAYTLREKP QTLPSAVKGD EKMGGEDDEL KGLLGLPEEE TELDNLTEFN TAHNKRISTL TIEEGNLDIQ RPKRKRKNSR VTFSEDDEII NPEDVDPSVG RFRNMVQTAV VPVKKKRVEG PGSLGLEESG SRRMQNFAFS GGLYGGLPPT HSEAGSQPHG IHGTALIGGL PMPYPNLAPD VDLTPVVPSA VNMNPAPNPA VYNPEAVNEP KKKKYAKEAW PGKKPTPSLL I //