PP1R8_HUMAN
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 03-AUG-2022, entry version 204.
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="http://atlasgeneticsoncology.org/Genes/PPP1R8ID41811ch1p35.html";
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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. [Q12972-3]
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; 81.
DR DIP; DIP-40815N; -.
DR ELM; Q12972; -.
DR IntAct; Q12972; 26.
DR MINT; Q12972; -.
DR STRING; 9606.ENSP00000311677; -.
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; Q12972; -.
DR PeptideAtlas; Q12972; -.
DR PRIDE; Q12972; -.
DR ProteomicsDB; 59067; -. [Q12972-1]
DR ProteomicsDB; 59068; -. [Q12972-2]
DR ProteomicsDB; 59069; -. [Q12972-3]
DR Antibodypedia; 16435; 424 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 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; HKHLNIA; -.
DR OrthoDB; 955935at2759; -.
DR PhylomeDB; Q12972; -.
DR TreeFam; TF105539; -.
DR PathwayCommons; Q12972; -.
DR SignaLink; Q12972; -.
DR SIGNOR; Q12972; -.
DR BioGRID-ORCS; 5511; 714 hits in 1106 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 214 other tissues.
DR ExpressionAtlas; Q12972; baseline and differential.
DR Genevisible; Q12972; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
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: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; cd00060; FHA; 1.
DR DisProt; DP00937; -.
DR IDEAL; IID00666; -.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF00498; FHA; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
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
