PP1R8_MOUSE
ID PP1R8_MOUSE Reviewed; 351 AA.
AC Q8R3G1; Q8C087;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Nuclear inhibitor of protein phosphatase 1;
DE Short=NIPP-1;
DE AltName: Full=Protein phosphatase 1 regulatory inhibitor subunit 8;
GN Name=Ppp1r8; Synonyms=Nipp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 46-351.
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP INTERACTION WITH EED, AND IDENTIFICATION IN A COMPLEX WITH EED; HDAC2 AND
RP PP1.
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 [4]
RP FUNCTION.
RX PubMed=15501817; DOI=10.1074/jbc.m411911200;
RA Lesage B., Beullens M., Nuytten M., Van Eynde A., Keppens S., Himpens B.,
RA Bollen M.;
RT "Interactor-mediated nuclear translocation and retention of protein
RT phosphatase-1.";
RL J. Biol. Chem. 279:55978-55984(2004).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15199142; DOI=10.1128/mcb.24.13.5863-5874.2004;
RA Van Eynde A., Nuytten M., Dewerchin M., Schoonjans L., Keppens S.,
RA Beullens M., Moons L., Carmeliet P., Stalmans W., Bollen M.;
RT "The nuclear scaffold protein NIPP1 is essential for early embryonic
RT development and cell proliferation.";
RL Mol. Cell. Biol. 24:5863-5874(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP STRUCTURE BY NMR OF 1-132, DOMAIN FHA, AND INTERACTION WITH MELK.
RX PubMed=18253837; DOI=10.1007/s10858-008-9222-x;
RA Kumeta H., Ogura K., Adachi S., Fujioka Y., Tanuma N., Kikuchi K.,
RA Inagaki F.;
RT "The NMR structure of the NIPP1 FHA domain.";
RL J. Biomol. NMR 40:219-224(2008).
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 Essential for cell proliferation and early embryonic development.
CC {ECO:0000269|PubMed:15199142, ECO:0000269|PubMed:15501817}.
CC -!- SUBUNIT: Interacts with phosphorylated CDC5L, SF3B1 and MELK. Part of
CC the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC (By
CC similarity). Interacts with EED. Part of a complex consisting of
CC PPP1R8, EED, HDAC2 and PP-1. {ECO:0000250, ECO:0000269|PubMed:12788942,
CC ECO:0000269|PubMed:18253837}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus speckle
CC {ECO:0000250}. Note=Mainly, but not exclusively, nuclear.
CC -!- DOMAIN: Has a basic N- and C-terminal and an acidic central domain.
CC {ECO:0000269|PubMed:18253837}.
CC -!- DOMAIN: The FHA domain mediates interactions with threonine-
CC phosphorylated MELK. {ECO:0000269|PubMed:18253837}.
CC -!- PTM: May be inactivated by phosphorylation on Ser-199 or Ser-204.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice display a retarded growth and embryonic
CC lethality at E6.5, due to defects in proliferation rate.
CC {ECO:0000269|PubMed:15199142}.
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DR EMBL; BC025479; AAH25479.1; -; mRNA.
DR EMBL; AK032022; BAC27653.1; -; mRNA.
DR CCDS; CCDS18736.1; -.
DR RefSeq; NP_001277654.1; NM_001290725.1.
DR RefSeq; NP_666266.1; NM_146154.3.
DR PDB; 2JPE; NMR; -; A=1-132.
DR PDBsum; 2JPE; -.
DR AlphaFoldDB; Q8R3G1; -.
DR BMRB; Q8R3G1; -.
DR SMR; Q8R3G1; -.
DR BioGRID; 221435; 8.
DR IntAct; Q8R3G1; 1.
DR STRING; 10090.ENSMUSP00000030702; -.
DR iPTMnet; Q8R3G1; -.
DR PhosphoSitePlus; Q8R3G1; -.
DR EPD; Q8R3G1; -.
DR jPOST; Q8R3G1; -.
DR MaxQB; Q8R3G1; -.
DR PaxDb; Q8R3G1; -.
DR PRIDE; Q8R3G1; -.
DR ProteomicsDB; 291774; -.
DR Antibodypedia; 16435; 424 antibodies from 38 providers.
DR DNASU; 100336; -.
DR Ensembl; ENSMUST00000030702; ENSMUSP00000030702; ENSMUSG00000028882.
DR GeneID; 100336; -.
DR KEGG; mmu:100336; -.
DR UCSC; uc008vbw.3; mouse.
DR CTD; 5511; -.
DR MGI; MGI:2140494; Ppp1r8.
DR VEuPathDB; HostDB:ENSMUSG00000028882; -.
DR eggNOG; KOG1880; Eukaryota.
DR GeneTree; ENSGT00940000156115; -.
DR HOGENOM; CLU_069628_0_0_1; -.
DR InParanoid; Q8R3G1; -.
DR OMA; HKHLNIA; -.
DR OrthoDB; 955935at2759; -.
DR PhylomeDB; Q8R3G1; -.
DR TreeFam; TF105539; -.
DR BioGRID-ORCS; 100336; 31 hits in 78 CRISPR screens.
DR ChiTaRS; Ppp1r8; mouse.
DR EvolutionaryTrace; Q8R3G1; -.
DR PRO; PR:Q8R3G1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8R3G1; protein.
DR Bgee; ENSMUSG00000028882; Expressed in optic fissure and 250 other tissues.
DR ExpressionAtlas; Q8R3G1; baseline and differential.
DR Genevisible; Q8R3G1; MM.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0019888; F:protein phosphatase regulator activity; IDA:MGI.
DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
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:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd00060; FHA; 1.
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; Developmental protein; DNA-binding; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Protein phosphatase inhibitor;
KW Reference proteome; Repressor; RNA-binding; Spliceosome; Transcription;
KW Transcription regulation.
FT CHAIN 1..351
FT /note="Nuclear inhibitor of protein phosphatase 1"
FT /id="PRO_0000071506"
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:0000250"
FT REGION 143..224
FT /note="Interaction with EED"
FT /evidence="ECO:0000250"
FT REGION 191..200
FT /note="Involved in PP-1 inhibition"
FT /evidence="ECO:0000250"
FT REGION 200..203
FT /note="Involved in PP-1 binding"
FT /evidence="ECO:0000250"
FT REGION 310..329
FT /note="Interaction with EED"
FT /evidence="ECO:0000250"
FT REGION 314..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..351
FT /note="RNA-binding"
FT /evidence="ECO:0000250"
FT REGION 331..337
FT /note="Involved in PP-1 inhibition"
FT /evidence="ECO:0000250"
FT MOTIF 185..209
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 210..240
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:Q12972"
FT MOD_RES 264
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q12972"
FT MOD_RES 335
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q12972"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 28..41
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2JPE"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 71..80
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:2JPE"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2JPE"
SQ SEQUENCE 351 AA; 38528 MW; D3A3BC4B2DF467A2 CRC64;
MAAAVNSGSS LPLFDCPTWA GKPPPGLHLD VVKGDKLIEK LIIDEKKYYL FGRNPDLCDF
TIDHQSCSRV HAALVYHKHL KRVFLIDLNS THGTFLGHIR LEPHKPQQIP IDSTVSFGAS
TRAYTLREKP QTLPSAVKGD EKMGGEDDEL KGLLGLPEEE TELDNLTEFN TAHNKRISTL
TIEEGNLDIQ RPKRKRKNSR VTFSEDDEII NPEDVDPSVG RFRNMVQTAV VPVKKKRMEG
SGSLGLEESG SRRMQNFAFS GGLYGGLPPT HSETGSQPHG IHGTALIGGL PMPYPNLAPD
VDLTPVVPSA VAINPTPNPA VYNPEAVNEP KKKKYAKEAW PGKKPTPSLL I
