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 26-FEB-2020, entry version 135. 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}. 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; 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 SMR; Q8R3G1; -. DR IntAct; Q8R3G1; 2. DR MINT; Q8R3G1; -. DR STRING; 10090.ENSMUSP00000030702; -. DR iPTMnet; Q8R3G1; -. DR PhosphoSitePlus; Q8R3G1; -. DR EPD; Q8R3G1; -. DR MaxQB; Q8R3G1; -. DR PaxDb; Q8R3G1; -. DR PRIDE; Q8R3G1; -. 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 eggNOG; KOG1880; Eukaryota. DR eggNOG; ENOG410XTHZ; LUCA. DR GeneTree; ENSGT00940000156115; -. DR HOGENOM; CLU_069628_0_0_1; -. DR InParanoid; Q8R3G1; -. DR KO; K13216; -. DR OMA; HKHLNIA; -. DR OrthoDB; 955935at2759; -. DR PhylomeDB; Q8R3G1; -. DR TreeFam; TF105539; -. 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 mandibular prominence and 277 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:0007275; P:multicellular organism development; 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 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 COMPBIAS 2..5 FT /note="Poly-Ala" FT COMPBIAS 331..334 FT /note="Poly-Lys" 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:0000244|PDB:2JPE" FT STRAND 18..20 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 28..41 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 51..53 FT /evidence="ECO:0000244|PDB:2JPE" FT TURN 55..57 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 58..60 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 65..67 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 71..80 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 83..86 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 94..98 FT /evidence="ECO:0000244|PDB:2JPE" FT STRAND 103..105 FT /evidence="ECO:0000244|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 //