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 31-MAY-2011, entry version 77. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; 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 RT project: 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA 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 RP AND 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., RA Himpens B., 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). CC -!- FUNCTION: Inhibitor subunit of the major nuclear protein CC phosphatase-1 (PP-1). It has RNA-binding activity but does not CC cleave RNA and may target PP-1 to RNA-associated substrates. May CC also be involved in pre-mRNA splicing. Binds DNA and might act as CC a transcriptional repressor. Essential for cell proliferation and CC early embryonic development. CC -!- SUBUNIT: Interacts with phosphorylated CDC5L, SF3B1 and MELK. Part CC of 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. CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Nucleus speckle (By CC similarity). Note=Mainly, but not exclusively, nuclear. CC -!- DOMAIN: Has a basic N- and C-terminal and an acidic central CC domain. CC -!- PTM: May be inactivated by phosphorylation on Ser-199 or Ser-204 CC (By similarity). CC -!- DISRUPTION PHENOTYPE: Mice display a retarded growth and embryonic CC lethality at E6.5, due to defects in proliferation rate. CC -!- SIMILARITY: Contains 1 FHA domain. 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 IPI; IPI00153750; -. DR RefSeq; NP_666266.1; NM_146154.2. DR UniGene; Mm.105230; -. DR PDB; 2JPE; NMR; -; A=1-132. DR PDBsum; 2JPE; -. DR ProteinModelPortal; Q8R3G1; -. DR SMR; Q8R3G1; 1-132. DR STRING; Q8R3G1; -. DR PhosphoSite; Q8R3G1; -. DR PRIDE; Q8R3G1; -. DR Ensembl; ENSMUST00000030702; ENSMUSP00000030702; ENSMUSG00000028882. DR GeneID; 100336; -. DR KEGG; mmu:100336; -. DR UCSC; uc008vbw.1; mouse. DR CTD; 100336; -. DR MGI; MGI:2140494; Ppp1r8. DR GeneTree; ENSGT00510000047324; -. DR HOGENOM; HBG377810; -. DR HOVERGEN; HBG053645; -. DR InParanoid; Q8R3G1; -. DR OMA; VKKKRME; -. DR OrthoDB; EOG45HRXT; -. DR PhylomeDB; Q8R3G1; -. DR NextBio; 354398; -. DR ArrayExpress; Q8R3G1; -. DR Bgee; Q8R3G1; -. DR Genevestigator; Q8R3G1; -. DR GermOnline; ENSMUSG00000028882; Mus musculus. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0008599; F:protein phosphatase type 1 regulator activity; IDA:MGI. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0008283; P:cell proliferation; IMP:MGI. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR InterPro; IPR000253; FHA_dom. DR InterPro; IPR008984; SMAD_FHA_domain. DR Gene3D; G3DSA:2.60.200.20; FHA; 1. DR Pfam; PF00498; FHA; 1. DR SMART; SM00240; FHA; 1. DR SUPFAM; SSF49879; SMAD_FHA; 1. DR PROSITE; PS50006; FHA_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Developmental protein; DNA-binding; KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; KW Protein phosphatase inhibitor; Repressor; RNA-binding; Spliceosome; KW Transcription; Transcription regulation. FT CHAIN 1 351 Nuclear inhibitor of protein phosphatase FT 1. FT /FTId=PRO_0000071506. FT DOMAIN 49 101 FHA. FT REGION 1 142 Interaction with CDC5L, SF3B1 and MELK FT (By similarity). FT REGION 143 224 Interaction with EED (By similarity). FT REGION 191 200 Involved in PP-1 inhibition (By FT similarity). FT REGION 200 203 Involved in PP-1 binding (By similarity). FT REGION 310 329 Interaction with EED (By similarity). FT REGION 330 351 RNA-binding (By similarity). FT REGION 331 337 Involved in PP-1 inhibition (By FT similarity). FT MOTIF 185 209 Nuclear localization signal 1 (By FT similarity). FT MOTIF 210 240 Nuclear localization signal 2 (By FT similarity). FT COMPBIAS 2 5 Poly-Ala. FT COMPBIAS 331 334 Poly-Lys. FT MOD_RES 199 199 Phosphoserine (By similarity). FT MOD_RES 204 204 Phosphoserine (By similarity). FT MOD_RES 335 335 Phosphotyrosine (By similarity). FT STRAND 7 9 FT STRAND 18 20 FT STRAND 28 41 FT STRAND 51 53 FT TURN 55 57 FT STRAND 58 60 FT STRAND 65 67 FT STRAND 71 80 FT STRAND 83 86 FT STRAND 94 98 FT STRAND 103 105 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 //