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 05-DEC-2018, entry version 128. 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; Myomorpha; 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). 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 RT 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 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. {ECO:0000269|PubMed:15199142, CC ECO:0000269|PubMed:15501817}. 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. {ECO:0000250, CC ECO:0000269|PubMed:12788942, 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 CC domain. {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 UniGene; Mm.105230; -. DR PDB; 2JPE; NMR; -; A=1-132. DR PDBsum; 2JPE; -. DR ProteinModelPortal; Q8R3G1; -. 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; HOG000231315; -. DR HOVERGEN; HBG053645; -. DR InParanoid; Q8R3G1; -. DR KO; K13216; -. DR OMA; DEKRCYL; -. DR OrthoDB; EOG091G0D26; -. DR PhylomeDB; Q8R3G1; -. DR TreeFam; TF105539; -. DR ChiTaRS; Ppp1r8; mouse. DR EvolutionaryTrace; Q8R3G1; -. DR PRO; PR:Q8R3G1; -. DR Proteomes; UP000000589; Chromosome 4. DR Bgee; ENSMUSG00000028882; Expressed in 278 organ(s), highest expression level in mandibular prominence. 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:0005634; C:nucleus; IBA:GO_Central. 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 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:0035196; P:production of miRNAs involved in gene silencing by miRNA; 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; Complete proteome; Developmental protein; DNA-binding; KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; KW Protein phosphatase inhibitor; Reference proteome; Repressor; KW RNA-binding; Spliceosome; Transcription; Transcription regulation. FT CHAIN 1 351 Nuclear inhibitor of protein phosphatase FT 1. FT /FTId=PRO_0000071506. FT DOMAIN 49 101 FHA. {ECO:0000255|PROSITE- FT ProRule:PRU00086}. FT REGION 1 142 Interaction with CDC5L, SF3B1 and MELK. FT {ECO:0000250}. FT REGION 143 224 Interaction with EED. {ECO:0000250}. FT REGION 191 200 Involved in PP-1 inhibition. FT {ECO:0000250}. FT REGION 200 203 Involved in PP-1 binding. {ECO:0000250}. FT REGION 310 329 Interaction with EED. {ECO:0000250}. FT REGION 330 351 RNA-binding. {ECO:0000250}. FT REGION 331 337 Involved in PP-1 inhibition. FT {ECO:0000250}. FT MOTIF 185 209 Nuclear localization signal 1. FT {ECO:0000250}. FT MOTIF 210 240 Nuclear localization signal 2. FT {ECO:0000250}. FT COMPBIAS 2 5 Poly-Ala. FT COMPBIAS 331 334 Poly-Lys. FT MOD_RES 161 161 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q28147}. FT MOD_RES 178 178 Phosphoserine. FT {ECO:0000250|UniProtKB:Q28147}. FT MOD_RES 199 199 Phosphoserine. FT {ECO:0000250|UniProtKB:Q28147}. FT MOD_RES 204 204 Phosphoserine. FT {ECO:0000250|UniProtKB:Q28147}. FT MOD_RES 249 249 Phosphoserine. FT {ECO:0000250|UniProtKB:Q12972}. FT MOD_RES 264 264 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q12972}. FT MOD_RES 335 335 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q12972}. FT STRAND 7 9 {ECO:0000244|PDB:2JPE}. FT STRAND 18 20 {ECO:0000244|PDB:2JPE}. FT STRAND 28 41 {ECO:0000244|PDB:2JPE}. FT STRAND 51 53 {ECO:0000244|PDB:2JPE}. FT TURN 55 57 {ECO:0000244|PDB:2JPE}. FT STRAND 58 60 {ECO:0000244|PDB:2JPE}. FT STRAND 65 67 {ECO:0000244|PDB:2JPE}. FT STRAND 71 80 {ECO:0000244|PDB:2JPE}. FT STRAND 83 86 {ECO:0000244|PDB:2JPE}. FT STRAND 94 98 {ECO:0000244|PDB:2JPE}. FT STRAND 103 105 {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 //