PP1R8_BOVIN
ID PP1R8_BOVIN Reviewed; 351 AA.
AC Q28147;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 134.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, PROTEIN SEQUENCE OF
RP 163-171 AND 196-208, BLOCKAGE OF N-TERMINUS, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT SER-199.
RC TISSUE=Thymus;
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 [2]
RP PROTEIN SEQUENCE OF 152-191 AND 197-221, CHARACTERIZATION, PHOSPHORYLATION
RP AT THR-161; SER-178; SER-199 AND SER-204, LACK OF PHOSPHORYLATION AT
RP THR-202 AND THR-346, AND MASS SPECTROMETRY.
RX PubMed=9407077; DOI=10.1074/jbc.272.52.32972;
RA Vulsteke V., Beullens M., Waelkens E., Stalmans W., Bollen M.;
RT "Properties and phosphorylation sites of baculovirus-expressed nuclear
RT inhibitor of protein phosphatase-1 (NIPP-1).";
RL J. Biol. Chem. 272:32972-32978(1997).
RN [3]
RP RNA-BINDING, AND FUNCTION.
RX PubMed=9268347; DOI=10.1074/jbc.272.35.22067;
RA Jagiello I., Beullens M., Vulsteke V., Wera S., Sohlberg B., Stalmans W.,
RA von Gabain A., Bollen M.;
RT "NIPP-1, a nuclear inhibitory subunit of protein phosphatase-1, has RNA-
RT binding properties.";
RL J. Biol. Chem. 272:22067-22071(1997).
RN [4]
RP DOMAIN PP-1 BINDING, SYNTHESIS OF PEPTIDES IN THE 141-230 REGION, AND
RP PHOSPHORYLATION AT SER-204.
RX PubMed=10318819; DOI=10.1074/jbc.274.20.14053;
RA Beullens M., Van Eynde A., Vulsteke V., Connor J., Shenolikar S.,
RA Stalmans W., Bollen M.;
RT "Molecular determinants of nuclear protein phosphatase-1 regulation by
RT NIPP-1.";
RL J. Biol. Chem. 274:14053-14061(1999).
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 {ECO:0000269|PubMed:9268347}.
CC -!- SUBUNIT: Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts
CC with EED. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1.
CC Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus speckle
CC {ECO:0000250}. Note=Mainly, but not exclusively, nuclear.
CC {ECO:0000269|PubMed:7499293}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q28147-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q28147-2; Sequence=VSP_005118;
CC -!- DOMAIN: Has a basic N- and C-terminal and an acidic central domain.
CC {ECO:0000269|PubMed:10318819}.
CC -!- DOMAIN: The FHA domain mediates interactions with threonine-
CC phosphorylated MELK. {ECO:0000250}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Inactivated by phosphorylation on Ser-199 or Ser-204.
CC {ECO:0000305|PubMed:10318819, ECO:0000305|PubMed:7499293,
CC ECO:0000305|PubMed:9407077}.
CC -!- MASS SPECTROMETRY: Mass=38520; Method=Electrospray; Note=Expressed in
CC baculovirus.; Evidence={ECO:0000269|PubMed:9407077};
CC -!- MISCELLANEOUS: A synthetic peptide, NIPP-1(191-200), is able to inhibit
CC PP-1. Alanine substitution of Val-201 and Phe-203 in NIPP-1(191-210)
CC prevents PP-1 binding (far-western assay) but do not affect PP-1
CC inhibition. Phosphorylation of Ser-199 or Ser-204 prevents PP-1 binding
CC (far-western assay) and reduces PP-1 inhibition.
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DR EMBL; Z50748; CAA90625.1; -; mRNA.
DR PIR; I46033; I46033.
DR RefSeq; NP_777007.1; NM_174582.2. [Q28147-1]
DR AlphaFoldDB; Q28147; -.
DR BMRB; Q28147; -.
DR SMR; Q28147; -.
DR BioGRID; 159581; 4.
DR DIP; DIP-438N; -.
DR STRING; 9913.ENSBTAP00000005043; -.
DR iPTMnet; Q28147; -.
DR PaxDb; Q28147; -.
DR PRIDE; Q28147; -.
DR GeneID; 282319; -.
DR KEGG; bta:282319; -.
DR CTD; 5511; -.
DR eggNOG; KOG1880; Eukaryota.
DR InParanoid; Q28147; -.
DR OrthoDB; 955935at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016607; C:nuclear speck; 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:0004865; F:protein serine/threonine phosphatase inhibitor activity; IBA:GO_Central.
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 Alternative splicing; Direct protein sequencing; DNA-binding;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Protein phosphatase inhibitor; Reference proteome; Repressor; RNA-binding;
KW Spliceosome; Transcription; Transcription regulation.
FT CHAIN 1..351
FT /note="Nuclear inhibitor of protein phosphatase 1"
FT /id="PRO_0000071504"
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 REGION 200..203
FT /note="Involved in PP-1 binding"
FT REGION 310..329
FT /note="Interaction with EED"
FT /evidence="ECO:0000250"
FT REGION 316..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 SITE 202
FT /note="Not phosphorylated"
FT /evidence="ECO:0000269|PubMed:9407077"
FT SITE 346
FT /note="Not phosphorylated"
FT /evidence="ECO:0000269|PubMed:9407077"
FT MOD_RES 161
FT /note="Phosphothreonine; by CK2; in vitro"
FT /evidence="ECO:0000269|PubMed:9407077"
FT MOD_RES 178
FT /note="Phosphoserine; by PKA; in vitro"
FT /evidence="ECO:0000269|PubMed:9407077"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:7499293,
FT ECO:0000269|PubMed:9407077"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:10318819,
FT ECO:0000305|PubMed:9407077"
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 VAR_SEQ 1..142
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_005118"
SQ SEQUENCE 351 AA; 38521 MW; 7CD5F6E162A66210 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
PGSLVLEESG SRRMQNFAFS GGLYGGLPPT HSEAGSQPHG IHGTALIGGL PMPYPNLAPD
VDLTPVVPSA VNMNPAPNPA VYNPEAVNEP KKKKYAKEAW PGKKPTPSLL I
