PP4R1_HUMAN
ID PP4R1_HUMAN Reviewed; 950 AA.
AC Q8TF05; Q99774; Q9UNQ7;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Serine/threonine-protein phosphatase 4 regulatory subunit 1;
GN Name=PPP4R1; Synonyms=MEG1, PP4R1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBUNIT.
RC TISSUE=Neuroepithelium;
RX PubMed=10026142; DOI=10.1074/jbc.274.9.5339;
RA Kloeker S., Wadzinski B.E.;
RT "Purification and identification of a novel subunit of protein
RT serine/threonine phosphatase 4.";
RL J. Biol. Chem. 274:5339-5347(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=11729228; DOI=10.1681/asn.v12122601;
RA Wada T., Miyata T., Inagi R., Nangaku M., Wagatsuma M., Suzuki D.,
RA Wadzinski B.E., Okubo K., Kurokawa K.;
RT "Cloning and characterization of a novel subunit of protein
RT serine/threonine phosphatase 4 from mesangial cells.";
RL J. Am. Soc. Nephrol. 12:2601-2608(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 571-950 (ISOFORMS 1/2).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human hypothetical 19.5 kDa protein gene.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 778-950 (ISOFORMS 1/2).
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [7]
RP INTERACTION WITH HDAC3, AND FUNCTION OF THE PPP4C-PPP4R1 COMPLEX.
RX PubMed=15805470; DOI=10.1101/gad.1286005;
RA Zhang X., Ozawa Y., Lee H., Wen Y.D., Tan T.H., Wadzinski B.E., Seto E.;
RT "Histone deacetylase 3 (HDAC3) activity is regulated by interaction with
RT protein serine/threonine phosphatase 4.";
RL Genes Dev. 19:827-839(2005).
RN [8]
RP IDENTIFICATION IN THE PPP4C-PPP4R1 COMPLEX.
RX PubMed=18614045; DOI=10.1016/j.molcel.2008.05.016;
RA Chowdhury D., Xu X., Zhong X., Ahmed F., Zhong J., Liao J., Dykxhoorn D.M.,
RA Weinstock D.M., Pfeifer G.P., Lieberman J.;
RT "A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA
RT replication.";
RL Mol. Cell 31:33-46(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-935, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Regulatory subunit of serine/threonine-protein phosphatase 4.
CC May play a role in regulation of cell division in renal glomeruli. The
CC PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and
CC regulation of HDAC3. {ECO:0000269|PubMed:15805470}.
CC -!- SUBUNIT: Serine/threonine-protein phosphatase 4 (PP4) occurs in
CC different assemblies of the catalytic and one or more regulatory
CC subunits. Component of the PP4 complex PPP4C-PPP4R1. Interacts with
CC HDAC3. {ECO:0000269|PubMed:10026142, ECO:0000269|PubMed:11729228,
CC ECO:0000269|PubMed:15805470, ECO:0000269|PubMed:18614045}.
CC -!- INTERACTION:
CC Q8TF05; P60510: PPP4C; NbExp=8; IntAct=EBI-1056262, EBI-1046072;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PP4Rmeg;
CC IsoId=Q8TF05-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TF05-2; Sequence=VSP_009469;
CC -!- TISSUE SPECIFICITY: Widely expressed with high expression in cultured
CC mesangial cells. Isoform 1 and isoform 2 are expressed in renal
CC tissues. {ECO:0000269|PubMed:11729228}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD43008.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF111106; AAD09818.1; -; mRNA.
DR EMBL; AF200478; AAL78298.1; -; mRNA.
DR EMBL; AP000902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001381; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC060829; AAH60829.1; -; mRNA.
DR EMBL; AF100744; AAD43008.1; ALT_INIT; mRNA.
DR EMBL; U79267; AAB50211.1; -; mRNA.
DR CCDS; CCDS42412.1; -. [Q8TF05-1]
DR CCDS; CCDS42413.1; -. [Q8TF05-2]
DR RefSeq; NP_001035847.1; NM_001042388.2. [Q8TF05-1]
DR RefSeq; NP_005125.1; NM_005134.3. [Q8TF05-2]
DR AlphaFoldDB; Q8TF05; -.
DR BioGRID; 115310; 57.
DR ComplexPortal; CPX-1842; PPP4C-PPP4R1 protein phosphatase 4 complex.
DR IntAct; Q8TF05; 26.
DR MINT; Q8TF05; -.
DR STRING; 9606.ENSP00000383402; -.
DR GlyGen; Q8TF05; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TF05; -.
DR MetOSite; Q8TF05; -.
DR PhosphoSitePlus; Q8TF05; -.
DR BioMuta; PPP4R1; -.
DR DMDM; 44888283; -.
DR EPD; Q8TF05; -.
DR jPOST; Q8TF05; -.
DR MassIVE; Q8TF05; -.
DR MaxQB; Q8TF05; -.
DR PaxDb; Q8TF05; -.
DR PeptideAtlas; Q8TF05; -.
DR PRIDE; Q8TF05; -.
DR ProteomicsDB; 74532; -. [Q8TF05-1]
DR ProteomicsDB; 74533; -. [Q8TF05-2]
DR Antibodypedia; 21930; 109 antibodies from 24 providers.
DR DNASU; 9989; -.
DR Ensembl; ENST00000400555.7; ENSP00000383401.3; ENSG00000154845.16. [Q8TF05-2]
DR Ensembl; ENST00000400556.8; ENSP00000383402.3; ENSG00000154845.16. [Q8TF05-1]
DR GeneID; 9989; -.
DR KEGG; hsa:9989; -.
DR MANE-Select; ENST00000400556.8; ENSP00000383402.3; NM_001042388.3; NP_001035847.1.
DR UCSC; uc002kod.3; human. [Q8TF05-1]
DR CTD; 9989; -.
DR DisGeNET; 9989; -.
DR GeneCards; PPP4R1; -.
DR HGNC; HGNC:9320; PPP4R1.
DR HPA; ENSG00000154845; Low tissue specificity.
DR MIM; 604908; gene.
DR neXtProt; NX_Q8TF05; -.
DR OpenTargets; ENSG00000154845; -.
DR PharmGKB; PA33684; -.
DR VEuPathDB; HostDB:ENSG00000154845; -.
DR eggNOG; KOG0211; Eukaryota.
DR GeneTree; ENSGT00950000183066; -.
DR HOGENOM; CLU_009128_1_1_1; -.
DR InParanoid; Q8TF05; -.
DR OMA; AIMALQM; -.
DR OrthoDB; 249499at2759; -.
DR PhylomeDB; Q8TF05; -.
DR TreeFam; TF105560; -.
DR PathwayCommons; Q8TF05; -.
DR SignaLink; Q8TF05; -.
DR BioGRID-ORCS; 9989; 22 hits in 1089 CRISPR screens.
DR ChiTaRS; PPP4R1; human.
DR GeneWiki; PPP4R1; -.
DR GenomeRNAi; 9989; -.
DR Pharos; Q8TF05; Tbio.
DR PRO; PR:Q8TF05; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q8TF05; protein.
DR Bgee; ENSG00000154845; Expressed in sperm and 202 other tissues.
DR ExpressionAtlas; Q8TF05; baseline and differential.
DR Genevisible; Q8TF05; HS.
DR GO; GO:0030289; C:protein phosphatase 4 complex; ISS:UniProtKB.
DR GO; GO:0019888; F:protein phosphatase regulator activity; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000357; HEAT.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR031087; PP4R1.
DR InterPro; IPR033461; WRNPLPNID.
DR PANTHER; PTHR10648:SF8; PTHR10648:SF8; 1.
DR Pfam; PF02985; HEAT; 2.
DR Pfam; PF15017; WRNPLPNID; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..950
FT /note="Serine/threonine-protein phosphatase 4 regulatory
FT subunit 1"
FT /id="PRO_0000071527"
FT REPEAT 1..25
FT /note="HEAT 1"
FT REPEAT 26..63
FT /note="HEAT 2"
FT REPEAT 65..81
FT /note="HEAT 3"
FT REPEAT 82..119
FT /note="HEAT 4"
FT REPEAT 127..164
FT /note="HEAT 5"
FT REPEAT 168..206
FT /note="HEAT 6"
FT REPEAT 208..246
FT /note="HEAT 7"
FT REPEAT 248..285
FT /note="HEAT 8"
FT REPEAT 287..324
FT /note="HEAT 9"
FT REPEAT 505..542
FT /note="HEAT 10"
FT REPEAT 568..606
FT /note="HEAT 11"
FT REPEAT 698..734
FT /note="HEAT 12"
FT REPEAT 799..837
FT /note="HEAT 13"
FT REPEAT 861..898
FT /note="HEAT 14"
FT REGION 326..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 935
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 18..35
FT /note="FGVDDYSSESDVIIIPSA -> S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10026142,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_009469"
FT VARIANT 43
FT /note="E -> K (in dbSNP:rs1056191)"
FT /id="VAR_017807"
FT VARIANT 470
FT /note="I -> V (in dbSNP:rs329003)"
FT /id="VAR_017808"
FT VARIANT 593
FT /note="S -> N (in dbSNP:rs2306134)"
FT /id="VAR_051748"
FT VARIANT 595
FT /note="S -> N (in dbSNP:rs2306134)"
FT /id="VAR_017809"
SQ SEQUENCE 950 AA; 107004 MW; E1392E6BAD3B58CB CRC64;
MADLSLLQED LQEDADGFGV DDYSSESDVI IIPSALDFVS QDEMLTPLGR LDKYAASENI
FNRQMVARSL LDTLREVCDD ERDCIAVLER ISRLADDSEP TVRAELMEQV PHIALFCQEN
RPSIPYAFSK FLLPIVVRYL ADQNNQVRKT SQAALLALLE QELIERFDVE TKVCPVLIEL
TAPDSNDDVK TEAVAIMCKM APMVGKDITE RLILPRFCEM CCDCRMFHVR KVCAANFGDI
CSVVGQQATE EMLLPRFFQL CSDNVWGVRK ACAECFMAVS CATCQEIRRT KLSALFINLI
SDPSRWVRQA AFQSLGPFIS TFANPSSSGQ YFKEESKSSE EMSVENKNRT RDQEAPEDVQ
VRPEDTPSDL SVSNSSVILE NTMEDHAAEA SGKPLGEISV PLDSSLLCTL SSESHQEAAS
NENDKKPGNY KSMLRPEVGT TSQDSALLDQ ELYNSFHFWR TPLPEIDLDI ELEQNSGGKP
SPEGPEEESE GPVPSSPNIT MATRKELEEM IENLEPHIDD PDVKAQVEVL SAALRASSLD
AHEETISIEK RSDLQDELDI NELPNCKINQ EDSVPLISDA VENMDSTLHY IHSDSDLSNN
SSFSPDEERR TKVQDVVPQA LLDQYLSMTD PSRAQTVDTE IAKHCAYSLP GVALTLGRQN
WHCLRETYET LASDMQWKVR RTLAFSIHEL AVILGDQLTA ADLVPIFNGF LKDLDEVRIG
VLKHLHDFLK LLHIDKRREY LYQLQEFLVT DNSRNWRFRA ELAEQLILLL ELYSPRDVYD
YLRPIALNLC ADKVSSVRWI SYKLVSEMVK KLHAATPPTF GVDLINELVE NFGRCPKWSG
RQAFVFVCQT VIEDDCLPMD QFAVHLMPHL LTLANDRVPN VRVLLAKTLR QTLLEKDYFL
ASASCHQEAV EQTIMALQMD RDSDVKYFAS IHPASTKISE DAMSTASSTY
