ID   PP4C1_CAEEL             Reviewed;         333 AA.
AC   Q9XW79; Q966Q4;
DT   04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Serine/threonine-protein phosphatase 4 catalytic subunit 1;
DE            Short=PP4C-1;
DE            EC=3.1.3.16 {ECO:0000250|UniProtKB:P60510};
GN   Name=pph-4.1 {ECO:0000303|PubMed:11896188,
GN   ECO:0000312|WormBase:Y75B8A.30};
GN   ORFNames=Y75B8A.30 {ECO:0000312|WormBase:Y75B8A.30};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP   STAGE, AND DISRUPTION PHENOTYPE.
RC   STRAIN=Bristol N2;
RX   PubMed=11896188; DOI=10.1242/jcs.115.7.1403;
RA   Sumiyoshi E., Sugimoto A., Yamamoto M.;
RT   "Protein phosphatase 4 is required for centrosome maturation in mitosis and
RT   sperm meiosis in C. elegans.";
RL   J. Cell Sci. 115:1403-1410(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [3]
RP   FUNCTION, INTERACTION WITH MEI-1, AND DISRUPTION PHENOTYPE.
RX   PubMed=19087961; DOI=10.1534/genetics.108.096016;
RA   Han X., Gomes J.E., Birmingham C.L., Pintard L., Sugimoto A., Mains P.E.;
RT   "The role of protein phosphatase 4 in regulating microtubule severing in
RT   the Caenorhabditis elegans embryo.";
RL   Genetics 181:933-943(2009).
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-107 AND ARG-262.
RX   PubMed=25340746; DOI=10.1371/journal.pgen.1004638;
RA   Sato-Carlton A., Li X., Crawley O., Testori S., Martinez-Perez E.,
RA   Sugimoto A., Carlton P.M.;
RT   "Protein phosphatase 4 promotes chromosome pairing and synapsis, and
RT   contributes to maintaining crossover competence with increasing age.";
RL   PLoS Genet. 10:E1004638-E1004638(2014).
CC   -!- FUNCTION: Protein phosphatase which plays an essential role in meiosis
CC       and in early embryonic mitosis (PubMed:11896188, PubMed:25340746).
CC       During spermatocyte meiosis and the first embryonic mitosis, regulates
CC       centrosome maturation, and thus spindle formation, by recruiting some
CC       of the components of the pericentriolar material (PCM)
CC       (PubMed:11896188). During oocyte meiosis I, regulates meiotic
CC       chromosome dynamics including synapsis-independent chromosome pairing,
CC       restriction of synapsis to homologous chromosomes, programmed DNA
CC       double-strand break initiation and crossover formation resulting in
CC       chiasma formation (PubMed:11896188, PubMed:25340746). During oocyte
CC       meiosis II and probably together with regulatory subunit ppfr-1, may
CC       regulate microtubule severing by dephosphorylating and activating mei-
CC       1, a component of the katanin microtubule severing complex
CC       (PubMed:19087961). {ECO:0000269|PubMed:11896188,
CC       ECO:0000269|PubMed:19087961, ECO:0000269|PubMed:25340746}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC         Evidence={ECO:0000250|UniProtKB:P60510};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC         Evidence={ECO:0000250|UniProtKB:P60510};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P67775};
CC       Note=Binds 2 manganese ions per subunit.
CC       {ECO:0000250|UniProtKB:P67775};
CC   -!- SUBUNIT: Serine/threonine-protein phosphatase 4 (PP4) occurs in
CC       different assemblies of the catalytic and one or more regulatory
CC       subunits (By similarity). The regulatory subunits are likely to be
CC       ppfr-1, ppfr-2, ppfr-4 and smk-1 (PubMed:19087961). Interacts with mei-
CC       1 (PubMed:19087961). {ECO:0000250|UniProtKB:P60510,
CC       ECO:0000269|PubMed:19087961, ECO:0000305|PubMed:19087961}.
CC   -!- INTERACTION:
CC       Q9XW79; Q9N4E9: ppfr-4; NbExp=3; IntAct=EBI-331742, EBI-331766;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11896188}.
CC       Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC       {ECO:0000269|PubMed:11896188}. Note=Localizes at centrosomes from
CC       prophase to telophase but not during interphase. Also localizes to the
CC       cytoplasm throughout the cell cycle. {ECO:0000269|PubMed:11896188}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in embryos (at protein level).
CC       {ECO:0000269|PubMed:11896188}.
CC   -!- PTM: Methylation at the C-terminal Leu-333 is critical for interactions
CC       with regulatory subunits. {ECO:0000250|UniProtKB:P60510}.
CC   -!- DISRUPTION PHENOTYPE: Severe embryonic lethality associated with a high
CC       incidence of male progeny (PubMed:25340746). RNAi-mediated knockdown
CC       causes 20 percent embryonic lethality and 18 percent larval lethality
CC       (PubMed:11896188). Abnormal meiosis and mitosis leading to defects in
CC       gametogenesis and embryogenesis (PubMed:11896188, PubMed:25340746). In
CC       spermatocytes, defects in the organization of astral microtubules
CC       (PubMed:11896188). In oocyte meiosis I, defects in autosomal chromosome
CC       pairing resulting from abnormal synapsis (PubMed:25340746). In embryos,
CC       RNAi-mediated knockdown causes abnormal mitosis due to defects in
CC       astral microtubules organization (PubMed:11896188). In a gain of
CC       function mei-1 (ct46) or in mel-26 (ct61sb4) mutant background, RNAi-
CC       mediated knockdown partially rescues embryonic lethality without
CC       affecting mei-1 expression levels and localization (PubMed:19087961).
CC       {ECO:0000269|PubMed:11896188, ECO:0000269|PubMed:19087961,
CC       ECO:0000269|PubMed:25340746}.
CC   -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-4 (PP-X)
CC       subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB63947.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB070573; BAB63947.1; ALT_INIT; mRNA.
DR   EMBL; AL033514; CAA22090.1; -; Genomic_DNA.
DR   PIR; T27390; T27390.
DR   RefSeq; NP_499603.1; NM_067202.5.
DR   AlphaFoldDB; Q9XW79; -.
DR   SMR; Q9XW79; -.
DR   BioGRID; 41836; 15.
DR   DIP; DIP-24807N; -.
DR   IntAct; Q9XW79; 7.
DR   STRING; 6239.Y75B8A.30.1; -.
DR   EPD; Q9XW79; -.
DR   PaxDb; 6239-Y75B8A-30; -.
DR   PeptideAtlas; Q9XW79; -.
DR   EnsemblMetazoa; Y75B8A.30.1; Y75B8A.30.1; WBGene00004085.
DR   GeneID; 176657; -.
DR   KEGG; cel:CELE_Y75B8A.30; -.
DR   UCSC; Y75B8A.30; c. elegans.
DR   AGR; WB:WBGene00004085; -.
DR   WormBase; Y75B8A.30; CE23041; WBGene00004085; pph-4.1.
DR   eggNOG; KOG0372; Eukaryota.
DR   GeneTree; ENSGT00930000151040; -.
DR   HOGENOM; CLU_004962_8_1_1; -.
DR   InParanoid; Q9XW79; -.
DR   OMA; QSTMPID; -.
DR   OrthoDB; 19833at2759; -.
DR   PhylomeDB; Q9XW79; -.
DR   SignaLink; Q9XW79; -.
DR   PRO; PR:Q9XW79; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00004085; Expressed in pharyngeal muscle cell (C elegans) and 4 other cell types or tissues.
DR   GO; GO:0005813; C:centrosome; IDA:WormBase.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:WormBase.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0051026; P:chiasma assembly; IMP:UniProtKB.
DR   GO; GO:0016311; P:dephosphorylation; ISS:WormBase.
DR   GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR   GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:UniProtKB.
DR   GO; GO:0051321; P:meiotic cell cycle; IMP:WormBase.
DR   GO; GO:1905261; P:regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination; IMP:UniProtKB.
DR   CDD; cd07415; MPP_PP2A_PP4_PP6; 1.
DR   Gene3D; 3.60.21.10; -; 1.
DR   InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR   InterPro; IPR029052; Metallo-depent_PP-like.
DR   InterPro; IPR047129; PPA2-like.
DR   InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR   PANTHER; PTHR45619; SERINE/THREONINE-PROTEIN PHOSPHATASE PP2A-RELATED; 1.
DR   PANTHER; PTHR45619:SF8; SERINE_THREONINE-PROTEIN PHOSPHATASE 4 CATALYTIC SUBUNIT; 1.
DR   Pfam; PF00149; Metallophos; 1.
DR   PRINTS; PR00114; STPHPHTASE.
DR   SMART; SM00156; PP2Ac; 1.
DR   SUPFAM; SSF56300; Metallo-dependent phosphatases; 1.
DR   PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Hydrolase; Manganese;
KW   Meiosis; Metal-binding; Methylation; Mitosis; Protein phosphatase;
KW   Reference proteome.
FT   CHAIN           1..333
FT                   /note="Serine/threonine-protein phosphatase 4 catalytic
FT                   subunit 1"
FT                   /id="PRO_0000353210"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..27
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        140
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         79
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         81
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         107
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         107
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         139
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         189
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         264
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   MOD_RES         333
FT                   /note="Leucine methyl ester"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   MUTAGEN         107
FT                   /note="D->A: Probable loss of catalytic activity. Severe
FT                   loss of bivalent chromosome formation in diakinetic
FT                   oocytes."
FT                   /evidence="ECO:0000269|PubMed:25340746"
FT   MUTAGEN         262
FT                   /note="R->L: Probable loss of catalytic activity. Severe
FT                   loss of bivalent chromosome formation in diakinetic
FT                   oocytes."
FT                   /evidence="ECO:0000269|PubMed:25340746"
SQ   SEQUENCE   333 AA;  37359 MW;  7C7EA2177E45AA52 CRC64;
     MALACTDSAN STFSRVDSPT SGPSDQLTTH DLDRHIEKLM RCELIAEQDV KTLCAKAREI
     LAEEGNVQVI DSPVTICGDI HGQFYDLMEL FKVGGPVPNT NYLFLGDFVD RGFYSVETFL
     LLLALKARYP DRMMLIRGNH ESRQITQVYG FYDECLRKYG NASVWKHCTE VFDYLSLAAV
     IDGKVFCVHG GLSPSISTMD QIRVIDRKQE VPHDGPMCDL LWSDPEEGNV GWGLSPRGAG
     YLFGADASKT FCETNGVDLI CRAHQLVMEG YKWHFNEKVL TVWSAPNYCY RCGNVAAILE
     LDENLNKEFT IFEAAPQENR GAPAKKPHAD YFL
//