PP2A_CAEEL
ID PP2A_CAEEL Reviewed; 318 AA.
AC G5EGK8;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Serine/threonine-protein phosphatase 2A catalytic subunit {ECO:0000305};
DE Short=PP2A {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000255|RuleBase:RU004273};
GN Name=let-92 {ECO:0000312|WormBase:F38H4.9};
GN ORFNames=F38H4.9 {ECO:0000312|WormBase:F38H4.9};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:BAJ07373.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH UNC-51 AND UNC-14,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAJ07373.1};
RX PubMed=20392746; DOI=10.1242/dev.050708;
RA Ogura K., Okada T., Mitani S., Gengyo-Ando K., Baillie D.L., Kohara Y.,
RA Goshima Y.;
RT "Protein phosphatase 2A cooperates with the autophagy-related kinase UNC-51
RT to regulate axon guidance in Caenorhabditis elegans.";
RL Development 137:1657-1667(2010).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=10521400; DOI=10.1101/gad.13.19.2562;
RA Sieburth D.S., Sundaram M., Howard R.M., Han M.;
RT "A PP2A regulatory subunit positively regulates Ras-mediated signaling
RT during Caenorhabditis elegans vulval induction.";
RL Genes Dev. 13:2562-2569(1999).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH RSA-1, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17218259; DOI=10.1016/j.cell.2006.10.050;
RA Schlaitz A.L., Srayko M., Dammermann A., Quintin S., Wielsch N.,
RA MacLeod I., de Robillard Q., Zinke A., Yates J.R. III, Mueller-Reichert T.,
RA Shevchenko A., Oegema K., Hyman A.A.;
RT "The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes
RT and regulates mitotic spindle assembly.";
RL Cell 128:115-127(2007).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH SZY-20; SUR-6 AND SAS-5, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21497766; DOI=10.1016/j.devcel.2011.03.007;
RA Song M.H., Liu Y., Anderson D.E., Jahng W.J., O'Connell K.F.;
RT "Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C.
RT elegans by controlling the levels of centriole assembly factors.";
RL Dev. Cell 20:563-571(2011).
CC -!- FUNCTION: Protein phosphatase which plays an essential role in early
CC embryonic cell division (PubMed:20392746, PubMed:17218259,
CC PubMed:21497766). Probably together with constant regulatory subunit
CC paa-1 and regulatory subunit sur-6, positively regulates centriole
CC duplication by preventing the degradation of sas-5 and kinase zyg-1
CC (PubMed:21497766). In addition, plays a role in the recruitment of sas-
CC 6 and maybe sas-5 to centrioles and may dephosphorylate sas-5 and zyg-1
CC negative regulator szy-20 (PubMed:21497766). During vulva development,
CC may play a role with regulatory subunits paa-1 and sur-6 in the
CC induction of vulva cell precursors by positively regulating let-60/Ras-
CC MAP kinase signaling, probably by promoting lin-45 activation
CC (PubMed:10521400). In association with regulatory subunit rsa-1 and
CC probably paa-1, regulates microtubule outgrowth from centrosomes and
CC mitotic spindle assembly ensuring the stability of kinetochore
CC microtubules (PubMed:17218259). Plays a negative role in axon guidance
CC probably by dephosphorylating unc-51, unc-14 and vab-8
CC (PubMed:20392746). {ECO:0000269|PubMed:10521400,
CC ECO:0000269|PubMed:17218259, ECO:0000269|PubMed:20392746,
CC ECO:0000269|PubMed:21497766}.
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:0000255|RuleBase:RU004273};
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:0000255|RuleBase:RU004273};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P36873};
CC Note=Binds 2 manganese ions per subunit.
CC {ECO:0000250|UniProtKB:P36873};
CC -!- SUBUNIT: Part of a complex consisting of a common heterodimeric core
CC enzyme, composed of catalytic subunit let-92 and constant regulatory
CC subunit paa-1, that associates with a variety of regulatory subunits
CC which confer distinct properties to the holoenzyme (PubMed:17218259).
CC Interacts with szy-20 and regulatory subunit sur-6 (PubMed:21497766).
CC Interacts with regulatory subunit rsa-1 (PubMed:17218259). May interact
CC with sas-5 (PubMed:21497766). Interacts with unc-51 and unc-14
CC (PubMed:20392746). {ECO:0000269|PubMed:17218259,
CC ECO:0000269|PubMed:20392746, ECO:0000269|PubMed:21497766}.
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:20392746}. Cell
CC projection, axon {ECO:0000269|PubMed:20392746}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:17218259}. Cytoplasm {ECO:0000269|PubMed:17218259}.
CC Note=Localizes to the margins of VD neuron growth cones and to small
CC transport vesicles (PubMed:20392746). During mitosis, localizes around
CC chromatin after the nuclear envelope breakdown (PubMed:17218259).
CC {ECO:0000269|PubMed:17218259, ECO:0000269|PubMed:20392746}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:20392746}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes severe embryonic
CC lethality (PubMed:10521400). Causes a failure to duplicate centrioles
CC resulting in the formation of monopolar spindles at the 2-cell
CC embryonic stage, a failure to align chromosomes at the metaphase plate,
CC delayed cell cycle progression and defects in mitotic exit including
CC failure to reform nuclei and decondense chromatin (PubMed:17218259,
CC PubMed:21497766). Also causes a reduction in centrosomal microtubules
CC (PubMed:17218259). In addition, recruitment of sas-6 to centriole is
CC impaired and sas-5 and zyg-1 protein levels are reduced
CC (PubMed:21497766). Few of the surviving animals show occasional defects
CC in vulva induction (PubMed:10521400). Partially suppresses multivulva
CC formation in a let-60 n1046 mutant background (PubMed:10521400).
CC {ECO:0000269|PubMed:10521400, ECO:0000269|PubMed:17218259,
CC ECO:0000269|PubMed:21497766}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AB108533; BAJ07373.1; -; mRNA.
DR EMBL; BX284604; CAB01174.1; -; Genomic_DNA.
DR PIR; T21975; T21975.
DR RefSeq; NP_502247.1; NM_069846.3.
DR AlphaFoldDB; G5EGK8; -.
DR SMR; G5EGK8; -.
DR ComplexPortal; CPX-1357; RSA centrosome-targeting complex.
DR ComplexPortal; CPX-1361; PP2A-RSA-1 phosphatase complex.
DR ComplexPortal; CPX-1366; PP2A-SUR-6 phosphatase complex.
DR ComplexPortal; CPX-1367; PP2A-PPTR-1 phosphatase complex.
DR ComplexPortal; CPX-1368; PP2A-PPTR-2 phosphatase complex.
DR ComplexPortal; CPX-1373; PP2A-F43B10.1 phosphatase complex.
DR ComplexPortal; CPX-1375; PP2A-F47B8.3 phosphatase complex.
DR ComplexPortal; CPX-1376; PP2A-T22D1.5 phosphatase complex.
DR IntAct; G5EGK8; 9.
DR STRING; 6239.F38H4.9.2; -.
DR EPD; G5EGK8; -.
DR PaxDb; G5EGK8; -.
DR PeptideAtlas; G5EGK8; -.
DR EnsemblMetazoa; F38H4.9.1; F38H4.9.1; WBGene00002363.
DR GeneID; 178117; -.
DR CTD; 178117; -.
DR WormBase; F38H4.9; CE10074; WBGene00002363; let-92.
DR eggNOG; KOG0371; Eukaryota.
DR GeneTree; ENSGT00550000074618; -.
DR HOGENOM; CLU_004962_0_5_1; -.
DR InParanoid; G5EGK8; -.
DR OMA; EGYNWGQ; -.
DR OrthoDB; 808922at2759; -.
DR PhylomeDB; G5EGK8; -.
DR Reactome; R-CEL-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR Reactome; R-CEL-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-CEL-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-CEL-198753; ERK/MAPK targets.
DR Reactome; R-CEL-202670; ERKs are inactivated.
DR Reactome; R-CEL-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-CEL-389513; CTLA4 inhibitory signaling.
DR Reactome; R-CEL-432142; Platelet sensitization by LDL.
DR Reactome; R-CEL-5673000; RAF activation.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-CEL-69231; Cyclin D associated events in G1.
DR Reactome; R-CEL-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-CEL-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR SignaLink; G5EGK8; -.
DR PRO; PR:G5EGK8; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002363; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0044295; C:axonal growth cone; IDA:WormBase.
DR GO; GO:0005813; C:centrosome; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IDA:ComplexPortal.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:WormBase.
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; IBA:GO_Central.
DR GO; GO:0098534; P:centriole assembly; IC:ComplexPortal.
DR GO; GO:0051299; P:centrosome separation; IMP:WormBase.
DR GO; GO:0051229; P:meiotic spindle disassembly; IMP:WormBase.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007100; P:mitotic centrosome separation; IMP:UniProtKB.
DR GO; GO:0007084; P:mitotic nuclear membrane reassembly; IMP:WormBase.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:WormBase.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0018985; P:pronuclear envelope synthesis; IMP:WormBase.
DR GO; GO:0040028; P:regulation of vulval development; IC:ComplexPortal.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoskeleton; Hydrolase; Manganese;
KW Metal-binding; Protein phosphatase; Reference proteome.
FT CHAIN 1..318
FT /note="Serine/threonine-protein phosphatase 2A catalytic
FT subunit"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437751"
FT ACT_SITE 127
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 66
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 68
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 94
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 94
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 126
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 176
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 250
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P36873"
SQ SEQUENCE 318 AA; 36302 MW; F159BF8EF35A855E CRC64;
MAAAPPSADP LDKALIVDVD QWIEQLYECK PLSENQVKTL CEKAKEILEK EPNVQEVRCP
VTVCGDVHGQ FHDLMELFKM GGKSPDTNYL FMGDYVDRGY YSVETVSLLV CLKIRYKDRV
TLLRGNHESR QITQVYGFYD ECLRKYGNSN VWKYFTDLFD CFPLTALVDG QIFCLHGGLS
PSIDTLDHIR ALDRIQEVPH EGPMCDLLWS DPDDRGGWGI SPRGAGYTFG QDISETFNHS
NGLTLISRAH QLVMEGYNWS HDRNVVTVFS APNYCYRCGN QAAMVELDDD LKYSFLQFDP
APRRGEPHVT RRTPDYFL
