2AAA_CAEEL
ID 2AAA_CAEEL Reviewed; 590 AA.
AC Q09543;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Probable serine/threonine-protein phosphatase PP2A regulatory subunit;
DE AltName: Full=Protein phosphatase PP2A regulatory subunit A;
GN Name=paa-1; ORFNames=F48E8.5;
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 [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 [2]
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 [3]
RP FUNCTION, AND INTERACTION WITH RSA-1.
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 [4]
RP FUNCTION.
RC STRAIN=Bristol N2;
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 [5]
RP FUNCTION, AND DISRUPTION 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).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23336080; DOI=10.1242/bio.20122956;
RA Lange K.I., Heinrichs J., Cheung K., Srayko M.;
RT "Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate
RT regulatory RSA-1/B'' subunit targeting of PP2A to centrosomes in C.
RT elegans.";
RL Biol. Open 2:88-94(2013).
CC -!- FUNCTION: Acts as a scaffolding protein for phosphatase let-92 and its
CC regulatory subunits (Probable). Probably together with let-92 and
CC regulatory subunit sur-6, regulates centriole duplication, microtubule
CC outgrowth and mitotic spindle stability during early embryonic cell
CC division by preventing the degradation of sas-5 and kinase zyg-1
CC (PubMed:23336080, PubMed:17218259). During vulva development, may play
CC a role with phosphatase let-92 and regulatory subunit 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). Plays a positive role in axon guidance probably by
CC inhibiting phosphatase let-92 (PubMed:20392746).
CC {ECO:0000269|PubMed:10521400, ECO:0000269|PubMed:20392746,
CC ECO:0000269|PubMed:23336080, ECO:0000303|PubMed:17218259,
CC ECO:0000305|PubMed:21497766}.
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 PubMed:21497766). Interacts with rsa-1 (PubMed:17218259).
CC {ECO:0000269|PubMed:17218259, ECO:0000305|PubMed:21497766}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:23336080}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:23336080}. Note=Localizes to
CC P granules in embryonic cells. {ECO:0000269|PubMed:23336080}.
CC -!- DOMAIN: Each HEAT repeat appears to consist of two alpha helices joined
CC by a hydrophilic region, the intrarepeat loop. The repeat units may be
CC arranged laterally to form a rod-like structure.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes severe embryonic
CC lethality (PubMed:10521400, PubMed:23336080). Causes a failure to
CC duplicate centrioles resulting in the formation of monopolar spindles
CC at the 2-cell embryonic stage (PubMed:21497766, PubMed:23336080). sas-5
CC protein levels are reduced in embryos (PubMed:21497766). The few
CC surviving animals lack a vulva resulting from defects in vulva cell
CC induction, vulva precursor cell (VPC) generation and in vulval
CC execution linage (PubMed:10521400). Partially suppresses multivulva
CC formation in a let-60 n1046 mutant background (PubMed:10521400).
CC {ECO:0000269|PubMed:10521400, ECO:0000269|PubMed:21497766,
CC ECO:0000269|PubMed:23336080}.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit A family.
CC {ECO:0000305}.
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DR EMBL; FO081421; CCD71513.1; -; Genomic_DNA.
DR PIR; T16411; T16411.
DR RefSeq; NP_498162.2; NM_065761.4.
DR AlphaFoldDB; Q09543; -.
DR SMR; Q09543; -.
DR BioGRID; 40979; 15.
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 DIP; DIP-26927N; -.
DR IntAct; Q09543; 7.
DR STRING; 6239.F48E8.5.2; -.
DR iPTMnet; Q09543; -.
DR EPD; Q09543; -.
DR PaxDb; Q09543; -.
DR PeptideAtlas; Q09543; -.
DR EnsemblMetazoa; F48E8.5.1; F48E8.5.1; WBGene00003901.
DR GeneID; 175750; -.
DR KEGG; cel:CELE_F48E8.5; -.
DR UCSC; F48E8.5.2; c. elegans.
DR CTD; 175750; -.
DR WormBase; F48E8.5; CE30997; WBGene00003901; paa-1.
DR eggNOG; KOG0211; Eukaryota.
DR GeneTree; ENSGT00950000183066; -.
DR HOGENOM; CLU_015533_2_1_1; -.
DR InParanoid; Q09543; -.
DR OMA; SSLCMSW; -.
DR OrthoDB; 447572at2759; -.
DR PhylomeDB; Q09543; -.
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; Q09543; -.
DR PRO; PR:Q09543; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00003901; Expressed in embryo and 4 other tissues.
DR GO; GO:0005813; C:centrosome; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IDA:WormBase.
DR GO; GO:0005635; C:nuclear envelope; IDA:WormBase.
DR GO; GO:0043186; C:P granule; IDA:WormBase.
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:0019888; F:protein phosphatase regulator activity; IBA:GO_Central.
DR GO; GO:0098534; P:centriole assembly; IC:ComplexPortal.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:ComplexPortal.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0040028; P:regulation of vulval development; IC:ComplexPortal.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000357; HEAT.
DR InterPro; IPR021133; HEAT_type_2.
DR Pfam; PF02985; HEAT; 2.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 8.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Reference proteome; Repeat.
FT CHAIN 1..590
FT /note="Probable serine/threonine-protein phosphatase PP2A
FT regulatory subunit"
FT /id="PRO_0000071407"
FT REPEAT 37..73
FT /note="HEAT 1"
FT REPEAT 74..111
FT /note="HEAT 2"
FT REPEAT 113..150
FT /note="HEAT 3"
FT REPEAT 151..188
FT /note="HEAT 4"
FT REPEAT 189..227
FT /note="HEAT 5"
FT REPEAT 228..266
FT /note="HEAT 6"
FT REPEAT 267..305
FT /note="HEAT 7"
FT REPEAT 306..344
FT /note="HEAT 8"
FT REPEAT 349..387
FT /note="HEAT 9"
FT REPEAT 388..426
FT /note="HEAT 10"
FT REPEAT 427..465
FT /note="HEAT 11"
FT REPEAT 466..504
FT /note="HEAT 12"
FT REPEAT 505..543
FT /note="HEAT 13"
FT REPEAT 544..582
FT /note="HEAT 14"
SQ SEQUENCE 590 AA; 66149 MW; E9B6F7DFFEB973E2 CRC64;
MSVVEEATDD ALYPIAVLID ELRNEDVTLR LNSIRKLSTI ALALGVERTR NELIQFLTDT
IYDEDEVLLV LAEQLGNFTP LVGGPDHVHC LLLPLENLAT VEETVVRDKA VESLRKIADK
HSSASLEEHF VPMLRRLATG DWFTSRTSAC GLFSVVYPRV SPAIKSELKS MFRTLCRDDT
PMVRRAAAAK LGEFAKVFEK TAVIEGLHSS LTDLHVDEQD SVRLLTVESA IAFGTLLDKA
NKKKLIEPIL IELFDDKSWR VRYMVAEKLI EIQNVLGEDM DTTHLVNMYT NLLKDPEGEV
RCAATQRLQE FALNLPEDKR QNIICNSLLN VAKELVTDGN QLVKSELAGV IMGLAPLIGK
EQTVSELLPI YMQLLNDQTP EVRLNIISSL DKVNEVIGAA QLSTSLLPAI VGLAEDGKWR
VRLAIVQFMP LLASQLGQEF FDEKLLPLCL NWLTDHVFSI REASTLIMKE LTQKFGGQWA
STNIVPKMQK LQKDTNYLQR MTCLFCLNTL SEAMTQEQIL KEIMPIVKDL VEDDVPNVRF
NAAKSLKRIG KNLTPSTLTS EVKPLLEKLG KDSDFDVRYF SEEAKNSLGL
