ID   PPP6_MOUSE              Reviewed;         305 AA.
AC   Q9CQR6; A2ASL7;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 157.
DE   RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit {ECO:0000305};
DE            Short=PP6C {ECO:0000303|PubMed:26868000};
DE            EC=3.1.3.16 {ECO:0000269|PubMed:32474700};
GN   Name=Ppp6c {ECO:0000303|PubMed:26868000, ECO:0000312|MGI:MGI:1915107};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney, and Tongue;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=16769727; DOI=10.1074/jbc.m601772200;
RA   Stefansson B., Brautigan D.L.;
RT   "Protein phosphatase 6 subunit with conserved Sit4-associated protein
RT   domain targets IkappaBepsilon.";
RL   J. Biol. Chem. 281:22624-22634(2006).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and
RC   Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=26868000; DOI=10.1016/j.mod.2016.02.001;
RA   Ogoh H., Tanuma N., Matsui Y., Hayakawa N., Inagaki A., Sumiyoshi M.,
RA   Momoi Y., Kishimoto A., Suzuki M., Sasaki N., Ohuchi T., Nomura M.,
RA   Teruya Y., Yasuda K., Watanabe T., Shima H.;
RT   "The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for
RT   proper post-implantation embryogenesis.";
RL   Mech. Dev. 139:1-9(2016).
RN   [7]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=32474700; DOI=10.1007/s13238-020-00729-3;
RA   Li M., Shu H.B.;
RT   "Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity
RT   and innate antiviral response.";
RL   Protein Cell 11:584-599(2020).
CC   -!- FUNCTION: Catalytic subunit of protein phosphatase 6 (PP6)
CC       (PubMed:32474700). PP6 is a component of a signaling pathway regulating
CC       cell cycle progression in response to IL2 receptor stimulation (By
CC       similarity). N-terminal domain restricts G1 to S phase progression in
CC       cancer cells, in part through control of cyclin D13 During mitosis,
CC       regulates spindle positioning (By similarity). Down-regulates MAP3K7
CC       kinase activation of the IL1 signaling pathway by dephosphorylation of
CC       MAP3K7 (By similarity). Acts as a regulator of innate immunity by
CC       mediating dephosphorylation CGAS, STING1 and RIGI (PubMed:32474700).
CC       Participates also in the innate immune defense against viruses by
CC       desphosphorylating RIGI, an essential step that triggers RIGI-mediated
CC       signaling activation (By similarity). Also regulates innate immunity by
CC       acting as a negative regulator of the cGAS-STING pathway: mediates
CC       dephosphorylation and inactivation of CGAS and STING1
CC       (PubMed:32474700). CGAS dephosphorylation at 'Ser-420' impairs its
CC       ability to bind GTP, thereby inactivating it (PubMed:32474700).
CC       {ECO:0000250|UniProtKB:O00743, ECO:0000269|PubMed:32474700}.
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:0000269|PubMed:32474700};
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:O00743};
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: Protein phosphatase 6 (PP6) holoenzyme is proposed to be a
CC       heterotrimeric complex formed by the catalytic subunit, a SAPS domain-
CC       containing subunit (PP6R) and an ankyrin repeat-domain containing
CC       regulatory subunit (ARS). Interacts with subunits PPP6R1, PPP6R2 and
CC       PPP6R3. Interacts with subunit ANKRD28. Interacts with IGBP1. Interacts
CC       with MAP3K7. Interacts with NFKBIE. Interacts with TRIM14 and WRNIP1;
CC       these interactions positively regulate the RIG-I signaling pathway.
CC       {ECO:0000250|UniProtKB:O00743}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:O00743}.
CC       Cytoplasm {ECO:0000250|UniProtKB:O00743}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested with
CC       strongest expression in lung, spleen, liver, kidney and brain. Weaker
CC       expression observed in bladder, pancreas, heart and skeletal muscle.
CC       {ECO:0000269|PubMed:16769727}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality (PubMed:26868000). Embryos
CC       are apparently normal in blastocysts, but degenerate by E7.5 and
CC       display clear developmental defects at E8.5, suggesting that mutant
CC       embryos die after implantation (PubMed:26868000).
CC       {ECO:0000269|PubMed:26868000}.
CC   -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-6 (PP-V)
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AK002764; BAB22339.1; -; mRNA.
DR   EMBL; AK009104; BAB26073.1; -; mRNA.
DR   EMBL; AL928639; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC002223; AAH02223.1; -; mRNA.
DR   CCDS; CCDS16017.1; -.
DR   RefSeq; NP_077171.1; NM_024209.2.
DR   AlphaFoldDB; Q9CQR6; -.
DR   SMR; Q9CQR6; -.
DR   BioGRID; 212485; 50.
DR   IntAct; Q9CQR6; 38.
DR   MINT; Q9CQR6; -.
DR   STRING; 10090.ENSMUSP00000028087; -.
DR   GlyGen; Q9CQR6; 4 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; Q9CQR6; -.
DR   PhosphoSitePlus; Q9CQR6; -.
DR   SwissPalm; Q9CQR6; -.
DR   EPD; Q9CQR6; -.
DR   jPOST; Q9CQR6; -.
DR   MaxQB; Q9CQR6; -.
DR   PaxDb; 10090-ENSMUSP00000028087; -.
DR   PeptideAtlas; Q9CQR6; -.
DR   ProteomicsDB; 291720; -.
DR   Pumba; Q9CQR6; -.
DR   Antibodypedia; 30522; 327 antibodies from 32 providers.
DR   DNASU; 67857; -.
DR   Ensembl; ENSMUST00000028087.6; ENSMUSP00000028087.4; ENSMUSG00000026753.6.
DR   GeneID; 67857; -.
DR   KEGG; mmu:67857; -.
DR   UCSC; uc008joi.1; mouse.
DR   AGR; MGI:1915107; -.
DR   CTD; 5537; -.
DR   MGI; MGI:1915107; Ppp6c.
DR   VEuPathDB; HostDB:ENSMUSG00000026753; -.
DR   eggNOG; KOG0373; Eukaryota.
DR   GeneTree; ENSGT00550000074961; -.
DR   HOGENOM; CLU_004962_8_1_1; -.
DR   InParanoid; Q9CQR6; -.
DR   OMA; MEGFKYH; -.
DR   OrthoDB; 19833at2759; -.
DR   PhylomeDB; Q9CQR6; -.
DR   TreeFam; TF105563; -.
DR   Reactome; R-MMU-171319; Telomere Extension By Telomerase.
DR   Reactome; R-MMU-204005; COPII-mediated vesicle transport.
DR   BioGRID-ORCS; 67857; 25 hits in 85 CRISPR screens.
DR   ChiTaRS; Ppp6c; mouse.
DR   PRO; PR:Q9CQR6; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9CQR6; Protein.
DR   Bgee; ENSMUSG00000026753; Expressed in metanephric loop of Henle and 274 other cell types or tissues.
DR   ExpressionAtlas; Q9CQR6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:MGI.
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:SF10; SERINE_THREONINE-PROTEIN PHOSPHATASE 6 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.
DR   Genevisible; Q9CQR6; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cell cycle; Cytoplasm; Hydrolase; Immunity; Innate immunity;
KW   Manganese; Metal-binding; Mitochondrion; Protein phosphatase;
KW   Reference proteome.
FT   CHAIN           1..305
FT                   /note="Serine/threonine-protein phosphatase 6 catalytic
FT                   subunit"
FT                   /id="PRO_0000058878"
FT   ACT_SITE        114
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         53
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         55
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         81
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         81
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         113
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         163
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         237
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:O00743"
SQ   SEQUENCE   305 AA;  35159 MW;  662969DE1B2EF490 CRC64;
     MAPLDLDKYV EIARQCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV CGDIHGQFYD
     LCELFRTGGQ VPDTNYIFMG DFVDRGYYSL ETFTYLLALK AKWPDRITLL RGNHESRQIT
     QVYGFYDECQ TKYGNANAWR YCTKVFDMLT VAALIDEQIL CVHGGLSPDI KTLDQIRTIE
     RNQEIPHKGA FCDLVWSDPE DVDTWAISPR GAGWLFGAKV TNEFVHINNL KLICRAHQLV
     HEGYKFMFDE KLVTVWSAPN YCYRCGNIAS IMVFKDVNTR EPKLFRAVPD SERVIPPRTT
     TPYFL
//