PPP6_MOUSE
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 03-AUG-2022, entry version 148.
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 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 RIG-I/DDX58
CC (PubMed:32474700). Participates also in the innate immune defense
CC against viruses by desphosphorylating RIG-I/DDX58, an essential step
CC that triggers RIG-I/DDX58-mediated signaling activation (By
CC similarity). Also regulates innate immunity by acting as a negative
CC regulator of the cGAS-STING pathway: mediates dephosphorylation and
CC inactivation of CGAS and STING1 (PubMed:32474700). CGAS
CC dephosphorylation at 'Ser-420' impairs its ability to bind GTP, thereby
CC inactivating it (PubMed:32474700). {ECO:0000250|UniProtKB:O00743,
CC 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/DDX58 signaling
CC pathway. {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 iPTMnet; Q9CQR6; -.
DR PhosphoSitePlus; Q9CQR6; -.
DR SwissPalm; Q9CQR6; -.
DR EPD; Q9CQR6; -.
DR jPOST; Q9CQR6; -.
DR MaxQB; Q9CQR6; -.
DR PaxDb; Q9CQR6; -.
DR PeptideAtlas; Q9CQR6; -.
DR PRIDE; Q9CQR6; -.
DR ProteomicsDB; 291720; -.
DR Antibodypedia; 30522; 296 antibodies from 32 providers.
DR DNASU; 67857; -.
DR Ensembl; ENSMUST00000028087; ENSMUSP00000028087; ENSMUSG00000026753.
DR GeneID; 67857; -.
DR KEGG; mmu:67857; -.
DR UCSC; uc008joi.1; mouse.
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; CQNKYGN; -.
DR OrthoDB; 808922at2759; -.
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 80 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 271 other tissues.
DR ExpressionAtlas; Q9CQR6; baseline and differential.
DR Genevisible; Q9CQR6; MM.
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:0006470; P:protein dephosphorylation; ISO:MGI.
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 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
