PPP6_HUMAN
ID PPP6_HUMAN Reviewed; 305 AA.
AC O00743; B2R5V6; B7Z2W9; B7Z5K9; Q5U0A2; Q9UIC9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit {ECO:0000305};
DE Short=PP6C {ECO:0000303|PubMed:29053956};
DE EC=3.1.3.16 {ECO:0000269|PubMed:17079228, ECO:0000269|PubMed:29053956, ECO:0000269|PubMed:32474700};
DE Contains:
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed;
GN Name=PPP6C {ECO:0000303|PubMed:29053956, ECO:0000312|HGNC:HGNC:9323};
GN Synonyms=PPP6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9013334; DOI=10.1242/jcs.109.12.2865;
RA Bastians H., Ponstingl H.;
RT "The novel human protein serine/threonine phosphatase 6 is a functional
RT homologue of budding yeast Sit4p and fission yeast ppe1, which are involved
RT in cell cycle regulation.";
RL J. Cell Sci. 109:2865-2874(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=10227379;
RX DOI=10.1002/(sici)1097-4644(19990501)73:2<153::aid-jcb2>3.0.co;2-7;
RA Filali M., Li S., Kim H.W., Wadzinski B., Kamoun M.;
RT "Identification of a type 6 protein Ser/Thr phosphatase regulated by
RT interleukin-2 stimulation.";
RL J. Cell. Biochem. 73:153-163(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [8]
RP PROTEIN SEQUENCE OF 2-14; 67-100; 118-140; 145-171; 211-231 AND 252-275,
RP CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP INTERACTION WITH IGBP1.
RX PubMed=9647778; DOI=10.1006/bbrc.1998.8792;
RA Chen J., Peterson R.T., Schreiber S.L.;
RT "Alpha 4 associates with protein phosphatases 2A, 4, and 6.";
RL Biochem. Biophys. Res. Commun. 247:827-832(1998).
RN [10]
RP INTERACTION WITH NFKBIE; PPP6R1 AND PPP6R2, SUBCELLULAR LOCATION, AND
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH MAP3K7.
RX PubMed=17079228; DOI=10.1074/jbc.m608155200;
RA Kajino T., Ren H., Iemura S., Natsume T., Stefansson B., Brautigan D.L.,
RA Matsumoto K., Ninomiya-Tsuji J.;
RT "Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1
RT signaling pathway.";
RL J. Biol. Chem. 281:39891-39896(2006).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17568194; DOI=10.4161/cc.6.11.4276;
RA Stefansson B., Brautigan D.L.;
RT "Protein phosphatase PP6 N terminal domain restricts G1 to S phase
RT progression in human cancer cells.";
RL Cell Cycle 6:1386-1392(2007).
RN [13]
RP INTERACTION WITH ANKRD28; PPP6R1; PPP6R2 AND PPP6R3.
RX PubMed=18186651; DOI=10.1021/bi7022877;
RA Stefansson B., Ohama T., Daugherty A.E., Brautigan D.L.;
RT "Protein phosphatase 6 regulatory subunits composed of ankyrin repeat
RT domains.";
RL Biochemistry 47:1442-1451(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP FUNCTION.
RX PubMed=27335426; DOI=10.1242/jcs.184416;
RA Kotak S., Afshar K., Busso C., Goenczy P.;
RT "Aurora A kinase regulates proper spindle positioning in C. elegans and in
RT human cells.";
RL J. Cell Sci. 129:3015-3025(2016).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TRIM14 AND WRNIP1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29053956; DOI=10.1016/j.molcel.2017.09.035;
RA Tan P., He L., Cui J., Qian C., Cao X., Lin M., Zhu Q., Li Y., Xing C.,
RA Yu X., Wang H.Y., Wang R.F.;
RT "Assembly of the WHIP-TRIM14-PPP6C mitochondrial complex promotes RIG-I-
RT mediated antiviral signaling.";
RL Mol. Cell 68:293-307(2017).
RN [19]
RP FUNCTION, VARIANTS TYR-55; TYR-114 AND ARG-189, AND CHARACTERIZATION OF
RP VARIANTS TYR-55; TYR-114 AND ARG-189.
RX PubMed=32753499; DOI=10.1128/mbio.01728-20;
RA Ni G., Ma Z., Wong J.P., Zhang Z., Cousins E., Major M.B., Damania B.;
RT "PPP6C negatively regulates STING-dependent innate immune responses.";
RL MBio 11:0-0(2020).
RN [20]
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:17079228, PubMed:29053956, PubMed:32474700). PP6 is a component
CC of a signaling pathway regulating cell cycle progression in response to
CC IL2 receptor stimulation (PubMed:10227379). N-terminal domain restricts
CC G1 to S phase progression in cancer cells, in part through control of
CC cyclin D1 (PubMed:17568194). During mitosis, regulates spindle
CC positioning (PubMed:27335426). Down-regulates MAP3K7 kinase activation
CC of the IL1 signaling pathway by dephosphorylation of MAP3K7
CC (PubMed:17079228). 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
CC (PubMed:29053956). Also regulates innate immunity by acting as a
CC negative regulator of the cGAS-STING pathway: mediates
CC dephosphorylation and inactivation of CGAS and STING1 (PubMed:32753499,
CC PubMed:32474700). CGAS dephosphorylation at 'Ser-435' impairs its
CC ability to bind GTP, thereby inactivating it (PubMed:32474700).
CC {ECO:0000269|PubMed:10227379, ECO:0000269|PubMed:17079228,
CC ECO:0000269|PubMed:17568194, ECO:0000269|PubMed:27335426,
CC ECO:0000269|PubMed:29053956, ECO:0000269|PubMed:32474700,
CC ECO:0000269|PubMed:32753499}.
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:29053956, 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:0000269|PubMed:17079228, ECO:0000269|PubMed:29053956};
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) (PubMed:18186651). Interacts with subunits
CC PPP6R1, PPP6R2 and PPP6R3 (PubMed:16769727, PubMed:18186651). Interacts
CC with subunit ANKRD28 (PubMed:18186651). Interacts with IGBP1
CC (PubMed:9647778). Interacts with MAP3K7 (PubMed:17079228). Interacts
CC with NFKBIE (PubMed:16769727). Interacts with TRIM14 and WRNIP1; these
CC interactions positively regulate the RIG-I/DDX58 signaling pathway
CC (PubMed:29053956). {ECO:0000269|PubMed:16769727,
CC ECO:0000269|PubMed:17079228, ECO:0000269|PubMed:18186651,
CC ECO:0000269|PubMed:29053956, ECO:0000269|PubMed:9647778}.
CC -!- INTERACTION:
CC O00743; O15084: ANKRD28; NbExp=10; IntAct=EBI-359751, EBI-359567;
CC O00743; P78318: IGBP1; NbExp=17; IntAct=EBI-359751, EBI-1055954;
CC O00743; O43318: MAP3K7; NbExp=4; IntAct=EBI-359751, EBI-358684;
CC O00743; Q9UPN7: PPP6R1; NbExp=12; IntAct=EBI-359751, EBI-359745;
CC O00743; O75170: PPP6R2; NbExp=9; IntAct=EBI-359751, EBI-359739;
CC O00743; Q5H9R7: PPP6R3; NbExp=6; IntAct=EBI-359751, EBI-355498;
CC O00743; O75663: TIPRL; NbExp=4; IntAct=EBI-359751, EBI-1054735;
CC O00743; Q08AM6: VAC14; NbExp=3; IntAct=EBI-359751, EBI-2107455;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:29053956}.
CC Cytoplasm {ECO:0000269|PubMed:16769727, ECO:0000269|PubMed:17568194}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00743-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00743-2; Sequence=VSP_038376;
CC Name=3;
CC IsoId=O00743-3; Sequence=VSP_041158;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested with
CC highest expression levels in testis, heart, kidney, brain, stomach,
CC liver and skeletal muscle and lowest in placenta, lung colon and
CC spleen. {ECO:0000269|PubMed:16769727, ECO:0000269|PubMed:9013334}.
CC -!- INDUCTION: Regulated by IL2/interleukin-2 in peripheral blood T cells.
CC {ECO:0000269|PubMed:10227379}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-6 (PP-V)
CC subfamily. {ECO:0000305}.
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DR EMBL; X92972; CAA63549.1; -; mRNA.
DR EMBL; AF035158; AAD45400.2; -; mRNA.
DR EMBL; AK295190; BAH12005.1; -; mRNA.
DR EMBL; AK299087; BAH12945.1; -; mRNA.
DR EMBL; AK312332; BAG35253.1; -; mRNA.
DR EMBL; BT019708; AAV38514.1; -; mRNA.
DR EMBL; AL445930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87611.1; -; Genomic_DNA.
DR EMBL; BC006990; AAH06990.1; -; mRNA.
DR CCDS; CCDS48018.1; -. [O00743-3]
DR CCDS; CCDS48019.1; -. [O00743-2]
DR CCDS; CCDS6861.1; -. [O00743-1]
DR RefSeq; NP_001116827.1; NM_001123355.1. [O00743-3]
DR RefSeq; NP_001116841.1; NM_001123369.1. [O00743-2]
DR RefSeq; NP_002712.1; NM_002721.4. [O00743-1]
DR AlphaFoldDB; O00743; -.
DR SMR; O00743; -.
DR BioGRID; 111529; 189.
DR CORUM; O00743; -.
DR DIP; DIP-27581N; -.
DR IntAct; O00743; 77.
DR MINT; O00743; -.
DR ChEMBL; CHEMBL4105731; -.
DR DEPOD; PPP6C; -.
DR iPTMnet; O00743; -.
DR PhosphoSitePlus; O00743; -.
DR BioMuta; PPP6C; -.
DR OGP; O00743; -.
DR EPD; O00743; -.
DR jPOST; O00743; -.
DR MassIVE; O00743; -.
DR MaxQB; O00743; -.
DR PeptideAtlas; O00743; -.
DR PRIDE; O00743; -.
DR ProteomicsDB; 48009; -. [O00743-1]
DR ProteomicsDB; 48010; -. [O00743-2]
DR ProteomicsDB; 48011; -. [O00743-3]
DR Antibodypedia; 30522; 296 antibodies from 32 providers.
DR DNASU; 5537; -.
DR Ensembl; ENST00000373547.9; ENSP00000362648.4; ENSG00000119414.12. [O00743-1]
DR Ensembl; ENST00000415905.5; ENSP00000411744.1; ENSG00000119414.12. [O00743-2]
DR Ensembl; ENST00000451402.5; ENSP00000392147.1; ENSG00000119414.12. [O00743-3]
DR GeneID; 5537; -.
DR KEGG; hsa:5537; -.
DR MANE-Select; ENST00000373547.9; ENSP00000362648.4; NM_002721.5; NP_002712.1.
DR UCSC; uc004bpg.5; human. [O00743-1]
DR CTD; 5537; -.
DR DisGeNET; 5537; -.
DR GeneCards; PPP6C; -.
DR HGNC; HGNC:9323; PPP6C.
DR HPA; ENSG00000119414; Low tissue specificity.
DR MIM; 612725; gene.
DR neXtProt; NX_O00743; -.
DR OpenTargets; ENSG00000119414; -.
DR PharmGKB; PA33687; -.
DR VEuPathDB; HostDB:ENSG00000119414; -.
DR GeneTree; ENSGT00550000074961; -.
DR HOGENOM; CLU_004962_8_1_1; -.
DR InParanoid; O00743; -.
DR OMA; CQNKYGN; -.
DR OrthoDB; 808922at2759; -.
DR PhylomeDB; O00743; -.
DR TreeFam; TF105563; -.
DR PathwayCommons; O00743; -.
DR Reactome; R-HSA-171319; Telomere Extension By Telomerase.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR SignaLink; O00743; -.
DR SIGNOR; O00743; -.
DR BioGRID-ORCS; 5537; 432 hits in 1093 CRISPR screens.
DR ChiTaRS; PPP6C; human.
DR GeneWiki; PPP6C; -.
DR GenomeRNAi; 5537; -.
DR Pharos; O00743; Tbio.
DR PRO; PR:O00743; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O00743; protein.
DR Bgee; ENSG00000119414; Expressed in oocyte and 210 other tissues.
DR ExpressionAtlas; O00743; baseline and differential.
DR Genevisible; O00743; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0048208; P:COPII vesicle coating; TAS:Reactome.
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; IDA: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; Alternative splicing; Cell cycle; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Immunity; Innate immunity; Manganese;
KW Metal-binding; Mitochondrion; Protein phosphatase; Reference proteome.
FT CHAIN 1..305
FT /note="Serine/threonine-protein phosphatase 6 catalytic
FT subunit"
FT /id="PRO_0000424504"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..305
FT /note="Serine/threonine-protein phosphatase 6 catalytic
FT subunit, N-terminally processed"
FT /id="PRO_0000058877"
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:0007744|PubMed:22814378"
FT VAR_SEQ 25
FT /note="K -> KVSPICGLAPSGCGAPAGRPFLSPGPPPVFHFLRFLKE (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041158"
FT VAR_SEQ 58..79
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038376"
FT VARIANT 55
FT /note="H -> Y (found in patients with melanomas; decreased
FT protein phosphatase activity, leading to increased
FT phosphorylation of STING1)"
FT /evidence="ECO:0000269|PubMed:32753499"
FT /id="VAR_085528"
FT VARIANT 114
FT /note="H -> Y (found in patients with melanomas; decreased
FT protein phosphatase activity, leading to increased
FT phosphorylation of STING1)"
FT /evidence="ECO:0000269|PubMed:32753499"
FT /id="VAR_085529"
FT VARIANT 189
FT /note="G -> R (found in patients with melanomas; decreased
FT protein phosphatase activity, leading to increased
FT phosphorylation of STING1)"
FT /evidence="ECO:0000269|PubMed:32753499"
FT /id="VAR_085530"
FT CONFLICT 61..64
FT /note="LCEL -> AG (in Ref. 2; AAD45400)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 35144 MW; 55E95DB6CEA7CFF4 CRC64;
MAPLDLDKYV EIARLCKYLP 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
