PRDX6_HUMAN
ID PRDX6_HUMAN Reviewed; 224 AA.
AC P30041; A8JZY7; P32077; Q5TAH4; Q5ZEZ8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Peroxiredoxin-6;
DE EC=1.11.1.27 {ECO:0000269|PubMed:10893423, ECO:0000269|PubMed:9497358};
DE AltName: Full=1-Cys peroxiredoxin;
DE Short=1-Cys PRX;
DE AltName: Full=24 kDa protein;
DE AltName: Full=Acidic calcium-independent phospholipase A2;
DE Short=aiPLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:10893423, ECO:0000269|PubMed:26830860};
DE AltName: Full=Antioxidant protein 2;
DE AltName: Full=Glutathione-dependent peroxiredoxin {ECO:0000305};
DE AltName: Full=Liver 2D page spot 40;
DE AltName: Full=Lysophosphatidylcholine acyltransferase 5 {ECO:0000303|PubMed:26830860};
DE Short=LPC acyltransferase 5;
DE Short=LPCAT-5;
DE Short=Lyso-PC acyltransferase 5;
DE EC=2.3.1.23 {ECO:0000269|PubMed:26830860};
DE AltName: Full=Non-selenium glutathione peroxidase;
DE Short=NSGPx;
DE AltName: Full=Red blood cells page spot 12;
GN Name=PRDX6; Synonyms=AOP2, KIAA0106;
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].
RX PubMed=8999971; DOI=10.1074/jbc.272.4.2542;
RA Kim T.-S., Sundaresh C.S., Feinstein S.I., Dodia C., Skach W.R., Jain M.K.,
RA Nagase T., Seki N., Ishikawa K., Nomura N., Fisher A.B.;
RT "Identification of a human cDNA clone for lysosomal type Ca2+-independent
RT phospholipase A2 and properties of the expressed protein.";
RL J. Biol. Chem. 272:2542-2550(1997).
RN [2]
RP ERRATUM OF PUBMED:8999971.
RA Kim T.-S., Sundaresh C.S., Feinstein S.I., Dodia C., Skach W.R., Jain M.K.,
RA Nagase T., Seki N., Ishikawa K., Nomura N., Fisher A.B.;
RL J. Biol. Chem. 272:10981-10981(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9050990; DOI=10.1038/sj.onc.1200905;
RA Frank S., Munz B., Werner S.;
RT "The human homologue of a bovine non-selenium glutathione peroxidase is a
RT novel keratinocyte growth factor-regulated gene.";
RL Oncogene 14:915-921(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S.,
RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III. The
RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain, and Testis;
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 [10]
RP PROTEIN SEQUENCE OF 2-22.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [11]
RP PROTEIN SEQUENCE OF 2-22; 25-53; 85-106; 133-142; 145-155; 163-173 AND
RP 175-199, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 2-15.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [13]
RP PROTEIN SEQUENCE OF 2-13.
RC TISSUE=Erythrocyte;
RX PubMed=8313871; DOI=10.1002/elps.11501401183;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A., Pasquali C.,
RA Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C., Balant L.,
RA Hochstrasser D.F.;
RT "Plasma and red blood cell protein maps: update 1993.";
RL Electrophoresis 14:1223-1231(1993).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-99.
RA Dominguez O., Lombardia L.;
RT "DNA probes built and sequenced for microarrays hybridisations.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-47.
RX PubMed=9497358; DOI=10.1074/jbc.273.11.6303;
RA Kang S.W., Baines I.C., Rhee S.G.;
RT "Characterization of a mammalian peroxiredoxin that contains one conserved
RT cysteine.";
RL J. Biol. Chem. 273:6303-6311(1998).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-32 AND CYS-47.
RX PubMed=10893423; DOI=10.1074/jbc.m005073200;
RA Chen J.-W., Dodia C., Feinstein S.I., Jain M.K., Fisher A.B.;
RT "1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and
RT phospholipase A2 activities.";
RL J. Biol. Chem. 275:28421-28427(2000).
RN [17]
RP OVEROXIDATION AT CYS-47.
RX PubMed=12059788; DOI=10.1042/bj20020525;
RA Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A.,
RA Leize-Wagner E., Rabilloud T.;
RT "A method for detection of overoxidation of cysteines: peroxiredoxins are
RT oxidized in vivo at the active-site cysteine during oxidative stress.";
RL Biochem. J. 366:777-785(2002).
RN [18]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH STH.
RX PubMed=16186110; DOI=10.1074/jbc.m506116200;
RA Gao L., Tse S.-W., Conrad C., Andreadis A.;
RT "Saitohin, which is nested in the tau locus and confers allele-specific
RT susceptibility to several neurodegenerative diseases, interacts with
RT peroxiredoxin 6.";
RL J. Biol. Chem. 280:39268-39272(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-89, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP INTERACTION WITH APEX1, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19188445; DOI=10.1128/mcb.01337-08;
RA Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M.,
RA Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A.,
RA Quadrifoglio F., Tell G.;
RT "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the
RT rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-63 AND LYS-209, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
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 [25]
RP INTERACTION WITH FAM168B.
RX PubMed=20716133; DOI=10.1111/j.1582-4934.2010.01134.x;
RA Mishra M., Akatsu H., Heese K.;
RT "The novel protein MANI modulates neurogenesis and neurite-cone growth.";
RL J. Cell. Mol. Med. 15:1713-1725(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [27]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [28]
RP IDENTIFICATION BY MASS 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 [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
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 [31]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [32]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND PHOSPHORYLATION.
RX PubMed=26830860; DOI=10.1194/jlr.m064758;
RA Fisher A.B., Dodia C., Sorokina E.M., Li H., Zhou S., Raabe T.,
RA Feinstein S.I.;
RT "A novel lysophosphatidylcholine acyl transferase activity is expressed by
RT peroxiredoxin 6.";
RL J. Lipid Res. 57:587-596(2016).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), ACTIVE SITE, AND SUBUNIT.
RX PubMed=9587003; DOI=10.1038/nsb0598-400;
RA Choi H.-J., Kang S.W., Yang C.-H., Rhee S.G., Ryu S.-E.;
RT "Crystal structure of a novel human peroxidase enzyme at 2.0-A
RT resolution.";
RL Nat. Struct. Biol. 5:400-406(1998).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-224, AND SUBUNIT.
RX PubMed=27353378; DOI=10.1016/j.bbrc.2016.06.125;
RA Kim K.H., Lee W., Kim E.E.;
RT "Crystal structures of human peroxiredoxin 6 in different oxidation
RT states.";
RL Biochem. Biophys. Res. Commun. 477:717-722(2016).
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively (PubMed:9497358, PubMed:10893423). Can reduce H(2)O(2) and
CC short chain organic, fatty acid, and phospholipid hydroperoxides
CC (PubMed:10893423). Also has phospholipase activity, can therefore
CC either reduce the oxidized sn-2 fatty acyl group of phospholipids
CC (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids
CC (phospholipase activity) (PubMed:10893423, PubMed:26830860). These
CC activities are dependent on binding to phospholipids at acidic pH and
CC to oxidized phospholipds at cytosolic pH (PubMed:10893423). Plays a
CC role in cell protection against oxidative stress by detoxifying
CC peroxides and in phospholipid homeostasis (PubMed:10893423). Exhibits
CC acyl-CoA-dependent lysophospholipid acyltransferase which mediates the
CC conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-
CC phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-
CC 3-phosphocholine or PC) (PubMed:26830860). Shows a clear preference for
CC LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl
CC substrate (PubMed:26830860). {ECO:0000269|PubMed:10893423,
CC ECO:0000269|PubMed:26830860, ECO:0000269|PubMed:9497358}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hydroperoxide + 2 glutathione = an alcohol + glutathione
CC disulfide + H2O; Xref=Rhea:RHEA:62632, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58297; EC=1.11.1.27;
CC Evidence={ECO:0000269|PubMed:10893423, ECO:0000269|PubMed:9497358};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000269|PubMed:10893423, ECO:0000269|PubMed:26830860};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine + an acyl-CoA = a 1,2-
CC diacyl-sn-glycero-3-phosphocholine + CoA; Xref=Rhea:RHEA:12937,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57643, ChEBI:CHEBI:58168,
CC ChEBI:CHEBI:58342; EC=2.3.1.23;
CC Evidence={ECO:0000269|PubMed:26830860};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoyl-CoA
CC = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + CoA;
CC Xref=Rhea:RHEA:35983, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000269|PubMed:26830860};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35984;
CC Evidence={ECO:0000305|PubMed:26830860};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:41223, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000269|PubMed:26830860};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224;
CC Evidence={ECO:0000305|PubMed:26830860};
CC -!- ACTIVITY REGULATION: MJ33 or lithium;[(2R)-1-hexadecoxy-3-(2,2,2-
CC trifluoroethoxy)propan-2-yl] methyl phosphate inhibits its
CC phospholipase A2 activity (PubMed:26830860). CI-976 or 2,2-Dimethyl-N-
CC (2,4,6-trimethoxyphenyl)dodecanamide inhibits its
CC lysophosphatidylcholine acyltransferase activity (PubMed:26830860).
CC {ECO:0000269|PubMed:26830860}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for palmitoyl-CoA (lysophosphatidylcholine acyltransferase
CC activity at pH 4.0) {ECO:0000269|PubMed:26830860};
CC KM=15 uM for palmitoyl-CoA (lysophosphatidylcholine acyltransferase
CC activity for the phosphorylated form at pH 7.0)
CC {ECO:0000269|PubMed:26830860};
CC Vmax=30 nmol/min/mg enzyme with palmitoyl-CoA as substrate for
CC lysophosphatidylcholine acyltransferase activity (at pH 4.0)
CC {ECO:0000269|PubMed:26830860};
CC Vmax=770 nmol/min/mg enzyme with palmitoyl-CoA as substrate for
CC lysophosphatidylcholine acyltransferase activity (phosphorylated form
CC at pH 7.0) {ECO:0000269|PubMed:26830860};
CC pH dependence:
CC Shows a 3-fold greater lysophosphatidylcholine acyltransferase
CC activity at pH 4.0 than at pH 7.0. {ECO:0000269|PubMed:26830860};
CC -!- SUBUNIT: Homodimer (PubMed:9587003, PubMed:27353378). Interacts with
CC GSTP1; mediates PRDX6 glutathionylation and regeneration (By
CC similarity). Interacts with APEX1 (PubMed:19188445). Interacts with STH
CC (PubMed:16186110). May interact with FAM168B (PubMed:20716133). May
CC interact with HTR2A (By similarity). {ECO:0000250|UniProtKB:O08709,
CC ECO:0000250|UniProtKB:O77834, ECO:0000269|PubMed:16186110,
CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20716133,
CC ECO:0000269|PubMed:27353378, ECO:0000269|PubMed:9587003}.
CC -!- INTERACTION:
CC P30041; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-2255129, EBI-2875816;
CC P30041; Q7KZN9: COX15; NbExp=3; IntAct=EBI-2255129, EBI-3248549;
CC P30041; P09622: DLD; NbExp=3; IntAct=EBI-2255129, EBI-353366;
CC P30041; P12004: PCNA; NbExp=2; IntAct=EBI-2255129, EBI-358311;
CC P30041; P48556: PSMD8; NbExp=3; IntAct=EBI-2255129, EBI-359304;
CC P30041; P54274: TERF1; NbExp=2; IntAct=EBI-2255129, EBI-710997;
CC P30041; P21796: VDAC1; NbExp=3; IntAct=EBI-2255129, EBI-354158;
CC P30041; PRO_0000308465 [P29991]; Xeno; NbExp=3; IntAct=EBI-2255129, EBI-8826747;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16186110,
CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:9497358}. Lysosome
CC {ECO:0000250|UniProtKB:O35244}. Note=Also found in lung secretory
CC organelles (lamellar bodies). {ECO:0000250|UniProtKB:O35244}.
CC -!- PTM: Irreversibly inactivated by overoxidation of Cys-47 to sulfinic
CC acid (Cys-SO(2)H) and sulfonic acid (Cys-SO(3)H) forms upon oxidative
CC stress. {ECO:0000269|PubMed:12059788, ECO:0000269|PubMed:27353378}.
CC -!- PTM: Phosphorylation at Thr-177 by MAP kinases increases the
CC phospholipase activity of the enzyme (By similarity). The
CC phosphorylated form exhibits a greater lysophosphatidylcholine
CC acyltransferase activity compared to the non-phosphorylated form
CC (PubMed:26830860). {ECO:0000250|UniProtKB:O35244,
CC ECO:0000269|PubMed:26830860}.
CC -!- MISCELLANEOUS: The active site is a conserved redox-active cysteine
CC residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic
CC attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to
CC cysteine sulfenic acid (C(P)-SOH), which then reacts with another
CC cysteine residue, the resolving cysteine (C(R)), to form a disulfide
CC bridge. The disulfide is subsequently reduced by an appropriate
CC electron donor to complete the catalytic cycle. In this 1-Cys
CC peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide
CC with a cysteine from another protein or with a small thiol molecule.
CC C(P) is reactivated by glutathionylation mediated by glutathione S-
CC transferase Pi, followed by spontaneous reduction of the enzyme with
CC glutathione. {ECO:0000250|UniProtKB:O35244}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. Prx6 subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx6/";
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DR EMBL; D14662; BAA03496.1; -; mRNA.
DR EMBL; DQ230990; ABB02185.1; -; Genomic_DNA.
DR EMBL; AL139142; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK289352; BAF82041.1; -; mRNA.
DR EMBL; CH471067; EAW90944.1; -; Genomic_DNA.
DR EMBL; BC035857; AAH35857.1; -; mRNA.
DR EMBL; BC053550; AAH53550.1; -; mRNA.
DR EMBL; AJ844621; CAH59743.1; -; mRNA.
DR CCDS; CCDS1307.1; -.
DR RefSeq; NP_004896.1; NM_004905.2.
DR PDB; 1PRX; X-ray; 2.00 A; A/B=1-224.
DR PDB; 5B6M; X-ray; 2.50 A; A/B/C/D/E/F=1-224.
DR PDB; 5B6N; X-ray; 2.90 A; A/B/C/D/E/F=1-224.
DR PDBsum; 1PRX; -.
DR PDBsum; 5B6M; -.
DR PDBsum; 5B6N; -.
DR AlphaFoldDB; P30041; -.
DR BMRB; P30041; -.
DR SMR; P30041; -.
DR BioGRID; 114956; 192.
DR IntAct; P30041; 59.
DR MINT; P30041; -.
DR STRING; 9606.ENSP00000342026; -.
DR ChEMBL; CHEMBL4295741; -.
DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR DrugBank; DB09130; Copper.
DR SwissLipids; SLP:000001691; -.
DR MoonDB; P30041; Curated.
DR MoonProt; P30041; -.
DR PeroxiBase; 4426; Hs1CysPrx01.
DR CarbonylDB; P30041; -.
DR GlyGen; P30041; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30041; -.
DR MetOSite; P30041; -.
DR PhosphoSitePlus; P30041; -.
DR SwissPalm; P30041; -.
DR BioMuta; PRDX6; -.
DR DMDM; 1718024; -.
DR DOSAC-COBS-2DPAGE; P30041; -.
DR OGP; P30041; -.
DR REPRODUCTION-2DPAGE; IPI00220301; -.
DR REPRODUCTION-2DPAGE; P30041; -.
DR SWISS-2DPAGE; P30041; -.
DR CPTAC; CPTAC-117; -.
DR CPTAC; CPTAC-118; -.
DR EPD; P30041; -.
DR jPOST; P30041; -.
DR MassIVE; P30041; -.
DR PaxDb; P30041; -.
DR PeptideAtlas; P30041; -.
DR PRIDE; P30041; -.
DR ProteomicsDB; 54620; -.
DR TopDownProteomics; P30041; -.
DR Antibodypedia; 1681; 627 antibodies from 44 providers.
DR DNASU; 9588; -.
DR Ensembl; ENST00000340385.6; ENSP00000342026.5; ENSG00000117592.9.
DR GeneID; 9588; -.
DR KEGG; hsa:9588; -.
DR MANE-Select; ENST00000340385.6; ENSP00000342026.5; NM_004905.3; NP_004896.1.
DR CTD; 9588; -.
DR DisGeNET; 9588; -.
DR GeneCards; PRDX6; -.
DR HGNC; HGNC:16753; PRDX6.
DR HPA; ENSG00000117592; Low tissue specificity.
DR MIM; 602316; gene.
DR neXtProt; NX_P30041; -.
DR OpenTargets; ENSG00000117592; -.
DR PharmGKB; PA134992760; -.
DR VEuPathDB; HostDB:ENSG00000117592; -.
DR eggNOG; KOG0854; Eukaryota.
DR GeneTree; ENSGT00550000074794; -.
DR HOGENOM; CLU_042529_4_1_1; -.
DR InParanoid; P30041; -.
DR OMA; MIDYQDT; -.
DR OrthoDB; 1129256at2759; -.
DR PhylomeDB; P30041; -.
DR TreeFam; TF105183; -.
DR BioCyc; MetaCyc:HS04152-MON; -.
DR BRENDA; 1.11.1.27; 2681.
DR BRENDA; 2.3.1.23; 2681.
DR BRENDA; 3.1.1.4; 2681.
DR PathwayCommons; P30041; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P30041; -.
DR SIGNOR; P30041; -.
DR BioGRID-ORCS; 9588; 19 hits in 1077 CRISPR screens.
DR ChiTaRS; PRDX6; human.
DR EvolutionaryTrace; P30041; -.
DR GeneWiki; PRDX6; -.
DR GenomeRNAi; 9588; -.
DR Pharos; P30041; Tbio.
DR PRO; PR:P30041; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P30041; protein.
DR Bgee; ENSG00000117592; Expressed in corpus epididymis and 212 other tissues.
DR ExpressionAtlas; P30041; baseline and differential.
DR Genevisible; P30041; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0047184; F:1-acylglycerophosphocholine O-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0047499; F:calcium-independent phospholipase A2 activity; IMP:CAFA.
DR GO; GO:0004602; F:glutathione peroxidase activity; IMP:CAFA.
DR GO; GO:0042802; F:identical protein binding; IMP:CAFA.
DR GO; GO:0004623; F:phospholipase A2 activity; IDA:UniProtKB.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IEA:InterPro.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0098869; P:cellular oxidant detoxification; IMP:CAFA.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; IMP:CAFA.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; IGI:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:CAFA.
DR CDD; cd03016; PRX_1cys; 1.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR045020; PRX_1cys.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Antioxidant; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Lipid degradation; Lipid metabolism;
KW Lysosome; Multifunctional enzyme; Oxidoreductase; Peroxidase;
KW Phosphoprotein; Redox-active center; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:1286669, ECO:0000269|PubMed:8313871,
FT ECO:0000269|Ref.11, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..224
FT /note="Peroxiredoxin-6"
FT /id="PRO_0000135102"
FT DOMAIN 5..169
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 31..40
FT /note="Required and sufficient for targeting to lysosomes
FT and lamellar bodies"
FT /evidence="ECO:0000250|UniProtKB:O35244"
FT ACT_SITE 47
FT /note="Cysteine sulfenic acid (-SOH) intermediate; for
FT peroxidase activity"
FT /evidence="ECO:0000269|PubMed:10893423,
FT ECO:0000269|PubMed:9497358, ECO:0000269|PubMed:9587003"
FT ACT_SITE 140
FT /note="For phospholipase activity"
FT /evidence="ECO:0000250|UniProtKB:O35244"
FT SITE 32
FT /note="Important for phospholipase activity"
FT /evidence="ECO:0000305|PubMed:10893423"
FT MOD_RES 44
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 63
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 177
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:O35244"
FT MOD_RES 209
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 209
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08709"
FT MUTAGEN 32
FT /note="S->A: Loss of phospholipase activity, but no effect
FT on peroxidase activity."
FT /evidence="ECO:0000269|PubMed:9497358"
FT MUTAGEN 47
FT /note="C->S: Loss of peroxidase activity, but no effect on
FT phospholipase activity."
FT /evidence="ECO:0000269|PubMed:9497358"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:1PRX"
FT HELIX 25..29
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:1PRX"
FT HELIX 45..62
FT /evidence="ECO:0007829|PDB:1PRX"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 66..74
FT /evidence="ECO:0007829|PDB:1PRX"
FT HELIX 76..89
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:1PRX"
FT HELIX 109..113
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:5B6M"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:5B6M"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:5B6N"
FT HELIX 157..173
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1PRX"
FT HELIX 195..201
FT /evidence="ECO:0007829|PDB:1PRX"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1PRX"
SQ SEQUENCE 224 AA; 25035 MW; 017D955F0FEEDFBC CRC64;
MPGGLLLGDV APNFEANTTV GRIRFHDFLG DSWGILFSHP RDFTPVCTTE LGRAAKLAPE
FAKRNVKLIA LSIDSVEDHL AWSKDINAYN CEEPTEKLPF PIIDDRNREL AILLGMLDPA
EKDEKGMPVT ARVVFVFGPD KKLKLSILYP ATTGRNFDEI LRVVISLQLT AEKRVATPVD
WKDGDSVMVL PTIPEEEAKK LFPKGVFTKE LPSGKKYLRY TPQP
