PRDX6_BOVIN
ID PRDX6_BOVIN Reviewed; 224 AA.
AC O77834; Q5E9F3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Peroxiredoxin-6;
DE EC=1.11.1.27 {ECO:0000269|PubMed:10409692, ECO:0000269|PubMed:2373154};
DE AltName: Full=1-Cys peroxiredoxin;
DE Short=1-Cys PRX;
DE AltName: Full=Acidic calcium-independent phospholipase A2 {ECO:0000303|PubMed:9787801};
DE Short=aiPLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:9787801};
DE AltName: Full=Antioxidant protein 2;
DE AltName: Full=Ciliary body glutathione peroxidase;
DE AltName: Full=Glutathione-dependent peroxiredoxin {ECO:0000305};
DE AltName: Full=Lysophosphatidylcholine acyltransferase 5 {ECO:0000250|UniProtKB:P30041};
DE Short=LPC acyltransferase 5;
DE Short=LPCAT-5;
DE Short=Lyso-PC acyltransferase 5;
DE EC=2.3.1.23 {ECO:0000250|UniProtKB:P30041};
DE AltName: Full=Non-selenium glutathione peroxidase;
DE Short=NSGPx;
DE AltName: Full=PHGPx;
GN Name=PRDX6; Synonyms=AOP2, GPX, PHGPX;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ocular ciliary body;
RX PubMed=9748299; DOI=10.1074/jbc.273.40.26171;
RA Singh A.K., Shichi H.;
RT "A novel glutathione peroxidase in bovine eye. Sequence analysis, mRNA
RT level, and translation.";
RL J. Biol. Chem. 273:26171-26178(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Lung;
RX PubMed=10409692; DOI=10.1074/jbc.274.30.21326;
RA Fisher A.B., Dodia C., Manevich Y., Chen J.-W., Feinstein S.I.;
RT "Phospholipid hydroperoxides are substrates for non-selenium glutathione
RT peroxidase.";
RL J. Biol. Chem. 274:21326-21334(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Oviduct;
RA Rojas Garcia P.P., Einspanier R.;
RT "Glutathione peroxidase in the bovine oviduct.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 2-30, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2373154; DOI=10.1016/0014-4835(90)90040-2;
RA Shichi H., Demar J.C.;
RT "Non-selenium glutathione peroxidase without glutathione S-transferase
RT activity from bovine ciliary body.";
RL Exp. Eye Res. 50:513-520(1990).
RN [7]
RP PROTEIN SEQUENCE OF 2-16, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=9787801; DOI=10.1016/s0305-0491(98)10046-9;
RA Akiba S., Dodia C., Chen X., Fisher A.B.;
RT "Characterization of acidic Ca(2+)-independent phospholipase A2 of bovine
RT lung.";
RL Comp. Biochem. Physiol. 120:393-404(1998).
RN [8]
RP INTERACTION WITH GSTP1, AND ACTIVATION BY GLUTATHIONE.
RX PubMed=15004285; DOI=10.1073/pnas.0400181101;
RA Manevich Y., Feinstein S.I., Fisher A.B.;
RT "Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires
RT glutathionylation mediated by heterodimerization with pi GST.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:3780-3785(2004).
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively (PubMed:10409692, PubMed:2373154). Can reduce H(2)O(2) and
CC short chain organic, fatty acid, and phospholipid hydroperoxides
CC (PubMed:10409692). Also has phospholipase activity, and 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:10409692, PubMed:2373154,
CC PubMed:9787801). These activities are dependent on binding to
CC phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH
CC (By similarity). Plays a role in cell protection against oxidative
CC stress by detoxifying peroxides and in phospholipid homeostasis (By
CC similarity). Exhibits acyl-CoA-dependent lysophospholipid
CC acyltransferase which mediates the conversion of
CC lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC)
CC into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC)
CC (By similarity). Shows a clear preference for LPC as the
CC lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (By
CC similarity). {ECO:0000250|UniProtKB:P30041,
CC ECO:0000269|PubMed:10409692, ECO:0000269|PubMed:2373154,
CC ECO:0000269|PubMed:9787801}.
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:10409692, ECO:0000269|PubMed:2373154};
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:9787801};
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:0000250|UniProtKB:P30041};
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:0000250|UniProtKB:P30041};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35984;
CC Evidence={ECO:0000250|UniProtKB:P30041};
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:0000250|UniProtKB:P30041};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224;
CC Evidence={ECO:0000250|UniProtKB:P30041};
CC -!- COFACTOR:
CC Note=Does not need Ca(2+) as cofactor. {ECO:0000269|PubMed:9787801};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for H(2)O(2) {ECO:0000269|PubMed:2373154};
CC KM=180 uM for H(2)O(2) {ECO:0000269|PubMed:10409692};
CC KM=22 uM for tert-butyl hydroperoxide {ECO:0000269|PubMed:2373154};
CC KM=142 uM for tert-butyl hydroperoxide {ECO:0000269|PubMed:10409692};
CC KM=170 uM for cumene hydroperoxide {ECO:0000269|PubMed:2373154};
CC KM=120 uM for cumene hydroperoxide {ECO:0000269|PubMed:10409692};
CC KM=12 uM for triphenylcarbinyl hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC KM=34 uM for linoleic hydroperoxide {ECO:0000269|PubMed:2373154};
CC KM=141 uM for linolenoyl hydroperoxide {ECO:0000269|PubMed:10409692};
CC KM=135 uM for arachidonoyl hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC KM=120 uM for PLCP hydroperoxide {ECO:0000269|PubMed:10409692};
CC KM=129 uM for PACP hydroperoxide {ECO:0000269|PubMed:10409692};
CC KM=22 uM for 5-phenyl-3-pentenyl hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC KM=350 uM for dipalmitoyl phosphatidylcholine (at pH 4)
CC {ECO:0000269|PubMed:9787801};
CC Vmax=5.07 umol/min/mg enzyme for H(2)O(2)
CC {ECO:0000269|PubMed:2373154};
CC Vmax=1810 nmol/min/mg enzyme for H(2)O(2)
CC {ECO:0000269|PubMed:10409692};
CC Vmax=8.56 umol/min/mg enzyme for tert-butyl hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC Vmax=1270 nmol/min/mg enzyme for tert-butyl hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=9.18 umol/min/mg enzyme for cumene hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC Vmax=1120 nmol/min/mg enzyme for cumene hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=2.57 umol/min/mg enzyme for triphenylcarbinyl hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC Vmax=9.88 umol/min/mg enzyme for linoleic hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC Vmax=1390 nmol/min/mg enzyme for linolenoyl hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=7.34 umol/min/mg enzyme for 5-phenyl-3-pentenyl hydroperoxide
CC {ECO:0000269|PubMed:2373154};
CC Vmax=1380 nmol/min/mg enzyme for arachidonoyl hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=1500 nmol/min/mg enzyme for PLCP hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=1640 nmol/min/mg enzyme for PACP hydroperoxide
CC {ECO:0000269|PubMed:10409692};
CC Vmax=4225 nmol/h/mg enzyme for dipalmitoyl phosphatidylcholine (at pH
CC 4) {ECO:0000269|PubMed:9787801};
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:10409692};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with GSTP1; mediates
CC PRDX6 glutathionylation and regeneration (PubMed:15004285). Interacts
CC with APEX1. Interacts with STH. May interact with FAM168B (By
CC similarity). May interact with HTR2A (By similarity).
CC {ECO:0000250|UniProtKB:O08709, ECO:0000250|UniProtKB:P30041,
CC ECO:0000269|PubMed:15004285}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9787801}. Lysosome
CC {ECO:0000269|PubMed:9787801}. Note=Also found in lung secretory
CC organelles (lamellar bodies). {ECO:0000269|PubMed:9787801}.
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:0000250|UniProtKB:P30041}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:O35244}.
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:0000305|PubMed:15004285}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. Prx6 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF080228; AAC63016.1; -; mRNA.
DR EMBL; AF090194; AAC84043.1; -; mRNA.
DR EMBL; AJ243848; CAB64802.1; -; mRNA.
DR EMBL; BT020967; AAX08984.1; -; mRNA.
DR EMBL; BC102172; AAI02173.1; -; mRNA.
DR RefSeq; NP_777068.1; NM_174643.1.
DR AlphaFoldDB; O77834; -.
DR SMR; O77834; -.
DR STRING; 9913.ENSBTAP00000006383; -.
DR PeroxiBase; 4423; Bt1CysPrx.
DR PaxDb; O77834; -.
DR PeptideAtlas; O77834; -.
DR PRIDE; O77834; -.
DR Ensembl; ENSBTAT00000006383; ENSBTAP00000006383; ENSBTAG00000004855.
DR GeneID; 282438; -.
DR KEGG; bta:282438; -.
DR CTD; 9588; -.
DR VEuPathDB; HostDB:ENSBTAG00000004855; -.
DR VGNC; VGNC:33304; PRDX6.
DR eggNOG; KOG0854; Eukaryota.
DR GeneTree; ENSGT00550000074794; -.
DR HOGENOM; CLU_042529_4_1_1; -.
DR InParanoid; O77834; -.
DR OMA; MIDYQDT; -.
DR OrthoDB; 1129256at2759; -.
DR TreeFam; TF105183; -.
DR BRENDA; 1.11.1.27; 908.
DR BRENDA; 3.1.1.4; 908.
DR Reactome; R-BTA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000004855; Expressed in rumen papilla and 104 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:AgBase.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0047184; F:1-acylglycerophosphocholine O-acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0004601; F:peroxidase activity; ISS:AgBase.
DR GO; GO:0004623; F:phospholipase A2 activity; ISS:UniProtKB.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:AgBase.
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 Acetylation; Antioxidant; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lysosome; Multifunctional enzyme;
KW Oxidoreductase; Peroxidase; Phosphoprotein; Redox-active center;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P30041"
FT CHAIN 2..224
FT /note="Peroxiredoxin-6"
FT /id="PRO_0000135101"
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:0000250|UniProtKB:P30041"
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:0000250|UniProtKB:O35244"
FT MOD_RES 44
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30041"
FT MOD_RES 63
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30041"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P30041"
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:0000250|UniProtKB:P30041"
FT MOD_RES 209
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08709"
SQ SEQUENCE 224 AA; 25067 MW; 4013D59C4D9FC05E CRC64;
MPGGLLLGDE APNFEANTTI GRIRFHDYLG DSWGILFSHP RDFTPVCTTE LGRAAKLAPE
FAKRNVKMIA LSIDSVEDHL AWSKDINAYN GEEPTEKLPF PIIDDKNRDL AIQLGMLDPA
EKDEKGMPVT ARVVFIFGPD KKLKLSILYP ATTGRNFDEI LRVIISLQLT AEKRVATPVD
WKNGDSVMVL PTIPEEEAKK LFPKGVFTKE LPSGKKYLRY TPQP
