PRDX6_PONAB
ID PRDX6_PONAB Reviewed; 224 AA.
AC Q5R7E0;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Peroxiredoxin-6;
DE EC=1.11.1.27 {ECO:0000250|UniProtKB:P30041};
DE AltName: Full=1-Cys peroxiredoxin;
DE Short=1-Cys PRX;
DE AltName: Full=Acidic calcium-independent phospholipase A2;
DE Short=aiPLA2;
DE EC=3.1.1.4;
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;
GN Name=PRDX6;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively (By similarity). Can reduce H(2)O(2) and short chain
CC organic, fatty acid, and phospholipid hydroperoxides (By similarity).
CC Also has phospholipase activity, and can therefore either reduce the
CC oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity)
CC or hydrolyze the sn-2 ester bond of phospholipids (phospholipase
CC activity) (By similarity). 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 -!- 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:0000250|UniProtKB:P30041};
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:0000250|UniProtKB:P30041};
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 -!- SUBUNIT: Homodimer (By similarity). Interacts with GSTP1; mediates
CC PRDX6 glutathionylation and regeneration (By similarity). 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:O77834,
CC ECO:0000250|UniProtKB:P30041}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O35244}.
CC Lysosome {ECO:0000250|UniProtKB:O35244}. Note=Also found in lung
CC secretory 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: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:0000250|UniProtKB:O35244}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. Prx6 subfamily.
CC {ECO:0000305}.
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DR EMBL; CR860178; CAH92320.1; -; mRNA.
DR RefSeq; NP_001126361.1; NM_001132889.1.
DR AlphaFoldDB; Q5R7E0; -.
DR BMRB; Q5R7E0; -.
DR SMR; Q5R7E0; -.
DR STRING; 9601.ENSPPYP00000000577; -.
DR PeroxiBase; 4422; Ppy1CysPrx.
DR GeneID; 100173342; -.
DR KEGG; pon:100173342; -.
DR CTD; 9588; -.
DR eggNOG; KOG0854; Eukaryota.
DR InParanoid; Q5R7E0; -.
DR OrthoDB; 1129256at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0047184; F:1-acylglycerophosphocholine O-acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0004623; F:phospholipase A2 activity; ISS:UniProtKB.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Acetylation; Antioxidant; Cytoplasm; Hydrolase; Lipid degradation;
KW Lipid metabolism; Lysosome; Multifunctional enzyme; Oxidoreductase;
KW Peroxidase; Phosphoprotein; Redox-active center; Reference proteome;
KW Transferase.
FT CHAIN 1..224
FT /note="Peroxiredoxin-6"
FT /id="PRO_0000256862"
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; 25021 MW; 00C9B2EEA4EF6FAC CRC64;
MPGGLLLGDV APNFEANTTV GRIRFHDFLG DSWGILFSHP RDFTPVCTTE LGRAAKLAPE
FAKRNVKLIA LSIDSVEDHL AWSKDINAYN CEEPTEKLPF PIIDDRNREL AILLGMLDPA
EKDEKGMPGT ARVVFVFGPD KKLKLSILYP ATTGRNFDEI LRVVISLQLT AEKRVATPVD
WKDGDSVMVL PTIPEEEAKK LFPKGVFTKE LPSGRKYLRY TPQP
