ID   PPOC_ASPFU              Reviewed;        1121 AA.
AC   Q4WY82; A7YMT7;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 2.
DT   24-JAN-2024, entry version 130.
DE   RecName: Full=Linoleate 10R-lipoxygenase;
DE            EC=1.13.11.62;
DE   AltName: Full=Cyclooxygenase-like fatty acid oxygenase {ECO:0000312|EMBL:ABV21633.1};
DE   AltName: Full=Fatty acid oxygenase ppoC {ECO:0000312|EMBL:EAL92371.2};
DE   AltName: Full=Linoleate 10R-dioxygenase {ECO:0000303|PubMed:19289462, ECO:0000312|EMBL:ACL14177.1};
DE            Short=10R-DOX {ECO:0000303|PubMed:19289462};
DE   AltName: Full=Psi-producing oxygenase C {ECO:0000303|PubMed:16040966};
DE            Short=AfPpoC {ECO:0000303|PubMed:16040966};
GN   Name=ppoC {ECO:0000312|EMBL:ABV21633.1}; ORFNames=AFUA_3G12120;
OS   Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 /
OS   Af293) (Neosartorya fumigata).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=330879;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:ACL14177.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF LEU-306; LEU-384 AND
RP   VAL-388.
RX   PubMed=19289462; DOI=10.1074/jbc.m808665200;
RA   Garscha U., Oliw E.H.;
RT   "Leucine/valine residues direct oxygenation of linoleic acid by (10R)- and
RT   (8R)-dioxygenases: expression and site-directed mutagenesis of (10R)-
RT   dioxygenase with epoxyalcohol synthase activity.";
RL   J. Biol. Chem. 284:13755-13765(2009).
RN   [2] {ECO:0000312|EMBL:EAL92371.2}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293;
RX   PubMed=16372009; DOI=10.1038/nature04332;
RA   Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA   Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA   Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA   Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA   Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA   Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA   Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA   Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA   Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA   Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA   O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA   Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA   Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA   Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA   Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA   Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA   Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA   Barrell B.G., Denning D.W.;
RT   "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT   Aspergillus fumigatus.";
RL   Nature 438:1151-1156(2005).
RN   [3] {ECO:0000305, ECO:0000312|EMBL:ABV21633.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 237-1121, FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293;
RX   PubMed=16040966; DOI=10.1128/iai.73.8.4548-4559.2005;
RA   Tsitsigiannis D.I., Bok J.W., Andes D., Nielsen K.F., Frisvad J.C.,
RA   Keller N.P.;
RT   "Aspergillus cyclooxygenase-like enzymes are associated with prostaglandin
RT   production and virulence.";
RL   Infect. Immun. 73:4548-4559(2005).
CC   -!- FUNCTION: Responsible for the synthesis of various fatty acid-derived
CC       oxylipins. Oxidizes linoleic acid primarily to 10R-hydroperoxy-8,12-
CC       octadecadienoic acid (10R-HPODE) and, to a lesser extent, 8R-
CC       hydroperoxylinoleic acid (8R-HPODE). Also synthesizes 10-hydroxy-
CC       octadeca-8,12-dienoic acid (10-HODE) from linoleic acid and primarily
CC       8R-hydroxy-octadeca-9-monoenoic acid (8-HOME, also known as psiB beta)
CC       from oleic acid. 8-HOME forms part of psi factor, a mixture of
CC       oxylipins that regulates the balance between sexual and asexual spore
CC       production. Displays epoxyalcohol synthase activity. Plays a role in
CC       the synthesis of prostaglandins which may be required for
CC       pathogenicity. {ECO:0000269|PubMed:16040966,
CC       ECO:0000269|PubMed:19289462}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + O2 = (8E,10R,12Z)-10-
CC         hydroperoxyoctadeca-8,12-dienoate; Xref=Rhea:RHEA:31695,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:30245, ChEBI:CHEBI:63324;
CC         EC=1.13.11.62; Evidence={ECO:0000269|PubMed:19289462};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.05 mM for linoleic acid {ECO:0000269|PubMed:19289462};
CC   -!- DISRUPTION PHENOTYPE: Decreased prostaglandin (PG) production in triple
CC       ppoA/ppoB/ppoC mutants. The triple mutant is hypervirulent in the
CC       invasive pulmonary aspergillosis murine model system and shows
CC       increased tolerance to hydrogen peroxide stress.
CC       {ECO:0000269|PubMed:16040966}.
CC   -!- SIMILARITY: Belongs to the peroxidase family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00298}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; FJ538183; ACL14177.1; -; mRNA.
DR   EMBL; AAHF01000002; EAL92371.2; -; Genomic_DNA.
DR   EMBL; EU020168; ABV21633.1; -; mRNA.
DR   RefSeq; XP_754409.2; XM_749316.2.
DR   AlphaFoldDB; Q4WY82; -.
DR   SMR; Q4WY82; -.
DR   STRING; 330879.Q4WY82; -.
DR   PeroxiBase; 5291; AfumLDS03.
DR   EnsemblFungi; EAL92371; EAL92371; AFUA_3G12120.
DR   GeneID; 3512584; -.
DR   KEGG; afm:AFUA_3G12120; -.
DR   VEuPathDB; FungiDB:Afu3g12120; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   HOGENOM; CLU_002329_1_0_1; -.
DR   InParanoid; Q4WY82; -.
DR   OMA; RHYTIDY; -.
DR   OrthoDB; 3322316at2759; -.
DR   BioCyc; MetaCyc:MONOMER-16944; -.
DR   BRENDA; 1.13.11.62; 508.
DR   SABIO-RK; Q4WY82; -.
DR   PHI-base; PHI:496; -.
DR   Proteomes; UP000002530; Chromosome 3.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:InterPro.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:AspGD.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   CDD; cd20612; CYP_LDS-like_C; 1.
DR   CDD; cd09817; linoleate_diol_synthase_like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR010255; Haem_peroxidase_sf.
DR   InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR   InterPro; IPR034812; Ppo-like_N.
DR   PANTHER; PTHR11903:SF13; LINOLEATE 10R-LIPOXYGENASE; 1.
DR   PANTHER; PTHR11903; PROSTAGLANDIN G/H SYNTHASE; 1.
DR   Pfam; PF03098; An_peroxidase; 2.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   SUPFAM; SSF48113; Heme-dependent peroxidases; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
PE   1: Evidence at protein level;
KW   Calcium; Dioxygenase; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Hydrogen peroxide; Iron; Lipid biosynthesis; Lipid metabolism;
KW   Metal-binding; Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW   Prostaglandin metabolism; Reference proteome.
FT   CHAIN           1..1121
FT                   /note="Linoleate 10R-lipoxygenase"
FT                   /id="PRO_0000397942"
FT   REGION          1..66
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        19..40
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        41..63
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        253
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   BINDING         254
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   BINDING         269
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   BINDING         271
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   BINDING         273
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   BINDING         275
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   SITE            305
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   MUTAGEN         306
FT                   /note="L->A,V: Slightly lower synthesis of 8R-HODE. Little
FT                   effect on epoxyalcohol synthase activity."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         384
FT                   /note="L->A: Increased synthesis of 8-HPODE, 8-HODE and
FT                   altered product stereochemistry."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         384
FT                   /note="L->F: Increased synthesis of 8-HODE, synthesis of
FT                   9-HPODE and 13-HPODE. Retains chirality in 10- and 8-HODE."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         384
FT                   /note="L->M: Significantly increased synthesis of 8-HODE."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         384
FT                   /note="L->V: Increased synthesis of 8-HPODE and 8-HODE."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         388
FT                   /note="V->F: Increased synthesis of 8-HODE, synthesis of
FT                   9-HPODE and 13-HPODE. Retains chirality in 10- and 8-HODE."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   MUTAGEN         388
FT                   /note="V->L: Increased synthesis of 8-HODE."
FT                   /evidence="ECO:0000269|PubMed:19289462"
FT   CONFLICT        237..253
FT                   /note="PNKVSSVFFYWASLIIH -> MILKTSTRSVKDFNAKT (in Ref. 3;
FT                   ABV21633)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        323..331
FT                   /note="FHNYAVEQL -> SISNTN (in Ref. 3; ABV21633)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        369
FT                   /note="L -> LLTNDS (in Ref. 3; ABV21633)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1121 AA;  126460 MW;  AB09166AE6798232 CRC64;
     MLRRFSSTFK KKGDRESKQN GTASSSSAAV ANTNNNDNKR HSKISAARKS SSDDDRNEKK
     GNSVSPFEKY ASVLHASRSP IPNQTGDGAY LEHEHTTSLL QDARHLGFKD FKTLKEVIES
     KLPGGQLIDD KTMLMERIIQ LVSRLPHNSK HREELTNAFL TELWDSLPHP PLSYMGNDYA
     YRSADGSNNN PTLPRLGAAN TLYARTIPPL IIQPGGLPDP GLVFDTLFAR QTFKPHPNKV
     SSVFFYWASL IIHDIFQTDY KNPNMNKTSG YLDLSILYGD VQEEQNLIRT FKDGKLKPDS
     FSEPRLQAFP ATCCVLMVML NRFHNYAVEQ LAAINENGRF TKPADNLSEE EAKKAWAKYD
     EDLFQTGRLI TCGLYINITL YDYLRTIVNL NRTNSTWCLD PRAQMEGSHT APSGLGNQCS
     VEFNLAYRWH SATSATDEKW TEDVYERLMG KPASEVSMTE LLMGLGKYQA ELPKDPSKRT
     FADLERQADG RFKDEDLVNL LVNAVEDVAG SFGARNVPKV LKNVEILGII QSRKWNVGSL
     NEFRKFFGLK PYETFEEINS DPDVAESLRS LYDHPDFVEL YPGIVAEEAK QPMVPGVGIA
     PTYTISRAVL SDAVALVRGD RFYTIDYNPR NLTNWGYSEV RYDLSINQGC IFYKLATRAF
     PNWFKPDSIY AHYPMTIPSE NRKIMKDLGR EIHYSWDRPQ YTPPRVDLVS YSNAKLVAEQ
     QNQFRAAWGD TVEFVFGKAS KEFKLYQDSA FIQKHADVMS KLLNKEEWHR SVKEFYEDIT
     AKLLEDKTRR FGGINQVDIT NDVGNLTPVI FAANVFSLPL KSKENPRGIY TEHEMFKVLA
     ALYNCLYFDI DKTKSYPLHH ASQAVGEPLG KALEANVKAL GGSSLLSGIF RSFRENKNAL
     KEYGVHLTKQ LLENGLGAHE IAWAQFLPTV IAMVPAQAQA FTQIVDFYLS KEGSKHLPAI
     QRLAKQDTKK SDEQLLHYCL EAVRLNDMSG LYRQSETTLA VTDEAVEVTI QPGDKVFVSF
     AKANRDASVF PDPAEVRLDR PMNSYINPTL GPHGFLSKET SHIALTAMLR AVGRLNNLRV
     APGVQGQLKK IPQPGGYSAY LREDHGSYSI FPTTFRVQYD A
//