ID   LKHA4_CANGA             Reviewed;         652 AA.
AC   Q6FTM0;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 112.
DE   RecName: Full=Leucine aminopeptidase 2;
DE            EC=3.4.11.-;
DE   AltName: Full=Epoxide hydrolase;
DE            EC=3.3.2.10;
DE   AltName: Full=Leukotriene A-4 hydrolase homolog;
DE            Short=LTA-4 hydrolase;
GN   OrderedLocusNames=CAGL0G01430g;
OS   Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL
OS   Y-65) (Yeast) (Torulopsis glabrata).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Nakaseomyces;
OC   Nakaseomyces/Candida clade.
OX   NCBI_TaxID=284593;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
CC   -!- FUNCTION: Aminopeptidase that preferentially cleaves di- and
CC       tripeptides. Also has low epoxide hydrolase activity (in vitro). Can
CC       hydrolyze the epoxide leukotriene LTA(4) but it forms preferentially
CC       5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid rather than the cytokine
CC       leukotriene B(4) as the product compared to the homologous mammalian
CC       enzyme (in vitro). {ECO:0000250|UniProtKB:Q10740}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an epoxide + H2O = an ethanediol; Xref=Rhea:RHEA:19037,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:32955, ChEBI:CHEBI:140594;
CC         EC=3.3.2.10; Evidence={ECO:0000250|UniProtKB:Q10740};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q10740};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q10740};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q10740}. Nucleus
CC       {ECO:0000250|UniProtKB:Q10740}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR   EMBL; CR380953; CAG59351.1; -; Genomic_DNA.
DR   RefSeq; XP_446424.1; XM_446424.1.
DR   AlphaFoldDB; Q6FTM0; -.
DR   SMR; Q6FTM0; -.
DR   STRING; 5478.XP_446424.1; -.
DR   MEROPS; M01.034; -.
DR   PRIDE; Q6FTM0; -.
DR   EnsemblFungi; CAG59351; CAG59351; CAGL0G01430g.
DR   GeneID; 2888012; -.
DR   KEGG; cgr:CAGL0G01430g; -.
DR   CGD; CAL0129700; CAGL0G01430g.
DR   VEuPathDB; FungiDB:CAGL0G01430g; -.
DR   eggNOG; KOG1047; Eukaryota.
DR   HOGENOM; CLU_014505_1_1_1; -.
DR   InParanoid; Q6FTM0; -.
DR   Proteomes; UP000002428; Chromosome G.
DR   GO; GO:0000328; C:fungal-type vacuole lumen; IEA:EnsemblFungi.
DR   GO; GO:0005771; C:multivesicular body; IEA:EnsemblFungi.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0061957; C:NVT complex; IEA:EnsemblFungi.
DR   GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0004301; F:epoxide hydrolase activity; ISS:UniProtKB.
DR   GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0044255; P:cellular lipid metabolic process; IEA:EnsemblFungi.
DR   GO; GO:0120113; P:cytoplasm to vacuole transport by the NVT pathway; IEA:EnsemblFungi.
DR   GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR   GO; GO:0030163; P:protein catabolic process; IEA:EnsemblFungi.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd09599; M1_LTA4H; 1.
DR   Gene3D; 1.10.390.10; -; 1.
DR   Gene3D; 1.25.40.320; -; 1.
DR   Gene3D; 2.60.40.1730; -; 1.
DR   InterPro; IPR045357; Aminopeptidase_N-like_N.
DR   InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR012777; LTA4H.
DR   InterPro; IPR038502; M1_LTA-4_hydro/amino_C_sf.
DR   InterPro; IPR034015; M1_LTA4H.
DR   InterPro; IPR001930; Peptidase_M1.
DR   InterPro; IPR015211; Peptidase_M1_C.
DR   InterPro; IPR014782; Peptidase_M1_dom.
DR   InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR   PANTHER; PTHR45726; PTHR45726; 1.
DR   Pfam; PF09127; Leuk-A4-hydro_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   Pfam; PF17900; Peptidase_M1_N; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SMART; SM01263; Leuk-A4-hydro_C; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   SUPFAM; SSF63737; SSF63737; 1.
DR   TIGRFAMs; TIGR02411; leuko_A4_hydro; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Hydrolase; Metal-binding; Metalloprotease; Nucleus; Protease;
KW   Reference proteome; Zinc.
FT   CHAIN           1..652
FT                   /note="Leucine aminopeptidase 2"
FT                   /id="PRO_0000324925"
FT   ACT_SITE        323
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        411
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         165..167
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         293..298
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         322
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         326
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         345
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ   SEQUENCE   652 AA;  74823 MW;  4AD4BB847DEF880B CRC64;
     MINRLIQRIV PFSRPLSTVK KTMLTPFLES KRPQQSPEYD YSTLSNYKSF QIKHTTLNFL
     LSFEKSTVSG DVVFDLTTLK EAVKHIDLDT SYLDVNEVLV DDKPVEFKIE ERKQPLGSKL
     VIAAELEAER QFKLRVKFST TKDCTALQWL TPQQTSGDKP YMFSQLEAIH ARALFPCFDT
     PSYKSTFTAN IESTLPVVFS GIATGSTPNG ESTVYHFKQD IPIPAYLVGI ASGDLVSASI
     GPRSKVYTEP HRLDDCVWEF SNDVEKFIKT AENLIFDYEW GTYDILVNVD SYPYGGMESP
     NMTFATPTLI AHDKTNIDVI AHELAHSWSG NLVTNCSWNH FWLNEGWTVY IERRIVGALH
     GEPTRHFSAL IGWSDLENSI NSMRNPEKFS TLVQNLNDGT DPDDAFSTVP YEKGFNLLFH
     LETVLGGPQE FDPFIRHYFK KFARQSLDTF QFLDTLFEFF ENKREILENV DWETWLFKPG
     MPPKPQFITT MADNVFSLVN KWIVKAQELK TTEEFSKEFS ESDLSEFNSN QVVLFLEELV
     AQNCVPVESK IEWSKYSVAS ESLLSIYKKQ VTESQNAEVV FKNYKFQTTA RIQPSYQQLA
     NWLGTVGRMK FVRPGYRLLN AVDRDLAIAT FEKLKDTYHP ICKQLVKQDL EL