ID   LKA41_PICGU             Reviewed;         615 AA.
AC   A5DME6;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 2.
DT   03-AUG-2022, entry version 85.
DE   RecName: Full=Leucine aminopeptidase 2-1;
DE            EC=3.4.11.-;
DE   AltName: Full=Epoxide hydrolase;
DE            EC=3.3.2.10;
DE   AltName: Full=Leukotriene A-4 hydrolase homolog 1;
DE            Short=LTA-4 hydrolase 1;
GN   ORFNames=PGUG_04447;
OS   Meyerozyma guilliermondii (strain ATCC 6260 / CBS 566 / DSM 6381 / JCM 1539
OS   / NBRC 10279 / NRRL Y-324) (Yeast) (Candida guilliermondii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Debaryomycetaceae; Meyerozyma.
OX   NCBI_TaxID=294746;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 6260 / CBS 566 / DSM 6381 / JCM 1539 / NBRC 10279 / NRRL Y-324;
RX   PubMed=19465905; DOI=10.1038/nature08064;
RA   Butler G., Rasmussen M.D., Lin M.F., Santos M.A.S., Sakthikumar S.,
RA   Munro C.A., Rheinbay E., Grabherr M., Forche A., Reedy J.L., Agrafioti I.,
RA   Arnaud M.B., Bates S., Brown A.J.P., Brunke S., Costanzo M.C.,
RA   Fitzpatrick D.A., de Groot P.W.J., Harris D., Hoyer L.L., Hube B.,
RA   Klis F.M., Kodira C., Lennard N., Logue M.E., Martin R., Neiman A.M.,
RA   Nikolaou E., Quail M.A., Quinn J., Santos M.C., Schmitzberger F.F.,
RA   Sherlock G., Shah P., Silverstein K.A.T., Skrzypek M.S., Soll D.,
RA   Staggs R., Stansfield I., Stumpf M.P.H., Sudbery P.E., Srikantha T.,
RA   Zeng Q., Berman J., Berriman M., Heitman J., Gow N.A.R., Lorenz M.C.,
RA   Birren B.W., Kellis M., Cuomo C.A.;
RT   "Evolution of pathogenicity and sexual reproduction in eight Candida
RT   genomes.";
RL   Nature 459:657-662(2009).
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; CH408159; EDK40349.2; -; Genomic_DNA.
DR   RefSeq; XP_001483718.1; XM_001483668.1.
DR   AlphaFoldDB; A5DME6; -.
DR   SMR; A5DME6; -.
DR   STRING; 4929.XP_001483718.1; -.
DR   MEROPS; M01.034; -.
DR   EnsemblFungi; EDK40349; EDK40349; PGUG_04447.
DR   GeneID; 5125528; -.
DR   KEGG; pgu:PGUG_04447; -.
DR   VEuPathDB; FungiDB:PGUG_04447; -.
DR   eggNOG; KOG1047; Eukaryota.
DR   HOGENOM; CLU_014505_1_1_1; -.
DR   InParanoid; A5DME6; -.
DR   OMA; YHPICRQ; -.
DR   OrthoDB; 775595at2759; -.
DR   Proteomes; UP000001997; Unassembled WGS sequence.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0043171; P:peptide catabolic process; ISS:UniProtKB.
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..615
FT                   /note="Leucine aminopeptidase 2-1"
FT                   /id="PRO_0000324936"
FT   ACT_SITE        291
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        380
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         137..139
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         261..266
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         290
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         294
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         313
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ   SEQUENCE   615 AA;  70392 MW;  B41C65A30CC891C7 CRC64;
     MLRRPKVSPE LDPSTLSNYG DFIVHKTQLD LAVDFDKNRV SSCVSLNVTN RTNTHQVVLD
     SSYLVIHSAS INGISTPFDV AERQTLGSKV TIKIPPEMKI SELTITIESE TTYECTALQF
     LPAEATDGGV GPYLFSQCQA IHARSLFPCF DTPAVKCPYE MSVTSPYPSV MSGRPLGVSG
     NMYRFSQPVP IPSYLVAVAS GDIKSAPIGP RSSVYCEPLK LEVCQHEFQA DMEHFLQAAE
     SLVFKYEWER YDALVLPSSF PYGGMENPNI TFVTPTLISG DRENVDVIAH ELAHSWSGNL
     VTNCSWEHFW LNEGWTVYLE RRILGKLHGN ATRDFSAIIG WTDLENSIAA MGPSAERWSM
     LVHNLKDGSD PDDAFSTVPY EKGSTLLYHI ETLIGQEKFD KFIPHYFHTF RYKSLDTYQF
     IDCLYSFFAD FKSVLDTIDW ESWLYKPGMP PVKPDFDTSM VDQCYQLADK WYHHSLKNKF
     HKFSSEDIKS FTANQSVVFL DTLIAFDKLD FKWKHHLDAL NTMASVYQEY SKSTNAEVLF
     RWYVLQVTGH NQEYYSRLGE WLGTVGRMKF VRPGYVLLNK VDRSMALHYF EKFHNRYHAI
     CKSMVRRDWD LIKTK