ID   LKHA4_NEUCR             Reviewed;         667 AA.
AC   Q7S785;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   19-MAR-2014, sequence version 2.
DT   03-AUG-2022, entry version 124.
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   Name=ara-1; ORFNames=NCU06732;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
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; CM002240; EAA31424.2; -; Genomic_DNA.
DR   RefSeq; XP_960660.2; XM_955567.3.
DR   AlphaFoldDB; Q7S785; -.
DR   SMR; Q7S785; -.
DR   STRING; 5141.EFNCRP00000006630; -.
DR   MEROPS; M01.034; -.
DR   EnsemblFungi; EAA31424; EAA31424; NCU06732.
DR   GeneID; 3876807; -.
DR   KEGG; ncr:NCU06732; -.
DR   VEuPathDB; FungiDB:NCU06732; -.
DR   HOGENOM; CLU_014505_1_1_1; -.
DR   InParanoid; Q7S785; -.
DR   Proteomes; UP000001805; Chromosome 2, Linkage Group V.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
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..667
FT                   /note="Leucine aminopeptidase 2"
FT                   /id="PRO_0000324934"
FT   ACT_SITE        348
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        436
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         188..190
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         318..323
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         347
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         351
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         370
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ   SEQUENCE   667 AA;  74817 MW;  A503713C32CBC1E1 CRC64;
     MWGRGFLQRA RFAQLSPSSS SSRSLLSAAS AAPPNLLYSH YQRGRWFGCS TANMAPVRDP
     NTLSNYDAWR TRHTTANLKI DFTAKCLRGS VILELESQTD KASKEIVLDS SYVTVNSIKL
     NSAPSLWETK ARTEPNGSPV HIAVPEGAAK GEVVKVEIEL ATTDKCTALQ WLTPAQTSDK
     AAPFMFSQCQ AIHARSLFPC QDTPDVKSTY DFNITSPYVV VASGVPVPDE TKDLGEEKLY
     KFQQKVPIPS YLFALSSGEI ASAPVGKRSC VCTGPNELKA SQWELEGDMD KFLEAAEKIV
     FPYRWGEYNV LVLPPSFPYG GMENPIFTFA TPTIISGDKQ NIDVIAHELA HSWSGNLVTS
     CSWEHFWLNE GWTMYLERRI LASIHGGDAH FDFSAIRGWK ALEEAIKEYG EDHEFTKLCI
     SHKGIDPDDA FSTVPYEKGF HFVWSLDRLV GRENFDKFIP YYFGKWSNKS LDSYEFKDTF
     LEFFSAPEYS DLKDKIASID WEGRFHSTGL PPKPEFDTSL ADVCYELAEK WKSKDFTPSP
     SDVASWTGNQ VLVFLNAVQD FEEPLTVEQS QALGKAYGLS ESKNAELKAA YYHIAMRSKD
     ASAYQGVADL LGEVGRMKFV RPLFRGLNKV DRELALKTFE KNREFYHPIC RQMVEKDLGV
     SEAANSS