LKHA4_YEAS7
ID LKHA4_YEAS7 Reviewed; 671 AA.
AC A6ZS33;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 ORFNames=SCY_4744;
OS Saccharomyces cerevisiae (strain YJM789) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=307796;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=YJM789;
RX PubMed=17652520; DOI=10.1073/pnas.0701291104;
RA Wei W., McCusker J.H., Hyman R.W., Jones T., Ning Y., Cao Z., Gu Z.,
RA Bruno D., Miranda M., Nguyen M., Wilhelmy J., Komp C., Tamse R., Wang X.,
RA Jia P., Luedi P., Oefner P.J., David L., Dietrich F.S., Li Y., Davis R.W.,
RA Steinmetz L.M.;
RT "Genome sequencing and comparative analysis of Saccharomyces cerevisiae
RT strain YJM789.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:12825-12830(2007).
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 -!- ACTIVITY REGULATION: Inhibited by 3-(4-benzyloxyphenyl)-2-(R)-amino-1-
CC propanethiol (thioamine) and N-hydroxy-N-(2-(S)-amino-3-(4-
CC benzyloxyphenyl)propyl)-5-carboxypen-tanamide (hydroxamic acid). The
CC aminopeptidase activity is stimulated by LTA(4).
CC {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; AAFW02000067; EDN62765.1; -; Genomic_DNA.
DR AlphaFoldDB; A6ZS33; -.
DR SMR; A6ZS33; -.
DR MEROPS; M01.034; -.
DR PRIDE; A6ZS33; -.
DR EnsemblFungi; EDN62765; EDN62765; SCY_4744.
DR HOGENOM; CLU_014505_1_1_1; -.
DR Proteomes; UP000007060; 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 Zinc.
FT CHAIN 1..671
FT /note="Leucine aminopeptidase 2"
FT /id="PRO_0000324943"
FT ACT_SITE 341
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 429
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 184..186
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 311..316
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 340
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 363
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ SEQUENCE 671 AA; 77353 MW; 454E40F030BF28FA CRC64;
MFLLPFVIRH SSSIYLPTLR FRGLLTVISR NIHISTPHKM LPLSIEQRRP SRSPEYDQST
LSNYKDFAVL HTDLNLSVSF EKSAISGSVT FQLKKLHEGK NKSDELHLDT SYLDVQEVHI
DGSKADFQIE QRKEPLGSRL VINNASCNDN FTLNIQFRTT DKCTALQWLN SKQTKGGKPY
VFSQLEAIHA RSLFPCFDTP SVKSTFTASI ESPLPVVFSG IRIEDTSKDT NIYRFEQKVP
IPAYLIGIAS GDLSSAPIGP RSTVYTEPFR LKDCQWEFEN DVEKFIQTAE KIIFEYEWGT
YDILVNVDSY PYGGMESPNM TFATPTLIAH DRSNIDVIAH ELAHSWSGNL VTNCSWNHFW
LNEGWTVYLE RRIIGAIHGE PTRHFSALIG WSDLQNSIDS MKDPERFSTL VQNLNDNTDP
DDAFSTVPYE KGFNLLFHLE TILGGKAEFD PFIRHYFKKF AKKSLDTFQF LDTLYEFYPE
KKEILDSVDW ETWLYKPGMP PRPHFITALA DNVYQLADKW VEMAQHLKTT EDFRSEFNAI
DIKDFNSNQL VLFLETLTQN GHSNKKPKDF DWAKFPVASR ALLDIYQDNI VKSQNAEVVF
KMFKFQIFAK LQEEYKHLAD WLGTVGRMKF VRPGYRLLNS VDRRLALATF DKFKDTYHPI
CKALVKQDLG L
