LKHA4_AJECN
ID LKHA4_AJECN Reviewed; 623 AA.
AC A6RCT2;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 88.
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=HCAG_07440;
OS Ajellomyces capsulatus (strain NAm1 / WU24) (Darling's disease fungus)
OS (Histoplasma capsulatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Ajellomycetaceae; Histoplasma;
OC unclassified Histoplasma.
OX NCBI_TaxID=2059318;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NAm1 / WU24;
RX PubMed=19717792; DOI=10.1101/gr.087551.108;
RA Sharpton T.J., Stajich J.E., Rounsley S.D., Gardner M.J., Wortman J.R.,
RA Jordar V.S., Maiti R., Kodira C.D., Neafsey D.E., Zeng Q., Hung C.-Y.,
RA McMahan C., Muszewska A., Grynberg M., Mandel M.A., Kellner E.M.,
RA Barker B.M., Galgiani J.N., Orbach M.J., Kirkland T.N., Cole G.T.,
RA Henn M.R., Birren B.W., Taylor J.W.;
RT "Comparative genomic analyses of the human fungal pathogens Coccidioides
RT and their relatives.";
RL Genome Res. 19:1722-1731(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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDN10979.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CH476662; EDN10979.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001538018.1; XM_001537968.1.
DR AlphaFoldDB; A6RCT2; -.
DR SMR; A6RCT2; -.
DR STRING; 339724.A6RCT2; -.
DR MEROPS; M01.034; -.
DR EnsemblFungi; EDN10979; EDN10979; HCAG_07440.
DR GeneID; 5444402; -.
DR KEGG; aje:HCAG_07440; -.
DR HOGENOM; CLU_014505_1_1_1; -.
DR OrthoDB; 775595at2759; -.
DR Proteomes; UP000009297; 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..623
FT /note="Leucine aminopeptidase 2"
FT /id="PRO_0000324916"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 307
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 394
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 145..147
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 277..282
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ SEQUENCE 623 AA; 70379 MW; 00C7317297839194 CRC64;
MRRCTKNSRS TNPPRDPNTL SNYNAFRTTH TTVNFDILFE KQKLTGNVMH KLISLTNLEA
REVILDSSFL NIHDVKVDGK QSKFELLPRQ EPYGSALKIP LAEGVALSKT LDIDITVETT
EKCTALQWLT PAQTSTQKHP YMFTQCQAIH ARSIFPCQDT PDVKAVIDFN ISSPLPVIAS
GVPVNDVSSS SSKSKNKVYK FHQKVPIPTY LFAMASGEIA EAPIGPRSRV AASPDKLEEC
KWELEADTEK FMQAIDKIIF PYIWGEYNVL ILPPSFPYGG MENPIFTFAT PSVISKDRQN
VDVIAHELAH SWSGNLVTNA SWEHFWLNEG WTTYLERRIL AAVHGEPYRH FSAIIGWKAL
TESVERYGKD HEFTKLVVDL KGKDPDDAFS SVPYEKGFNF LFYLENLIGK DKFDKFIPHY
FTKYKEASLD SYEFKSSILS FFSSDSEAHA LLTSFDWDKW FYSPGLPPKP DFDTSLVDIV
YALAQKWRTA SESGFSPSAV DVNGLVANQL VVFLEQVLVF EKPLSAEQSK LMGDKYGLAK
SENAEVLNMY FQVGLKAGDK SVIEPTAAFL SSIGRMKYVR PLYRALDKLD RNIAIEVFEK
NKSFYHPICR GLVQKDLFGN KGS
