ID   LKHA4_CHILA             Reviewed;         611 AA.
AC   Q6S9C8;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 89.
DE   RecName: Full=Leukotriene A-4 hydrolase;
DE            Short=LTA-4 hydrolase;
DE            EC=3.3.2.6;
DE   AltName: Full=Leukotriene A(4) hydrolase;
GN   Name=LTA4H;
OS   Chinchilla lanigera (Long-tailed chinchilla) (Chinchilla villidera).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha;
OC   Chinchillidae; Chinchilla.
OX   NCBI_TaxID=34839;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Middle ear mucosa;
RA   Erdos G., Hu F.Z., Donfack J., Ahmed A.I., Preston R.A., Post J.C.,
RA   Ehrlich G.D.;
RT   "The chinchilla leukotriene A4 hydrolase gene is expressed in normal middle
RT   ear mucosa.";
RL   Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Epoxide hydrolase that catalyzes the final step in the
CC       biosynthesis of the pro-inflammatory mediator leukotriene B4. Has also
CC       aminopeptidase activity (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + leukotriene A4 = leukotriene B4; Xref=Rhea:RHEA:22324,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:57461, ChEBI:CHEBI:57463; EC=3.3.2.6;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Inhibited by bestatin. Subject to suicide
CC       inhibition by leukotriene A4 (By similarity). {ECO:0000250}.
CC   -!- PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- PTM: Phosphorylation at Ser-416 inhibits enzymatic activity.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR   EMBL; AY462137; AAR26536.1; -; mRNA.
DR   RefSeq; NP_001269293.1; NM_001282364.1.
DR   AlphaFoldDB; Q6S9C8; -.
DR   SMR; Q6S9C8; -.
DR   MEROPS; M01.004; -.
DR   GeneID; 102007852; -.
DR   CTD; 4048; -.
DR   OrthoDB; 775595at2759; -.
DR   UniPathway; UPA00878; -.
DR   Proteomes; UP000694398; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; 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:0004463; F:leukotriene-A4 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:0019370; P:leukotriene biosynthetic process; 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   2: Evidence at transcript level;
KW   Acetylation; Cytoplasm; Hydrolase; Leukotriene biosynthesis; Metal-binding;
KW   Metalloprotease; Phosphoprotein; Protease; Reference proteome; Zinc.
FT   CHAIN           1..611
FT                   /note="Leukotriene A-4 hydrolase"
FT                   /id="PRO_0000095123"
FT   ACT_SITE        297
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        384
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         135..137
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         267..272
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         296
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         300
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         319
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         564..566
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            376
FT                   /note="Essential for epoxide hydrolase activity, but not
FT                   for aminopeptidase activity"
FT                   /evidence="ECO:0000250"
FT   SITE            379
FT                   /note="Covalently modified during suicide inhibition by
FT                   leukotrienes"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         73
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09960"
FT   MOD_RES         337
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09960"
FT   MOD_RES         416
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P09960"
FT   MOD_RES         573
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09960"
SQ   SEQUENCE   611 AA;  69213 MW;  3E358988E8B98044 CRC64;
     MPEVEDTCFL TSPITVCRTK HLHLRCSVDF SSRALTGIAA LTIQSQEDNL RSLVLDTKAL
     TIEKVVINGQ EVKYALGERQ SYKGSPMEIS LPIALSKNQE VVIEISFETS PKSSALQWLT
     PEQTSGKEHP YLFSQCQAIH CRAVLPCQDT PSVKLTYTAE VSVPKELVAL MSAVRDGETP
     DPEDPSRKIY KFNQKVPIPC YLIALVVGAL ESRKIGPRTL VWSEKEQVEK SAYEFSETES
     MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH
     SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FHALGGWGEL QNTIKTFGET
     HPFTKLVVDL TDVDPDVAYS SVPYEKGFAL LFHLEQLLGG PEVFLGFLKA YVERFSYKSI
     TTDDWKNFLY SHFKDKVDIL NQVDWNAWLY SPGLPPVKPN YDMTLTNACI ALSQRWITAK
     EEDLNTFNAT DLKDLSTHQV NEFLAQVLQQ APLPLGHVKR MQEVYNFNAV NNSEIRFRWL
     RLCIQSKWEE AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAIRTYQ AHKASMHPVT
     AMLVGKDLKV D