LKHA4_DICDI
ID LKHA4_DICDI Reviewed; 606 AA.
AC P52922; Q55BR5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Leucine aminopeptidase;
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=lkhA; ORFNames=DDB_G0269148;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 291-606.
RC STRAIN=AX3;
RA Jho E., Kopachik W.;
RT "Primary sequence and developmental regulation of Dictyostelium discoideum
RT cDNA encoding homolog of the human leukotriene A4 hydrolase.";
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
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}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AAFI02000005; EAL71924.1; -; Genomic_DNA.
DR EMBL; U27538; AAA70101.1; -; mRNA.
DR RefSeq; XP_646766.1; XM_641674.1.
DR AlphaFoldDB; P52922; -.
DR SMR; P52922; -.
DR STRING; 44689.DDB0191291; -.
DR MEROPS; M01.A32; -.
DR PaxDb; P52922; -.
DR EnsemblProtists; EAL71924; EAL71924; DDB_G0269148.
DR GeneID; 8617739; -.
DR KEGG; ddi:DDB_G0269148; -.
DR dictyBase; DDB_G0269148; lkhA.
DR eggNOG; KOG1047; Eukaryota.
DR HOGENOM; CLU_014505_1_2_1; -.
DR InParanoid; P52922; -.
DR OMA; YHPICRQ; -.
DR PhylomeDB; P52922; -.
DR Reactome; R-DDI-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-9018676; Biosynthesis of D-series resolvins.
DR Reactome; R-DDI-9018681; Biosynthesis of protectins.
DR Reactome; R-DDI-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-DDI-9020265; Biosynthesis of aspirin-triggered D-series resolvins.
DR Reactome; R-DDI-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR PRO; PR:P52922; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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:0019370; P:leukotriene biosynthetic process; IEA:UniProtKB-KW.
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; 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 PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Hydrolase; Leukotriene biosynthesis; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Zinc.
FT CHAIN 1..606
FT /note="Leucine aminopeptidase"
FT /id="PRO_0000095127"
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 132..134
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"
FT CONFLICT 291..292
FT /note="EI -> HE (in Ref. 2; AAA70101)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 606 AA; 68469 MW; C851065439B1C115 CRC64;
MDPSSLSNPQ ECKVTSLNLV LSVNFEKSQL QGYVEVASQI VKEGTESLIL DTNQLEISHC
NDVTSNPINF KLSEEHKVFG KALIISIPEG LRSVGKEFIV RVYYNTTVDS NALQWLTKDQ
TAGKLHPYLF SQCQAIHARS LVPCQDSPSN KVKYQAEITV PKPLTALMSA LSTGKTESTD
SSVFTFTQEI PIPTYLIAIV VGDLESRVIG PRSKVWSEPS MVAAAEYEFA NTEKFIAVGE
DLLTPYVWGR YDILLLPPSF PYGGMENPLL TFVTPTLLAG DRSLEGVVAH EIAHSWCGNL
VTNKYWSEFF LNEGFTVFVE RKILGRLYGE EMFDFEAMNG LKHLHDDVDL FTHKHQEELT
ALIPNLNGID PDDAFSSVPY EKGFNLLCYL QSLVGVADFE AWLKSYISKF SYQSIVATQM
KDYFIEYFTE KGKSEQISVV NWNDWFNKPG MPIEQVVFVS PAAKVAKDLA EITWIKDQGV
NATKDDIKSF KTQQIILFLD TLIHSTSEKP LSVDVLEKMD SLYGFTDVVN SEYKFRWQTL
CLHSGLKRIE PKVVEFLISQ GRMKFVRPLY RELNKVNPEL AKSTFNKYKS QYHIIASKMV
AKDLGL
