LKHA4_SCHPO
ID LKHA4_SCHPO Reviewed; 612 AA.
AC O94544;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
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=lap2; ORFNames=SPCC1322.05c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
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:0000269|PubMed:16823372}. Nucleus
CC {ECO:0000269|PubMed:16823372}.
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; CU329672; CAA22858.1; -; Genomic_DNA.
DR PIR; T40936; T40936.
DR RefSeq; NP_588133.1; NM_001023123.2.
DR AlphaFoldDB; O94544; -.
DR SMR; O94544; -.
DR BioGRID; 275494; 2.
DR STRING; 4896.SPCC1322.05c.1; -.
DR MEROPS; M01.034; -.
DR iPTMnet; O94544; -.
DR MaxQB; O94544; -.
DR PaxDb; O94544; -.
DR PRIDE; O94544; -.
DR EnsemblFungi; SPCC1322.05c.1; SPCC1322.05c.1:pep; SPCC1322.05c.
DR GeneID; 2538917; -.
DR KEGG; spo:SPCC1322.05c; -.
DR PomBase; SPCC1322.05c; lap2.
DR VEuPathDB; FungiDB:SPCC1322.05c; -.
DR eggNOG; KOG1047; Eukaryota.
DR HOGENOM; CLU_014505_1_2_1; -.
DR InParanoid; O94544; -.
DR OMA; YHPICRQ; -.
DR PhylomeDB; O94544; -.
DR Reactome; R-SPO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-SPO-6798695; Neutrophil degranulation.
DR Reactome; R-SPO-9018676; Biosynthesis of D-series resolvins.
DR Reactome; R-SPO-9018681; Biosynthesis of protectins.
DR Reactome; R-SPO-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-SPO-9020265; Biosynthesis of aspirin-triggered D-series resolvins.
DR Reactome; R-SPO-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR PRO; PR:O94544; -.
DR Proteomes; UP000002485; Chromosome III.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0000328; C:fungal-type vacuole lumen; IDA:PomBase.
DR GO; GO:0005771; C:multivesicular body; IDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0061957; C:NVT complex; IPI:PomBase.
DR GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004301; F:epoxide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; ISO:PomBase.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0120113; P:cytoplasm to vacuole transport by the NVT pathway; IMP:PomBase.
DR GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISO:PomBase.
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..612
FT /note="Leucine aminopeptidase 2"
FT /id="PRO_0000095128"
FT ACT_SITE 295
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 382
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 136..138
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 265..270
FT /ligand="substrate"
FT /evidence="ECO:0000250"
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 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ SEQUENCE 612 AA; 69522 MW; 19D3DFFC5CE2A341 CRC64;
MKLRLDPSTQ SNYHDVSISK LDWHARIDFD QELLHGKVSF VIQSARVSQA LSHIILDTSY
LEIKNVTIND IPTPFRVDKR RGFLGSALHI VPADEIPSSK SCILTILYST TKDCTALQFL
KPEQTIGGKF PYVFSECQAI HARSFIPCQD TPSVKVPCTF KIRSKLPVIA SGIPCGTANF
CNGSLEYLFE QKNPIPSYLF CILSGDLAST NIGPRSSVYT EPGNLLACKY EFEHDMENFM
EAAEQLTLPY CWTRYDFVIL PPSFPYGGME NPNATFATPT LIAGDRSNVN VIAHELAHSW
SGNLVTNESW QCFWLNEGMT VFLERKILGR LYGEPTRQFE AIIGWGELEE SVKLLGEDSE
YTKLIQNLEG RDPDDAFSTV PYEKGSNFLY EIERVIGGPS VFEPFLPFYF RKFAKSTVNE
VKFKHALYEY FSPLGLASKL DSIDWDTWYH APGMPPVKPH FDTTLADPCY KLAESWTNSA
KNSDDPSKFS SKDIENWSAG QKSLFLDVVY EAVSFPHNYI KRMGDVYSFA ESKNAELSFR
FFKLALKSKY KPLYNTIAER VGSVGRMKFV RPIFRLLNEA DRAFAIETFE KYKHFYHKIC
ASQVEKDLGL SE
