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Database: UniProt
Entry: LKHA4_MOUSE
LinkDB: LKHA4_MOUSE
Original site: LKHA4_MOUSE 
ID   LKHA4_MOUSE             Reviewed;         611 AA.
AC   P24527; Q3UY71; Q8VDR8;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   29-OCT-2014, entry version 141.
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Spleen;
RX   PubMed=1710117; DOI=10.1016/0006-291X(91)90459-K;
RA   Medina J.F., Raadmark O., Funk C.D., Haeggstroem J.Z.;
RT   "Molecular cloning and expression of mouse leukotriene A4 hydrolase
RT   cDNA.";
RL   Biochem. Biophys. Res. Commun. 176:1516-1524(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   MUTAGENESIS OF ZINC LIGANDS.
RX   PubMed=1881903; DOI=10.1073/pnas.88.17.7620;
RA   Medina J.F., Wetterholm A., Raadmark O., Shapiro R., Haeggstroem J.Z.,
RA   Vallee B.L., Samuelsson B.;
RT   "Leukotriene A4 hydrolase: determination of the three zinc-binding
RT   ligands by site-directed mutagenesis and zinc analysis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:7620-7624(1991).
RN   [5]
RP   MUTAGENESIS OF TYR-384, CATALYTIC ACTIVITY, FUNCTION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION.
RX   PubMed=9287304; DOI=10.1074/jbc.272.37.23057;
RA   Andberg M.B., Hamberg M., Haeggstrom J.Z.;
RT   "Mutation of tyrosine 383 in leukotriene A4 hydrolase allows
RT   conversion of leukotriene A4 into 5S,6S-dihydroxy-7,9-trans-11,14-cis-
RT   eicosatetraenoic acid. Implications for the epoxide hydrolase
RT   mechanism.";
RL   J. Biol. Chem. 272:23057-23063(1997).
CC   -!- FUNCTION: Epoxide hydrolase that catalyzes the final step in the
CC       biosynthesis of the proinflammatory mediator leukotriene B4. Has
CC       also aminopeptidase activity. {ECO:0000269|PubMed:9287304}.
CC   -!- CATALYTIC ACTIVITY: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-
CC       7,9,11,14-tetraenoate + H(2)O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-
CC       dihydroxyicosa-6,8,10,14-tetraenoate.
CC       {ECO:0000269|PubMed:9287304}.
CC   -!- COFACTOR: Binds 1 zinc ion per subunit.
CC   -!- ENZYME REGULATION: Inhibited by bestatin. Subject to suicide
CC       inhibition by leukotriene A4. {ECO:0000269|PubMed:9287304}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5 uM for leukotriene A4 {ECO:0000269|PubMed:9287304};
CC         Vmax=1030 nmol/min/mg enzyme for leukotriene A4
CC         {ECO:0000269|PubMed:9287304};
CC   -!- PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
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; M63848; AAB59675.1; -; mRNA.
DR   EMBL; AK134931; BAE22342.1; -; mRNA.
DR   EMBL; BC021417; AAH21417.1; -; mRNA.
DR   CCDS; CCDS24125.1; -.
DR   PIR; JN0066; JN0066.
DR   RefSeq; NP_032543.2; NM_008517.2.
DR   UniGene; Mm.271071; -.
DR   ProteinModelPortal; P24527; -.
DR   SMR; P24527; 6-610.
DR   IntAct; P24527; 2.
DR   MINT; MINT-1868661; -.
DR   STRING; 10090.ENSMUSP00000016033; -.
DR   ChEMBL; CHEMBL3738; -.
DR   MEROPS; M01.004; -.
DR   PhosphoSite; P24527; -.
DR   MaxQB; P24527; -.
DR   PaxDb; P24527; -.
DR   PRIDE; P24527; -.
DR   Ensembl; ENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889.
DR   GeneID; 16993; -.
DR   KEGG; mmu:16993; -.
DR   UCSC; uc007gur.1; mouse.
DR   CTD; 4048; -.
DR   MGI; MGI:96836; Lta4h.
DR   eggNOG; COG0308; -.
DR   GeneTree; ENSGT00530000063003; -.
DR   HOGENOM; HOG000293296; -.
DR   HOVERGEN; HBG001274; -.
DR   InParanoid; P24527; -.
DR   KO; K01254; -.
DR   OMA; SPASVCQ; -.
DR   OrthoDB; EOG7SJD42; -.
DR   TreeFam; TF300758; -.
DR   Reactome; REACT_215561; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR   UniPathway; UPA00878; -.
DR   NextBio; 291088; -.
DR   PRO; PR:P24527; -.
DR   Bgee; P24527; -.
DR   CleanEx; MM_LTA4H; -.
DR   Genevestigator; P24527; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
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:0044822; F:poly(A) RNA binding; IEA:Ensembl.
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   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR012777; Leukotriene_A4_hydrolase.
DR   InterPro; IPR001930; Peptidase_M1.
DR   InterPro; IPR015211; Peptidase_M1_C.
DR   InterPro; IPR014782; Peptidase_M1_N.
DR   PANTHER; PTHR11533; PTHR11533; 1.
DR   Pfam; PF09127; Leuk-A4-hydro_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   TIGRFAMs; TIGR02411; leuko_A4_hydro; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Complete proteome; Cytoplasm; Hydrolase;
KW   Leukotriene biosynthesis; Metal-binding; Metalloprotease;
KW   Phosphoprotein; Protease; Reference proteome; Zinc.
FT   INIT_MET      1      1       Removed. {ECO:0000250}.
FT   CHAIN         2    611       Leukotriene A-4 hydrolase.
FT                                /FTId=PRO_0000095125.
FT   REGION      135    137       Substrate binding. {ECO:0000250}.
FT   REGION      267    272       Substrate binding. {ECO:0000250}.
FT   REGION      564    566       Substrate binding. {ECO:0000250}.
FT   ACT_SITE    297    297       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10095}.
FT   ACT_SITE    384    384       Proton donor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10095}.
FT   METAL       296    296       Zinc; catalytic.
FT   METAL       300    300       Zinc; catalytic.
FT   METAL       319    319       Zinc; catalytic.
FT   SITE        376    376       Essential for epoxide hydrolase activity,
FT                                but not for aminopeptidase activity.
FT                                {ECO:0000250}.
FT   SITE        379    379       Covalently modified during suicide
FT                                inhibition by leukotrienes.
FT                                {ECO:0000250}.
FT   MOD_RES      73     73       N6-acetyllysine. {ECO:0000250}.
FT   MOD_RES     337    337       N6-acetyllysine. {ECO:0000250}.
FT   MOD_RES     414    414       N6-acetyllysine. {ECO:0000250}.
FT   MOD_RES     416    416       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     573    573       N6-acetyllysine. {ECO:0000250}.
FT   MUTAGEN     296    296       H->Y: Complete loss of activity.
FT                                {ECO:0000269|PubMed:1881903}.
FT   MUTAGEN     300    300       H->Y: Complete loss of activity.
FT                                {ECO:0000269|PubMed:1881903}.
FT   MUTAGEN     319    319       E->Q: Complete loss of activity.
FT                                {ECO:0000269|PubMed:1881903}.
FT   MUTAGEN     384    384       Y->F,H,Q: Alters leukotriene hydrolase
FT                                activity, strongly enhancing the
FT                                formation of a metabolite that is
FT                                normally produced in trace amounts.
FT                                {ECO:0000269|PubMed:9287304}.
FT   CONFLICT    447    447       T -> A (in Ref. 1; AAB59675 and 3;
FT                                AAH21417). {ECO:0000305}.
SQ   SEQUENCE   611 AA;  69051 MW;  CCF8D30F6FA9721E CRC64;
     MPEVADTCSL ASPASVCRTQ HLHLRCSVDF ARRTLTGTAA LTVQSQEENL RSLTLDTKDL
     TIEKVVINGQ EVKYTLGESQ GYKGSPMEIS LPIALSKNQE IVIEISFETS PKSSALQWLT
     PEQTSGKQHP YLFSQCQAIH CRAILPCQDT PSVKLTYTAE VSVPKELVAL MSAIRDGEAP
     DPEDPSRKIY RFNQRVPIPC YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SANEFSETES
     MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH
     SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FHALGGWGEL QNTIKTFGES
     HPFTKLVVDL KDVDPDVAYS SIPYEKGFAL LFYLEQLLGG PEVFLGFLKA YVKKFSYQSV
     TTDDWKSFLY SHFKDKVDLL NQVDWNTWLY APGLPPVKPN YDVTLTNACI ALSQRWVTAK
     EEDLSSFSIA DLKDLSSHQL NEFLAQVLQK APLPLGHIKR MQEVYNFNAI NNSEIRFRWL
     RLCIQSKWEE AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVHTYQ EHKASMHPVT
     AMLVGRDLKV D
//
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