LKHA4_HUMAN
ID LKHA4_HUMAN Reviewed; 611 AA.
AC P09960; B4DNQ9; F8VV40; Q6IAT6; Q9UCT7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 243.
DE RecName: Full=Leukotriene A-4 hydrolase;
DE Short=LTA-4 hydrolase;
DE EC=3.3.2.6 {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1881903, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:6490615, ECO:0000269|PubMed:7667299};
DE AltName: Full=Leukotriene A(4) hydrolase;
DE AltName: Full=Tripeptide aminopeptidase LTA4H {ECO:0000305};
DE EC=3.4.11.4 {ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:9395533};
GN Name=LTA4H; Synonyms=LTA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3654641; DOI=10.1016/s0021-9258(18)47872-6;
RA Minami M., Ohno S., Kawasaki H., Raedmark O., Samuelsson B., Joernvall H.,
RA Shimizu T., Seyama Y., Suzuki K.;
RT "Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase.
RT Complete primary structure of an enzyme involved in eicosanoid synthesis.";
RL J. Biol. Chem. 262:13873-13876(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2821541; DOI=10.1073/pnas.84.19.6677;
RA Funk C.D., Raadmark O., Fu J.Y., Matsumoto T., Joernvall H., Shimizu T.,
RA Samuelsson B.;
RT "Molecular cloning and amino acid sequence of leukotriene A4 hydrolase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6677-6681(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7628486; DOI=10.1111/j.1432-1033.1995.tb20671.x;
RA Mancini J.A., Evans J.F.;
RT "Cloning and characterization of the human leukotriene A4 hydrolase gene.";
RL Eur. J. Biochem. 231:65-71(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Esophageal carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-22, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=B-cell;
RX PubMed=1897988; DOI=10.1016/0003-9861(91)90402-5;
RA Odlander B., Claesson H.E., Bergman T., Radmark O., Joernvall H.,
RA Haeggstrom J.Z.;
RT "Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji:
RT indications of catalytically divergent forms of the enzyme.";
RL Arch. Biochem. Biophys. 287:167-174(1991).
RN [11]
RP PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RX PubMed=6490615; DOI=10.1016/s0021-9258(18)90750-7;
RA Radmark O., Shimizu T., Joernvall H., Samuelsson B.;
RT "Leukotriene A4 hydrolase in human leukocytes. Purification and
RT properties.";
RL J. Biol. Chem. 259:12339-12345(1984).
RN [12]
RP PROTEIN SEQUENCE OF 366-386, ACTIVITY REGULATION, COVALENT MODIFICATION AT
RP TYR-379, AND CATALYTIC ACTIVITY.
RX PubMed=7667299; DOI=10.1073/pnas.92.18.8383;
RA Mueller M.J., Wetterholm A., Blomster M., Jornvall H., Samuelsson B.,
RA Haeggstrom J.Z.;
RT "Leukotriene A4 hydrolase: mapping of a henicosapeptide involved in
RT mechanism-based inactivation.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8383-8387(1995).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 511-611, AND ALTERNATIVE SPLICING
RP (ISOFORMS 1 AND 2).
RX PubMed=8615763; DOI=10.1042/bj3140733;
RA Jendraschak E., Kaminski W.E., Kiefl R., von Schacky C.;
RT "The human leukotriene A4 hydrolase gene is expressed in two alternatively
RT spliced mRNA forms.";
RL Biochem. J. 314:733-737(1996).
RN [14]
RP ZINC-BINDING, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1975494; DOI=10.1016/0006-291x(90)91379-7;
RA Toh H., Minami M., Shimizu T.;
RT "Molecular evolution and zinc ion binding motif of leukotriene A4
RT hydrolase.";
RL Biochem. Biophys. Res. Commun. 171:216-221(1990).
RN [15]
RP ZINC-BINDING, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2244921; DOI=10.1016/0006-291x(90)91540-9;
RA Haeggstroem J.Z., Wetterholm A., Shapiro R., Vallee B.L., Samuelsson B.;
RT "Leukotriene A4 hydrolase: a zinc metalloenzyme.";
RL Biochem. Biophys. Res. Commun. 172:965-970(1990).
RN [16]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-296; HIS-300 AND GLU-319.
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 ligands
RT by site-directed mutagenesis and zinc analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7620-7624(1991).
RN [17]
RP MUTAGENESIS OF GLU-297.
RX PubMed=1516710; DOI=10.1016/0014-5793(92)80806-r;
RA Minami M., Bito H., Ohishi N., Tsuge H., Miyano M., Mori M., Wada H.,
RA Mutoh H., Shimada S., Izumi T., Abe K., Shimuzu T.;
RT "Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of
RT leukotriene A4 hydrolase and aminopeptidase activities by site-directed
RT mutagenesis at Glu-297.";
RL FEBS Lett. 309:353-357(1992).
RN [18]
RP MUTAGENESIS OF GLU-297.
RX PubMed=1357660; DOI=10.1073/pnas.89.19.9141;
RA Wetterholm A., Medina J.F., Raadmark O., Shapiro R., Haeggstroem J.Z.,
RA Vallee B.L., Samuelsson B.;
RT "Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation
RT of glutamic acid-296.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9141-9145(1992).
RN [19]
RP PHOSPHORYLATION AT SER-416, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=9395533; DOI=10.1074/jbc.272.50.31865;
RA Rybina I.V., Liu H., Gor Y., Feinmark S.J.;
RT "Regulation of leukotriene A4 hydrolase activity in endothelial cells by
RT phosphorylation.";
RL J. Biol. Chem. 272:31865-31871(1997).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-337; LYS-414 AND LYS-573,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20813919; DOI=10.1126/science.1190594;
RA Snelgrove R.J., Jackson P.L., Hardison M.T., Noerager B.D., Kinloch A.,
RA Gaggar A., Shastry S., Rowe S.M., Shim Y.M., Hussell T., Blalock J.E.;
RT "A critical role for LTA4H in limiting chronic pulmonary neutrophilic
RT inflammation.";
RL Science 330:90-94(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=21206090; DOI=10.1172/jci42545;
RA Oh S.F., Pillai P.S., Recchiuti A., Yang R., Serhan C.N.;
RT "Pro-resolving actions and stereoselective biosynthesis of 18S E-series
RT resolvins in human leukocytes and murine inflammation.";
RL J. Clin. Invest. 121:569-581(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH ZINC AND BESTATIN.
RX PubMed=11175901; DOI=10.1038/84117;
RA Thunnissen M.M.G.M., Nordlund P., Haeggstroem J.Z.;
RT "Crystal structure of human leukotriene A(4) hydrolase, a bifunctional
RT enzyme in inflammation.";
RL Nat. Struct. Biol. 8:131-135(2001).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH CAPTOPRIL AND ZINC
RP IONS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, AND ACTIVE SITE.
RX PubMed=12207002; DOI=10.1096/fj.01-1017fje;
RA Thunnissen M.M., Andersson B., Samuelsson B., Wong C.H., Haeggstrom J.Z.;
RT "Crystal structures of leukotriene A4 hydrolase in complex with captopril
RT and two competitive tight-binding inhibitors.";
RL FASEB J. 16:1648-1650(2002).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2-611 IN COMPLEX WITH ZINC, ACTIVE
RP SITE, MUTAGENESIS OF GLN-137; GLY-270; MET-271; GLU-272 AND ASN-273,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11675384; DOI=10.1074/jbc.m106577200;
RA Rudberg P.C., Tholander F., Thunnissen M.M.G.M., Haeggstroem J.Z.;
RT "Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic
RT residue with specific roles in two distinct enzyme mechanisms.";
RL J. Biol. Chem. 277:1398-1404(2002).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ASN-376 IN COMPLEX WITH
RP BESTATIN AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP GLN-135; HIS-140; ASP-372; ASP-374; ASP-376 AND GLU-385.
RX PubMed=11917124; DOI=10.1073/pnas.072090099;
RA Rudberg P.C., Tholander F., Thunnissen M.M., Samuelsson B.,
RA Haeggstrom J.Z.;
RT "Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation
RT by mutation of aspartic acid 375.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4215-4220(2002).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ALA-564 IN COMPLEX WITH
RP ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, AND MUTAGENESIS OF
RP ARG-564 AND LYS-566.
RX PubMed=15078870; DOI=10.1074/jbc.m401031200;
RA Rudberg P.C., Tholander F., Andberg M., Thunnissen M.M., Haeggstrom J.Z.;
RT "Leukotriene A4 hydrolase: identification of a common carboxylate
RT recognition site for the epoxide hydrolase and aminopeptidase substrates.";
RL J. Biol. Chem. 279:27376-27382(2004).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF MUTANT GLN-297 IN COMPLEXES WITH
RP SUBSTRATE TRIPEPTIDES AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION,
RP COFACTOR, AND MUTAGENESIS OF GLU-297 AND ASP-376.
RX PubMed=18804029; DOI=10.1016/j.chembiol.2008.07.018;
RA Tholander F., Muroya A., Roques B.P., Fournie-Zaluski M.C.,
RA Thunnissen M.M., Haeggstrom J.Z.;
RT "Structure-based dissection of the active site chemistry of leukotriene A4
RT hydrolase: implications for M1 aminopeptidases and inhibitor design.";
RL Chem. Biol. 15:920-929(2008).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) IN COMPLEXES WITH INHIBITORS AND
RP ZINC IONS.
RX PubMed=19618939; DOI=10.1021/jm900259h;
RA Davies D.R., Mamat B., Magnusson O.T., Christensen J., Haraldsson M.H.,
RA Mishra R., Pease B., Hansen E., Singh J., Zembower D., Kim H.,
RA Kiselyov A.S., Burgin A.B., Gurney M.E., Stewart L.J.;
RT "Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased
RT fragment crystallography.";
RL J. Med. Chem. 52:4694-4715(2009).
RN [34] {ECO:0007744|PDB:4L2L, ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6}
RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) IN COMPLEX WITH PRO-GLY-PRO ANALOG
RP 4-(4-BENZYLPHENYL)THIAZOL-2-AMINE AND ZINC IONS, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RX PubMed=24591641; DOI=10.1073/pnas.1402136111;
RA Stsiapanava A., Olsson U., Wan M., Kleinschmidt T., Rutishauser D.,
RA Zubarev R.A., Samuelsson B., Rinaldo-Matthis A., Haeggstrom J.Z.;
RT "Binding of Pro-Gly-Pro at the active site of leukotriene A4
RT hydrolase/aminopeptidase and development of an epoxide hydrolase selective
RT inhibitor.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:4227-4232(2014).
CC -!- FUNCTION: Bifunctional zinc metalloenzyme that comprises both epoxide
CC hydrolase (EH) and aminopeptidase activities. Acts as an epoxide
CC hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory
CC mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002,
CC PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494,
CC PubMed:2244921). Has also aminopeptidase activity, with high affinity
CC for N-terminal arginines of various synthetic tripeptides
CC (PubMed:20813919, PubMed:18804029). In addition to its pro-inflammatory
CC EH activity, may also counteract inflammation by its aminopeptidase
CC activity, which inactivates by cleavage another neutrophil attractant,
CC the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen
CC generated by the action of matrix metalloproteinase-9 (MMP9) and
CC prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641).
CC Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1
CC from eicosapentaenoic acid, two lipid mediators that show potent anti-
CC inflammatory and pro-resolving actions (PubMed:21206090).
CC {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002,
CC ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029,
CC ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494,
CC ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090,
CC ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641}.
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 Evidence={ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124,
CC ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870,
CC ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988,
CC ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:6490615,
CC ECO:0000269|PubMed:7667299, ECO:0000269|PubMed:9395533};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22325;
CC Evidence={ECO:0000305|PubMed:11917124};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-
CC eicosapentaenoate + H2O = resolvin E1; Xref=Rhea:RHEA:50272,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:91000, ChEBI:CHEBI:132219;
CC Evidence={ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50273;
CC Evidence={ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-
CC eicosapentaenoate + H2O = 18S-resolvin E1; Xref=Rhea:RHEA:51988,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:134661, ChEBI:CHEBI:136057;
CC Evidence={ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51989;
CC Evidence={ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of the N-terminal residue from a tripeptide.;
CC EC=3.4.11.4; Evidence={ECO:0000269|PubMed:11675384,
CC ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:20813919,
CC ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:9395533};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:12207002,
CC ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029,
CC ECO:0000269|PubMed:24591641};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12207002,
CC ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029};
CC -!- ACTIVITY REGULATION: Inhibited by bestatin (PubMed:11175901). The
CC epoxide hydrolase activity is restrained by suicide inactivation that
CC involves binding of LTA4 to Tyr-379 (PubMed:7667299). 4-(4-
CC benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide
CC hydrolase activity (PubMed:24591641). {ECO:0000269|PubMed:11175901,
CC ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:7667299}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.29 mM for Pro-Gly-Pro {ECO:0000269|PubMed:20813919};
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis.
CC {ECO:0000269|PubMed:11917124}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11917124,
CC ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870}.
CC -!- INTERACTION:
CC P09960; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-721089, EBI-717399;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:6490615}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=L-LTA4;
CC IsoId=P09960-1; Sequence=Displayed;
CC Name=2; Synonyms=S-LTA4;
CC IsoId=P09960-2; Sequence=VSP_041108, VSP_041109;
CC Name=3;
CC IsoId=P09960-3; Sequence=VSP_041107, VSP_041108, VSP_041109;
CC Name=4;
CC IsoId=P09960-4; Sequence=VSP_041107;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in monocytes,
CC lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.
CC -!- PTM: Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase
CC activity. {ECO:0000269|PubMed:9395533}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; J03459; AAA36176.1; -; mRNA.
DR EMBL; J02959; AAA36177.1; -; mRNA.
DR EMBL; U27293; AAA89077.1; -; Genomic_DNA.
DR EMBL; U27275; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27276; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27277; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27278; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27279; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27280; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27281; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27282; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27283; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27284; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27285; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27286; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27287; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27288; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27289; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27290; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27291; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; U27292; AAA89077.1; JOINED; Genomic_DNA.
DR EMBL; AK298017; BAG60321.1; -; mRNA.
DR EMBL; CR457068; CAG33349.1; -; mRNA.
DR EMBL; BX647158; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC007298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97559.1; -; Genomic_DNA.
DR EMBL; BC032528; AAH32528.1; -; mRNA.
DR EMBL; U43410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U43411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS58266.1; -. [P09960-3]
DR CCDS; CCDS58267.1; -. [P09960-4]
DR CCDS; CCDS9059.1; -. [P09960-1]
DR PIR; S65947; S65947.
DR RefSeq; NP_000886.1; NM_000895.2. [P09960-1]
DR RefSeq; NP_001243572.1; NM_001256643.1. [P09960-4]
DR RefSeq; NP_001243573.1; NM_001256644.1. [P09960-3]
DR RefSeq; XP_005268928.1; XM_005268871.1. [P09960-2]
DR PDB; 1GW6; X-ray; 2.20 A; A=2-611.
DR PDB; 1H19; X-ray; 2.10 A; A=2-611.
DR PDB; 1HS6; X-ray; 1.95 A; A=1-611.
DR PDB; 1SQM; X-ray; 2.30 A; A=2-611.
DR PDB; 2R59; X-ray; 1.89 A; A=2-611.
DR PDB; 2VJ8; X-ray; 1.80 A; A=1-611.
DR PDB; 3B7R; X-ray; 1.81 A; L=2-611.
DR PDB; 3B7S; X-ray; 1.47 A; A=2-611.
DR PDB; 3B7T; X-ray; 2.30 A; A=2-611.
DR PDB; 3B7U; X-ray; 1.90 A; X=2-611.
DR PDB; 3CHO; X-ray; 1.80 A; A=2-611.
DR PDB; 3CHP; X-ray; 2.10 A; A=2-611.
DR PDB; 3CHQ; X-ray; 2.09 A; A=2-611.
DR PDB; 3CHR; X-ray; 2.20 A; A=2-611.
DR PDB; 3CHS; X-ray; 2.55 A; A=2-611.
DR PDB; 3FH5; X-ray; 1.63 A; A=1-611.
DR PDB; 3FH7; X-ray; 2.05 A; A=1-611.
DR PDB; 3FH8; X-ray; 1.67 A; A=1-611.
DR PDB; 3FHE; X-ray; 2.16 A; A=1-611.
DR PDB; 3FTS; X-ray; 2.33 A; A=1-611.
DR PDB; 3FTU; X-ray; 1.90 A; A=1-611.
DR PDB; 3FTV; X-ray; 1.70 A; A=1-611.
DR PDB; 3FTW; X-ray; 1.85 A; A=1-611.
DR PDB; 3FTX; X-ray; 1.96 A; A=1-611.
DR PDB; 3FTY; X-ray; 2.15 A; A=1-611.
DR PDB; 3FTZ; X-ray; 2.00 A; A=1-611.
DR PDB; 3FU0; X-ray; 1.80 A; A=1-611.
DR PDB; 3FU3; X-ray; 2.00 A; A=1-611.
DR PDB; 3FU5; X-ray; 2.30 A; A=1-611.
DR PDB; 3FU6; X-ray; 2.05 A; A=1-611.
DR PDB; 3FUD; X-ray; 2.20 A; A=1-611.
DR PDB; 3FUE; X-ray; 2.38 A; A=1-611.
DR PDB; 3FUF; X-ray; 2.60 A; A=1-611.
DR PDB; 3FUH; X-ray; 1.80 A; A=1-611.
DR PDB; 3FUI; X-ray; 2.20 A; A=1-611.
DR PDB; 3FUJ; X-ray; 1.90 A; A=1-611.
DR PDB; 3FUK; X-ray; 1.95 A; A=1-611.
DR PDB; 3FUL; X-ray; 2.39 A; A=1-611.
DR PDB; 3FUM; X-ray; 2.15 A; A=1-611.
DR PDB; 3FUN; X-ray; 1.58 A; A=1-611.
DR PDB; 3U9W; X-ray; 1.25 A; A=4-611.
DR PDB; 4DPR; X-ray; 2.02 A; A=1-611.
DR PDB; 4L2L; X-ray; 1.65 A; A=1-611.
DR PDB; 4MKT; X-ray; 1.62 A; A=1-611.
DR PDB; 4MS6; X-ray; 1.72 A; A=1-611.
DR PDB; 4R7L; X-ray; 1.66 A; A=1-611.
DR PDB; 4RSY; X-ray; 1.93 A; A=1-611.
DR PDB; 4RVB; X-ray; 1.93 A; A=1-611.
DR PDB; 5AEN; X-ray; 1.86 A; A=4-611.
DR PDB; 5BPP; X-ray; 2.03 A; A=1-611.
DR PDB; 5FWQ; X-ray; 2.05 A; A=1-611.
DR PDB; 5N3W; X-ray; 2.30 A; A=1-611.
DR PDB; 5NI2; X-ray; 1.50 A; A=2-611.
DR PDB; 5NI4; X-ray; 1.90 A; A/B/C=2-611.
DR PDB; 5NI6; X-ray; 1.54 A; A=2-611.
DR PDB; 5NIA; X-ray; 1.76 A; A=2-611.
DR PDB; 5NID; X-ray; 1.57 A; A=2-611.
DR PDB; 5NIE; X-ray; 2.60 A; A/B/C=2-611.
DR PDB; 6ENB; X-ray; 1.84 A; A=2-611.
DR PDB; 6ENC; X-ray; 1.95 A; A=2-611.
DR PDB; 6END; X-ray; 2.24 A; A=2-611.
DR PDB; 6O5H; X-ray; 2.84 A; A/B/C=4-611.
DR PDB; 7AUZ; X-ray; 1.90 A; A=2-611.
DR PDB; 7AV0; X-ray; 1.90 A; A=2-611.
DR PDB; 7AV1; X-ray; 1.79 A; A=2-611.
DR PDB; 7AV2; X-ray; 1.95 A; A=2-611.
DR PDBsum; 1GW6; -.
DR PDBsum; 1H19; -.
DR PDBsum; 1HS6; -.
DR PDBsum; 1SQM; -.
DR PDBsum; 2R59; -.
DR PDBsum; 2VJ8; -.
DR PDBsum; 3B7R; -.
DR PDBsum; 3B7S; -.
DR PDBsum; 3B7T; -.
DR PDBsum; 3B7U; -.
DR PDBsum; 3CHO; -.
DR PDBsum; 3CHP; -.
DR PDBsum; 3CHQ; -.
DR PDBsum; 3CHR; -.
DR PDBsum; 3CHS; -.
DR PDBsum; 3FH5; -.
DR PDBsum; 3FH7; -.
DR PDBsum; 3FH8; -.
DR PDBsum; 3FHE; -.
DR PDBsum; 3FTS; -.
DR PDBsum; 3FTU; -.
DR PDBsum; 3FTV; -.
DR PDBsum; 3FTW; -.
DR PDBsum; 3FTX; -.
DR PDBsum; 3FTY; -.
DR PDBsum; 3FTZ; -.
DR PDBsum; 3FU0; -.
DR PDBsum; 3FU3; -.
DR PDBsum; 3FU5; -.
DR PDBsum; 3FU6; -.
DR PDBsum; 3FUD; -.
DR PDBsum; 3FUE; -.
DR PDBsum; 3FUF; -.
DR PDBsum; 3FUH; -.
DR PDBsum; 3FUI; -.
DR PDBsum; 3FUJ; -.
DR PDBsum; 3FUK; -.
DR PDBsum; 3FUL; -.
DR PDBsum; 3FUM; -.
DR PDBsum; 3FUN; -.
DR PDBsum; 3U9W; -.
DR PDBsum; 4DPR; -.
DR PDBsum; 4L2L; -.
DR PDBsum; 4MKT; -.
DR PDBsum; 4MS6; -.
DR PDBsum; 4R7L; -.
DR PDBsum; 4RSY; -.
DR PDBsum; 4RVB; -.
DR PDBsum; 5AEN; -.
DR PDBsum; 5BPP; -.
DR PDBsum; 5FWQ; -.
DR PDBsum; 5N3W; -.
DR PDBsum; 5NI2; -.
DR PDBsum; 5NI4; -.
DR PDBsum; 5NI6; -.
DR PDBsum; 5NIA; -.
DR PDBsum; 5NID; -.
DR PDBsum; 5NIE; -.
DR PDBsum; 6ENB; -.
DR PDBsum; 6ENC; -.
DR PDBsum; 6END; -.
DR PDBsum; 6O5H; -.
DR PDBsum; 7AUZ; -.
DR PDBsum; 7AV0; -.
DR PDBsum; 7AV1; -.
DR PDBsum; 7AV2; -.
DR AlphaFoldDB; P09960; -.
DR SMR; P09960; -.
DR BioGRID; 110226; 43.
DR IntAct; P09960; 11.
DR MINT; P09960; -.
DR STRING; 9606.ENSP00000228740; -.
DR BindingDB; P09960; -.
DR ChEMBL; CHEMBL4618; -.
DR DrugBank; DB07102; (2S)-2-amino-5-oxo-5-[(4-phenylmethoxyphenyl)amino]pentanoic acid.
DR DrugBank; DB06917; (4-fluorophenyl)(pyridin-4-yl)methanone.
DR DrugBank; DB07258; (R)-pyridin-4-yl[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanol.
DR DrugBank; DB07094; 1-(2,2'-bithiophen-5-yl)methanamine.
DR DrugBank; DB07259; 1-(4-thiophen-2-ylphenyl)methanamine.
DR DrugBank; DB02352; 3-(Benzyloxy)Pyridin-2-Amine.
DR DrugBank; DB07292; 4-(2-amino-1,3-thiazol-4-yl)phenol.
DR DrugBank; DB07104; 4-amino-N-[4-(benzyloxy)phenyl]butanamide.
DR DrugBank; DB06828; 5-[2-(1H-pyrrol-1-yl)ethoxy]-1H-indole.
DR DrugBank; DB08466; 5-[2-(4-hydroxyphenyl)ethyl]benzene-1,3-diol.
DR DrugBank; DB01197; Captopril.
DR DrugBank; DB05177; DG051.
DR DrugBank; DB03366; Imidazole.
DR DrugBank; DB08040; Kelatorphan.
DR DrugBank; DB06851; N-(pyridin-3-ylmethyl)aniline.
DR DrugBank; DB02062; N-[3-[(1-Aminoethyl)(Hydroxy)Phosphoryl]-2-(1,1'-Biphenyl-4-Ylmethyl)Propanoyl]Alanine.
DR DrugBank; DB07099; N-[4-(benzyloxy)phenyl]glycinamide.
DR DrugBank; DB07260; N-benzyl-4-[(2R)-pyrrolidin-2-ylmethoxy]aniline.
DR DrugBank; DB07196; N-methyl-1-(2-thiophen-2-ylphenyl)methanamine.
DR DrugBank; DB11781; Tosedostat.
DR DrugBank; DB03424; Ubenimex.
DR DrugBank; DB07237; {4-[(2R)-pyrrolidin-2-ylmethoxy]phenyl}(4-thiophen-3-ylphenyl)methanone.
DR DrugCentral; P09960; -.
DR GuidetoPHARMACOLOGY; 1395; -.
DR SwissLipids; SLP:000001118; -.
DR MEROPS; M01.004; -.
DR MoonProt; P09960; -.
DR GlyGen; P09960; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P09960; -.
DR MetOSite; P09960; -.
DR PhosphoSitePlus; P09960; -.
DR SwissPalm; P09960; -.
DR BioMuta; LTA4H; -.
DR DMDM; 126353; -.
DR REPRODUCTION-2DPAGE; IPI00219077; -.
DR CPTAC; CPTAC-92; -.
DR CPTAC; CPTAC-93; -.
DR EPD; P09960; -.
DR jPOST; P09960; -.
DR MassIVE; P09960; -.
DR MaxQB; P09960; -.
DR PaxDb; P09960; -.
DR PeptideAtlas; P09960; -.
DR PRIDE; P09960; -.
DR ProteomicsDB; 28779; -.
DR ProteomicsDB; 52284; -. [P09960-1]
DR ProteomicsDB; 52285; -. [P09960-2]
DR ProteomicsDB; 52286; -. [P09960-3]
DR Antibodypedia; 4453; 553 antibodies from 37 providers.
DR DNASU; 4048; -.
DR Ensembl; ENST00000228740.7; ENSP00000228740.2; ENSG00000111144.10. [P09960-1]
DR Ensembl; ENST00000413268.6; ENSP00000395051.2; ENSG00000111144.10. [P09960-3]
DR Ensembl; ENST00000552789.5; ENSP00000449958.1; ENSG00000111144.10. [P09960-4]
DR GeneID; 4048; -.
DR KEGG; hsa:4048; -.
DR MANE-Select; ENST00000228740.7; ENSP00000228740.2; NM_000895.3; NP_000886.1.
DR UCSC; uc001ten.3; human. [P09960-1]
DR CTD; 4048; -.
DR DisGeNET; 4048; -.
DR GeneCards; LTA4H; -.
DR HGNC; HGNC:6710; LTA4H.
DR HPA; ENSG00000111144; Low tissue specificity.
DR MIM; 151570; gene.
DR neXtProt; NX_P09960; -.
DR OpenTargets; ENSG00000111144; -.
DR PharmGKB; PA24345; -.
DR VEuPathDB; HostDB:ENSG00000111144; -.
DR eggNOG; KOG1047; Eukaryota.
DR GeneTree; ENSGT00940000156375; -.
DR HOGENOM; CLU_014505_0_0_1; -.
DR InParanoid; P09960; -.
DR OMA; YHPICRQ; -.
DR PhylomeDB; P09960; -.
DR TreeFam; TF300758; -.
DR BioCyc; MetaCyc:HS03372-MON; -.
DR BRENDA; 3.3.2.6; 2681.
DR BRENDA; 3.4.11.6; 2681.
DR PathwayCommons; P09960; -.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9018676; Biosynthesis of D-series resolvins.
DR Reactome; R-HSA-9018681; Biosynthesis of protectins.
DR Reactome; R-HSA-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-HSA-9020265; Biosynthesis of aspirin-triggered D-series resolvins.
DR Reactome; R-HSA-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR SABIO-RK; P09960; -.
DR SignaLink; P09960; -.
DR UniPathway; UPA00878; -.
DR BioGRID-ORCS; 4048; 8 hits in 1083 CRISPR screens.
DR ChiTaRS; LTA4H; human.
DR EvolutionaryTrace; P09960; -.
DR GenomeRNAi; 4048; -.
DR Pharos; P09960; Tchem.
DR PRO; PR:P09960; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P09960; protein.
DR Bgee; ENSG00000111144; Expressed in monocyte and 206 other tissues.
DR ExpressionAtlas; P09960; baseline and differential.
DR Genevisible; P09960; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004301; F:epoxide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004463; F:leukotriene-A4 hydrolase activity; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IMP:CAFA.
DR GO; GO:0008233; F:peptidase activity; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0045148; F:tripeptide aminopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043171; P:peptide catabolic process; IDA:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; IMP:CAFA.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0060509; P:type I pneumocyte differentiation; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Leukotriene biosynthesis;
KW Lipid metabolism; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1897988,
FT ECO:0000269|PubMed:6490615, ECO:0007744|PubMed:22223895"
FT CHAIN 2..611
FT /note="Leukotriene A-4 hydrolase"
FT /id="PRO_0000095124"
FT ACT_SITE 297
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:11675384,
FT ECO:0000305|PubMed:12207002, ECO:0000305|PubMed:24591641,
FT ECO:0007744|PDB:1H19"
FT ACT_SITE 384
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:11675384,
FT ECO:0000305|PubMed:12207002, ECO:0000305|PubMed:24591641,
FT ECO:0007744|PDB:1H19"
FT BINDING 135..137
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18804029"
FT BINDING 267..272
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18804029"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11175901,
FT ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124,
FT ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870,
FT ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:19618939,
FT ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6,
FT ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6,
FT ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59,
FT ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R,
FT ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T,
FT ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO,
FT ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ,
FT ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS,
FT ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7,
FT ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE,
FT ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU,
FT ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW,
FT ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY,
FT ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0,
FT ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5,
FT ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD,
FT ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF,
FT ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI,
FT ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK,
FT ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM,
FT ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W,
FT ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L,
FT ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6,
FT ECO:0007744|PDB:5AEN"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11175901,
FT ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124,
FT ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870,
FT ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:19618939,
FT ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6,
FT ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6,
FT ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59,
FT ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R,
FT ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T,
FT ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO,
FT ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ,
FT ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS,
FT ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7,
FT ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE,
FT ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU,
FT ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW,
FT ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY,
FT ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0,
FT ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5,
FT ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD,
FT ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF,
FT ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI,
FT ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK,
FT ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM,
FT ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W,
FT ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L,
FT ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6,
FT ECO:0007744|PDB:5AEN"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11175901,
FT ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6,
FT ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6,
FT ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59,
FT ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R,
FT ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T,
FT ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO,
FT ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ,
FT ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS,
FT ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7,
FT ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE,
FT ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU,
FT ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW,
FT ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY,
FT ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0,
FT ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5,
FT ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD,
FT ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF,
FT ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI,
FT ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK,
FT ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM,
FT ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W,
FT ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L,
FT ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6,
FT ECO:0007744|PDB:5AEN"
FT BINDING 564..566
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18804029"
FT SITE 272
FT /note="Pro-Gly-Pro binding"
FT /evidence="ECO:0000269|PubMed:24591641"
FT SITE 376
FT /note="Essential for epoxide hydrolase activity, but not
FT for aminopeptidase activity"
FT /evidence="ECO:0000269|PubMed:11917124"
FT SITE 379
FT /note="Covalently modified during suicide inhibition by
FT leukotrienes"
FT /evidence="ECO:0000269|PubMed:7667299"
FT SITE 563
FT /note="Pro-Gly-Pro binding"
FT /evidence="ECO:0000269|PubMed:24591641"
FT MOD_RES 73
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 337
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 414
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9395533"
FT MOD_RES 573
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..53
FT /note="MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRS
FT L -> MLPQRNLSKRQVPTMHIPVKTRRLLAALK (in isoform 3 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_041107"
FT VAR_SEQ 511..532
FT /note="APLPLGHIKRMQEVYNFNAINN -> MAAALHSIQVGGRNSFGAKDGN (in
FT isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041108"
FT VAR_SEQ 533..611
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041109"
FT VARIANT 131
FT /note="Y -> H (in dbSNP:rs45630737)"
FT /id="VAR_051570"
FT MUTAGEN 135
FT /note="Q->A,L: Srongly increased epoxide hydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 135
FT /note="Q->A: Strongly reduced aminopeptidase activity.
FT Strongly decreased affinity for leukotriene. Abolishes
FT epoxide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 137
FT /note="Q->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 137
FT /note="Q->L: Aminopeptidase activity strongly impaired, but
FT keeps LTA4 activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 137
FT /note="Q->N: Aminopeptidase activity almost absent, but
FT keeps LTA4 activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 140
FT /note="H->Q: Aminopeptidase activity almost absent, but
FT keeps LTA4 activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 269
FT /note="G->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:1881903"
FT MUTAGEN 270
FT /note="G->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 271
FT /note="M->L: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 272
FT /note="E->A,D: Complete loss of epoxide hydrolase activity
FT and aminopeptidase activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 272
FT /note="E->Q: Loss of LTA4 hydrolase activity, and
FT aminopeptidase activity strongly impaired."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 273
FT /note="N->A: No loss of epoxide hydrolase activity and
FT aminopeptidase activity."
FT /evidence="ECO:0000269|PubMed:11675384"
FT MUTAGEN 296
FT /note="H->Y: Complete loss of LTA4 hydrolase and peptidase
FT enzyme activities."
FT /evidence="ECO:0000269|PubMed:1881903"
FT MUTAGEN 297
FT /note="E->A: Loss of epoxide hydrolase and aminopeptidase
FT activities."
FT /evidence="ECO:0000269|PubMed:1357660,
FT ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"
FT MUTAGEN 297
FT /note="E->K: Loss of epoxide hydrolase and aminopeptidase
FT activities."
FT /evidence="ECO:0000269|PubMed:1357660,
FT ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"
FT MUTAGEN 297
FT /note="E->Q: Loss of aminopeptidase activity, but keeps
FT LTA4 hydrolase activity."
FT /evidence="ECO:0000269|PubMed:1357660,
FT ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"
FT MUTAGEN 300
FT /note="H->L: Complete loss of LTA4 hydrolase and peptidase
FT enzyme activities."
FT /evidence="ECO:0000269|PubMed:1881903"
FT MUTAGEN 319
FT /note="E->A: Complete loss of LTA4 hydrolase and peptidase
FT enzyme activities."
FT /evidence="ECO:0000269|PubMed:1881903"
FT MUTAGEN 372
FT /note="D->N: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 374
FT /note="D->N: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 376
FT /note="D->A: Strongly reduced hydrolysis of peptides
FT starting with Arg. Small effect on hydrolysis of peptides
FT starting with Ala. Abolishes epoxide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:11917124,
FT ECO:0000269|PubMed:18804029"
FT MUTAGEN 376
FT /note="D->E: Strongly reduced aminopeptidase activity.
FT Abolishes epoxide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:11917124,
FT ECO:0000269|PubMed:18804029"
FT MUTAGEN 376
FT /note="D->N: Abolishes aminopeptidase activity. Decreased
FT epoxide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:11917124,
FT ECO:0000269|PubMed:18804029"
FT MUTAGEN 385
FT /note="E->Q: Reduced aminopeptidase activity. Minor effect
FT on epoxide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:11917124"
FT MUTAGEN 564
FT /note="R->A,K,M: Abolishes epoxide hydrolase activity.
FT Reduced aminopeptidase activity."
FT /evidence="ECO:0000269|PubMed:15078870"
FT MUTAGEN 566
FT /note="K->A,M: Strongly reduced affinity for peptide
FT substrates. Reduced epoxide hydrolase and aminopeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:15078870"
FT MUTAGEN 566
FT /note="K->R: No effect on epoxide hydrolase and
FT aminopeptidase activity."
FT /evidence="ECO:0000269|PubMed:15078870"
FT CONFLICT 115
FT /note="A -> T (in Ref. 6; BX647158)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="Q -> R (in Ref. 6; BX647158)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="E -> G (in Ref. 4; BAG60321)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="N -> S (in Ref. 6; BX647158)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="A -> V (in Ref. 6; BX647158)"
FT /evidence="ECO:0000305"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 17..29
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 30..33
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 34..45
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 50..59
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 85..95
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 100..108
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 155..164
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 167..180
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2VJ8"
FT STRAND 187..198
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 228..234
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 238..249
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:5NIE"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 292..299
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 315..334
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 336..357
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 382..398
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 401..415
FT /evidence="ECO:0007829|PDB:3U9W"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 422..432
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 437..441
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 445..450
FT /evidence="ECO:0007829|PDB:3U9W"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 467..478
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 481..486
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 497..508
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 515..525
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 533..545
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 551..561
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 565..577
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 579..592
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:3U9W"
FT HELIX 598..608
FT /evidence="ECO:0007829|PDB:3U9W"
SQ SEQUENCE 611 AA; 69285 MW; 329BF6D04D4A06E1 CRC64;
MPEIVDTCSL ASPASVCRTK HLHLRCSVDF TRRTLTGTAA LTVQSQEDNL RSLVLDTKDL
TIEKVVINGQ EVKYALGERQ SYKGSPMEIS LPIALSKNQE IVIEISFETS PKSSALQWLT
PEQTSGKEHP YLFSQCQAIH CRAILPCQDT PSVKLTYTAE VSVPKELVAL MSAIRDGETP
DPEDPSRKIY KFIQKVPIPC YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SAYEFSETES
MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH
SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FNALGGWGEL QNSVKTFGET
HPFTKLVVDL TDIDPDVAYS SVPYEKGFAL LFYLEQLLGG PEIFLGFLKA YVEKFSYKSI
TTDDWKDFLY SYFKDKVDVL NQVDWNAWLY SPGLPPIKPN YDMTLTNACI ALSQRWITAK
EDDLNSFNAT DLKDLSSHQL NEFLAQTLQR APLPLGHIKR MQEVYNFNAI NNSEIRFRWL
RLCIQSKWED AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVRTYQ EHKASMHPVT
AMLVGKDLKV D
