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 27-MAR-2024, entry version 252. 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 GLY-269; HIS-296; HIS-300 AND RP 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 --------------------------------------------------------------------------- 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; 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. 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 PDB; 7KZE; X-ray; 2.90 A; A/B/C=4-611. DR PDB; 7LLQ; X-ray; 2.85 A; A/B/C=1-611. DR PDB; 8AVA; X-ray; 1.35 A; A=2-611. DR PDB; 8AWH; X-ray; 1.42 A; A=2-611. DR PDB; 8QOW; X-ray; 2.35 A; A=2-611. DR PDB; 8QPN; X-ray; 2.00 A; A=2-611. DR PDB; 8QQ4; X-ray; 1.60 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 PDBsum; 7KZE; -. DR PDBsum; 7LLQ; -. DR PDBsum; 8AVA; -. DR PDBsum; 8AWH; -. DR PDBsum; 8QOW; -. DR PDBsum; 8QPN; -. DR PDBsum; 8QQ4; -. DR AlphaFoldDB; P09960; -. DR SMR; P09960; -. DR BioGRID; 110226; 55. DR IntAct; P09960; 13. 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 GlyCosmos; P09960; 2 sites, 1 glycan. 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; 9606-ENSP00000228740; -. 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 Pumba; P09960; -. DR Antibodypedia; 4453; 655 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 AGR; HGNC:6710; -. 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; CTALQWM; -. DR OrthoDB; 443480at2759; -. DR PhylomeDB; P09960; -. DR TreeFam; TF300758; -. DR BioCyc; MetaCyc:HS03372-MONOMER; -. 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; 9 hits in 1164 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 208 other cell types or tissues. DR ExpressionAtlas; P09960; baseline and differential. 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; 3.30.2010.30; -; 1. DR Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1. DR Gene3D; 1.25.40.320; Peptidase M1, leukotriene A4 hydrolase/aminopeptidase C-terminal domain; 1. DR Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 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 NCBIfam; TIGR02411; leuko_A4_hydro; 1. DR PANTHER; PTHR45726; LEUKOTRIENE A-4 HYDROLASE; 1. DR PANTHER; PTHR45726:SF3; LEUKOTRIENE A-4 HYDROLASE; 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; ARM repeat; 1. DR SUPFAM; SSF63737; Leukotriene A4 hydrolase N-terminal domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P09960; HS. 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="a peptide" FT /ligand_id="ChEBI:CHEBI:60466" FT /evidence="ECO:0000269|PubMed:18804029" FT BINDING 267..272 FT /ligand="a peptide" FT /ligand_id="ChEBI:CHEBI:60466" 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="a peptide" FT /ligand_id="ChEBI:CHEBI:60466" 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 //