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Showing Protein Leukotriene A-4 hydrolase (HMDBP01015)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 6 metabolites
Identification
HMDB Protein ID HMDBP01015
Secondary Accession Numbers
  • 6303
  • HMDBP03701
Name Leukotriene A-4 hydrolase
Synonyms
  1. LTA-4 hydrolase
  2. Leukotriene A(4) hydrolase
Gene Name LTA4H
Protein Type Unknown
Biological Properties
General Function Involved in binding
Specific Function Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
Pathways
  • Acetaminophen Action Pathway
  • Acetylsalicylic Acid Action Pathway
  • Antipyrine Action Pathway
  • Antrafenine Action Pathway
  • Arachidonic acid metabolism
  • Arachidonic Acid Metabolism
  • Bromfenac Action Pathway
  • Carprofen Action Pathway
  • Celecoxib Action Pathway
  • Diclofenac Action Pathway
  • Diflunisal Action Pathway
  • Etodolac Action Pathway
  • Etoricoxib Action Pathway
  • Fenoprofen Action Pathway
  • Flurbiprofen Action Pathway
  • Ibuprofen Action Pathway
  • Indomethacin Action Pathway
  • Ketoprofen Action Pathway
  • Ketorolac Action Pathway
  • leukotriene B4 biosynthesis
  • Leukotriene C4 Synthesis Deficiency
  • Lornoxicam Action Pathway
  • Lumiracoxib Action Pathway
  • Magnesium salicylate Action Pathway
  • Mefenamic Acid Action Pathway
  • Meloxicam Action Pathway
  • Nabumetone Action Pathway
  • Naproxen Action Pathway
  • Nepafenac Action Pathway
  • Oxaprozin Action Pathway
  • Phenylbutazone Action Pathway
  • Piroxicam Action Pathway
  • Rofecoxib Action Pathway
  • Salicylate-sodium Action Pathway
  • Salicylic Acid Action Pathway
  • Salsalate Action Pathway
  • Sulindac Action Pathway
  • Suprofen Action Pathway
  • Tenoxicam Action Pathway
  • Tiaprofenic Acid Action Pathway
  • Tolmetin Action Pathway
  • Trisalicylate-choline Action Pathway
  • Valdecoxib Action Pathway
Reactions
Leukotriene A4 + Water → Leukotriene B4 details
GO Classification
Biological Process
response to zinc ion
inflammatory response
peptide catabolic process
Type I pneumocyte differentiation
response to peptide hormone stimulus
proteolysis
leukotriene biosynthetic process
Cellular Component
cytosol
nucleus
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
transition metal ion binding
zinc ion binding
hydrolase activity, acting on ether bonds
ether hydrolase activity
leukotriene-a4 hydrolase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
metallopeptidase activity
Molecular Function
metal ion binding
epoxide hydrolase activity
leukotriene-A4 hydrolase activity
aminopeptidase activity
metalloendopeptidase activity
zinc ion binding
Process
metabolic process
macromolecule metabolic process
cellular metabolic process
organic acid metabolic process
oxoacid metabolic process
carboxylic acid metabolic process
monocarboxylic acid metabolic process
fatty acid metabolic process
leukotriene biosynthetic process
protein metabolic process
proteolysis
unsaturated fatty acid metabolic process
icosanoid metabolic process
leukotriene metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 12
Locus 12q22
SNPs LTA4H
Gene Sequence 
>1836 bp
ATGCCCGAGATAGTGGATACCTGTTCGTTGGCCTCTCCGGCTTCCGTCTGCCGGACCAAG
CACCTGCACCTGCGCTGCAGCGTCGACTTTACTCGCCGGACGCTGACCGGGACTGCTGCT
CTCACGGTCCAGTCTCAGGAGGACAATCTGCGCAGCCTGGTTTTGGATACAAAGGACCTT
ACAATAGAAAAAGTAGTGATCAATGGACAAGAAGTCAAATATGCTCTTGGAGAAAGACAA
AGTTACAAGGGATCGCCAATGGAAATCTCTCTTCCTATCGCTTTGAGCAAAAATCAAGAA
ATTGTTATAGAAATTTCTTTTGAGACCTCTCCAAAATCTTCTGCTCTCCAGTGGCTCACT
CCTGAACAGACTTCTGGGAAGGAACACCCATATCTCTTTAGTCAGTGCCAGGCCATCCAC
TGCAGAGCAATCCTTCCTTGTCAGGACACTCCTTCTGTGAAATTAACCTATACTGCAGAG
GTGTCTGTCCCTAAAGAACTGGTGGCACTTATGAGTGCTATTCGTGATGGAGAAACACCT
GACCCAGAAGACCCAAGCAGGAAAATATACAAATTCATCCAAAAAGTTCCAATACCCTGC
TACCTGATTGCTTTAGTTGTTGGAGCTTTAGAAAGCAGGCAAATTGGCCCAAGAACTTTG
GTGTGGTCTGAGAAAGAGCAGGTGGAAAAGTCTGCTTATGAGTTTTCTGAGACTGAATCT
ATGCTTAAAATAGCAGAAGATCTGGGAGGACCGTATGTATGGGGACAGTATGACCTATTG
GTCCTGCCACCATCCTTCCCTTATGGTGGCATGGAGAATCCTTGCCTTACTTTTGTAACT
CCTACTCTACTGGCAGGCGACAAGTCACTCTCCAATGTCATTGCACATGAAATATCTCAT
AGCTGGACAGGGAATCTAGTGACCAACAAAACTTGGGATCACTTTTGGTTAAATGAGGGA
CATACTGTGTACTTGGAACGCCACATTTGCGGACGATTGTTTGGTGAAAAGTTCAGACAT
TTTAATGCTCTGGGAGGATGGGGAGAACTACAGAATTCGGTAAAGACATTTGGGGAGACA
CATCCTTTCACCAAACTTGTGGTTGATCTGACAGATATAGACCCTGATGTAGCTTATTCT
TCAGTTCCCTATGAGAAGGGCTTTGCTTTACTTTTTTACCTTGAACAACTGCTTGGAGGA
CCAGAGATTTTCCTAGGATTCTTAAAAGCTTATGTTGAGAAGTTTTCCTATAAGAGCATA
ACTACTGATGACTGGAAGGATTTCCTGTATTCCTATTTTAAAGATAAGGTTGATGTTCTC
AATCAAGTTGATTGGAATGCCTGGCTCTACTCTCCTGGACTGCCTCCCATAAAGCCCAAT
TATGATATGACTCTGACAAATGCTTGTATTGCCTTAAGTCAAAGATGGATTACTGCCAAA
GAAGATGATTTAAATTCATTCAATGCCACAGACCTGAAGGATCTCTCTTCTCATCAATTG
AATGAGTTTTTAGCACAGACGCTCCAGAGGGCACCTCTTCCATTGGGGCACATAAAGCGA
ATGCAAGAGGTGTACAACTTCAATGCCATTAACAATTCTGAAATACGATTCAGATGGCTG
CGGCTCTGCATTCAATCCAAGTGGGAGGACGCAATTCCTTTGGCGCTAAAGATGGCAACT
GAACAAGGAAGAATGAAGTTTACCCGGCCCTTATTCAAGGATCTTGCTGCCTTTGACAAA
TCCCATGATCAAGCTGTCCGAACCTACCAAGAGCACAAAGCAAGCATGCATCCCGTGACT
GCAATGCTGGTGGGGAAAGACTTAAAAGTGGATTAA
Protein Properties
Number of Residues 611
Molecular Weight 69284.64
Theoretical pI 6.177
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence 
>Leukotriene A-4 hydrolase
MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDL
TIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLT
PEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETP
DPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETES
MLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISH
SWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGET
HPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSI
TTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAK
EDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWL
RLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVT
AMLVGKDLKVD
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P09960
UniProtKB/Swiss-Prot Entry Name LKHA4_HUMAN
PDB IDs
GenBank Gene ID J03459
GeneCard ID LTA4H
GenAtlas ID LTA4H
HGNC ID HGNC:6710
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H, Shimizu T, Seyama Y, Suzuki K: Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis. J Biol Chem. 1987 Oct 15;262(29):13873-6. [PubMed:3654641 ]
  4. Funk CD, Radmark O, Fu JY, Matsumoto T, Jornvall H, Shimizu T, Samuelsson B: Molecular cloning and amino acid sequence of leukotriene A4 hydrolase. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6677-81. [PubMed:2821541 ]
  5. Mancini JA, Evans JF: Cloning and characterization of the human leukotriene A4 hydrolase gene. Eur J Biochem. 1995 Jul 1;231(1):65-71. [PubMed:7628486 ]
  6. Odlander B, Claesson HE, Bergman T, Radmark O, Jornvall H, Haeggstrom JZ: Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme. Arch Biochem Biophys. 1991 May 15;287(1):167-74. [PubMed:1897988 ]
  7. Radmark O, Shimizu T, Jornvall H, Samuelsson B: Leukotriene A4 hydrolase in human leukocytes. Purification and properties. J Biol Chem. 1984 Oct 25;259(20):12339-45. [PubMed:6490615 ]
  8. Jendraschak E, Kaminski WE, Kiefl R, von Schacky C: The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms. Biochem J. 1996 Mar 15;314 ( Pt 3):733-7. [PubMed:8615763 ]
  9. Toh H, Minami M, Shimizu T: Molecular evolution and zinc ion binding motif of leukotriene A4 hydrolase. Biochem Biophys Res Commun. 1990 Aug 31;171(1):216-21. [PubMed:1975494 ]
  10. Haeggstrom JZ, Wetterholm A, Shapiro R, Vallee BL, Samuelsson B: Leukotriene A4 hydrolase: a zinc metalloenzyme. Biochem Biophys Res Commun. 1990 Nov 15;172(3):965-70. [PubMed:2244921 ]
  11. Medina JF, Wetterholm A, Radmark O, Shapiro R, Haeggstrom JZ, Vallee BL, Samuelsson B: Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site-directed mutagenesis and zinc analysis. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7620-4. [PubMed:1881903 ]
  12. Minami M, Bito H, Ohishi N, Tsuge H, Miyano M, Mori M, Wada H, Mutoh H, Shimada S, Izumi T, et al.: Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297. FEBS Lett. 1992 Sep 14;309(3):353-7. [PubMed:1516710 ]
  13. Wetterholm A, Medina JF, Radmark O, Shapiro R, Haeggstrom JZ, Vallee BL, Samuelsson B: Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of glutamic acid-296. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9141-5. [PubMed:1357660 ]
  14. Thunnissen MM, Nordlund P, Haeggstrom JZ: Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol. 2001 Feb;8(2):131-5. [PubMed:11175901 ]
  15. Rudberg PC, Tholander F, Thunnissen MM, Haeggstrom JZ: Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms. J Biol Chem. 2002 Jan 11;277(2):1398-404. Epub 2001 Oct 23. [PubMed:11675384 ]