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P09960 (LKHA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukotriene A-4 hydrolase

Short name=LTA-4 hydrolase
EC=3.3.2.6
Alternative name(s):
Leukotriene A(4) hydrolase
Gene names
Name:LTA4H
Synonyms:LTA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length611 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity. Ref.10 Ref.14 Ref.15 Ref.24 Ref.26 Ref.27 Ref.28

Catalytic activity

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate. Ref.10 Ref.12 Ref.24 Ref.26 Ref.27 Ref.28

Cofactor

Binds 1 zinc ion per subunit. Ref.24 Ref.27 Ref.28

Enzyme regulation

Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4, due to the formation of a covalent adduct at Tyr-379. Ref.12

Pathway

Lipid metabolism; leukotriene B4 biosynthesis.

Subunit structure

Monomer.

Subcellular location

Cytoplasm.

Tissue specificity

Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.

Post-translational modification

Phosphorylation at Ser-416 inhibits enzymatic activity.

Sequence similarities

Belongs to the peptidase M1 family.

Ontologies

Keywords
   Biological processLeukotriene biosynthesis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Traceable author statement. Source: Reactome

inflammatory response

Non-traceable author statement Ref.23. Source: ProtInc

leukotriene biosynthetic process

Inferred from direct assay Ref.27. Source: UniProtKB

leukotriene metabolic process

Traceable author statement. Source: Reactome

peptide catabolic process

Inferred from direct assay Ref.27Ref.28. Source: UniProtKB

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionaminopeptidase activity

Inferred from direct assay Ref.27Ref.28. Source: UniProtKB

epoxide hydrolase activity

Inferred from direct assay Ref.27. Source: UniProtKB

leukotriene-A4 hydrolase activity

Inferred from direct assay Ref.27. Source: UniProtKB

metallopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activity

Traceable author statement Ref.16. Source: ProtInc

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.27Ref.28. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P09960-1)

Also known as: L-LTA4;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P09960-2)

Also known as: S-LTA4;

The sequence of this isoform differs from the canonical sequence as follows:
     511-532: APLPLGHIKRMQEVYNFNAINN → MAAALHSIQVGGRNSFGAKDGN
     533-611: Missing.
Isoform 3 (identifier: P09960-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MPEIVDTCSL...QSQEDNLRSL → MLPQRNLSKRQVPTMHIPVKTRRLLAALK
     511-532: APLPLGHIKRMQEVYNFNAINN → MAAALHSIQVGGRNSFGAKDGN
     533-611: Missing.
Isoform 4 (identifier: P09960-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MPEIVDTCSL...QSQEDNLRSL → MLPQRNLSKRQVPTMHIPVKTRRLLAALK
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10 Ref.11
Chain2 – 611610Leukotriene A-4 hydrolase
PRO_0000095124

Regions

Region135 – 1373Substrate binding
Region267 – 2726Substrate binding
Region564 – 5663Substrate binding

Sites

Active site2971Proton acceptor Probable
Active site3841Proton donor Probable
Metal binding2961Zinc; catalytic
Metal binding3001Zinc; catalytic
Metal binding3191Zinc; catalytic
Site3761Essential for epoxide hydrolase activity, but not for aminopeptidase activity
Site3791Covalently modified during suicide inhibition by leukotrienes

Amino acid modifications

Modified residue731N6-acetyllysine Ref.20
Modified residue3371N6-acetyllysine Ref.20
Modified residue4141N6-acetyllysine Ref.20
Modified residue4161Phosphoserine Ref.19
Modified residue5731N6-acetyllysine Ref.20

Natural variations

Alternative sequence1 – 5353MPEIV…NLRSL → MLPQRNLSKRQVPTMHIPVK TRRLLAALK in isoform 3 and isoform 4.
VSP_041107
Alternative sequence511 – 53222APLPL…NAINN → MAAALHSIQVGGRNSFGAKD GN in isoform 2 and isoform 3.
VSP_041108
Alternative sequence533 – 61179Missing in isoform 2 and isoform 3.
VSP_041109
Natural variant1311Y → H.
Corresponds to variant rs45630737 [ dbSNP | Ensembl ].
VAR_051570

Experimental info

Mutagenesis1351Q → A or L: Srongly increased epoxide hydrolase activity. Ref.16 Ref.26
Mutagenesis1351Q → A: Strongly reduced aminopeptidase activity. Strongly decreased affinity for leukotriene. Abolishes epoxide hydrolase activity. Ref.16 Ref.26
Mutagenesis1371Q → A: No loss of activity. Ref.16 Ref.25
Mutagenesis1371Q → L: Aminopeptidase activity strongly impaired, but keeps LTA4 activity. Ref.16 Ref.25
Mutagenesis1371Q → N: Aminopeptidase activity almost absent, but keeps LTA4 activity. Ref.16 Ref.25
Mutagenesis1401H → Q: Aminopeptidase activity almost absent, but keeps LTA4 activity. Ref.16 Ref.26
Mutagenesis2691G → A: No loss of activity. Ref.16
Mutagenesis2701G → A: No loss of activity. Ref.16 Ref.25
Mutagenesis2711M → L: No loss of activity. Ref.16 Ref.25
Mutagenesis2721E → A or D: Complete loss of activity. Ref.16 Ref.25
Mutagenesis2721E → Q: Loss of LTA4 activity, and aminopeptidase activity strongly impaired. Ref.16 Ref.25
Mutagenesis2731N → A: No loss of activity. Ref.16 Ref.25
Mutagenesis2961H → Y: Complete loss of activity. Ref.16
Mutagenesis2971E → A: Loss of both activities. Ref.16 Ref.17 Ref.18 Ref.28
Mutagenesis2971E → K: Loss of both activities. Ref.16 Ref.17 Ref.18 Ref.28
Mutagenesis2971E → Q: Loss of aminopeptidase activity, but keeps LTA4 activity. Ref.16 Ref.17 Ref.18 Ref.28
Mutagenesis3001H → L: Complete loss of activity. Ref.16
Mutagenesis3191E → A: Complete loss of activity. Ref.16
Mutagenesis3721D → N: No loss of activity. Ref.16 Ref.26
Mutagenesis3741D → N: No loss of activity. Ref.16 Ref.26
Mutagenesis3761D → A: Strongly reduced hydrolysis of peptides starting with Arg. Small effect on hydrolysis of peptides starting with Ala. Strongly reduced epoxide hydrolase activity. Ref.16 Ref.26 Ref.28
Mutagenesis3761D → E: Strongly reduced aminopeptidase activity. Abolishes epoxide hydrolase activity. Ref.16 Ref.26 Ref.28
Mutagenesis3761D → N: Abolishes aminopeptidase and epoxide hydrolase activity. Ref.16 Ref.26 Ref.28
Mutagenesis3851E → Q: Reduced aminopeptidase activity. Minor effect on epoxide hydrolase activity. Ref.16 Ref.26
Mutagenesis5641R → A, K or M: Abolishes epoxide hydrolase activity. Reduced aminopeptidase activity. Ref.16 Ref.27
Mutagenesis5661K → A or M: Strongly reduced affinity for peptide substrates. Reduced epoxide hydrolase and aminopeptidase activity. Ref.16 Ref.27
Mutagenesis5661K → R: No effect on epoxide hydrolase and aminopeptidase activity. Ref.16 Ref.27
Sequence conflict1151A → T in BX647158. Ref.6
Sequence conflict1231Q → R in BX647158. Ref.6
Sequence conflict2971E → G in BAG60321. Ref.4
Sequence conflict3091N → S in BX647158. Ref.6
Sequence conflict3781A → V in BX647158. Ref.6

Secondary structure

............................................................................................................... 611
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (L-LTA4) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 329BF6D04D4A06E1

FASTA61169,285
        10         20         30         40         50         60 
MPEIVDTCSL ASPASVCRTK HLHLRCSVDF TRRTLTGTAA LTVQSQEDNL RSLVLDTKDL 

        70         80         90        100        110        120 
TIEKVVINGQ EVKYALGERQ SYKGSPMEIS LPIALSKNQE IVIEISFETS PKSSALQWLT 

       130        140        150        160        170        180 
PEQTSGKEHP YLFSQCQAIH CRAILPCQDT PSVKLTYTAE VSVPKELVAL MSAIRDGETP 

       190        200        210        220        230        240 
DPEDPSRKIY KFIQKVPIPC YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SAYEFSETES 

       250        260        270        280        290        300 
MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH 

       310        320        330        340        350        360 
SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FNALGGWGEL QNSVKTFGET 

       370        380        390        400        410        420 
HPFTKLVVDL TDIDPDVAYS SVPYEKGFAL LFYLEQLLGG PEIFLGFLKA YVEKFSYKSI 

       430        440        450        460        470        480 
TTDDWKDFLY SYFKDKVDVL NQVDWNAWLY SPGLPPIKPN YDMTLTNACI ALSQRWITAK 

       490        500        510        520        530        540 
EDDLNSFNAT DLKDLSSHQL NEFLAQTLQR APLPLGHIKR MQEVYNFNAI NNSEIRFRWL 

       550        560        570        580        590        600 
RLCIQSKWED AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVRTYQ EHKASMHPVT 

       610 
AMLVGKDLKV D 

« Hide

Isoform 2 (S-LTA4) [UniParc].

Checksum: 474891F08B0215A8
Show »

FASTA53259,733
Isoform 3 [UniParc].

Checksum: A1CDA72AF83A875C
Show »

FASTA50857,300
Isoform 4 [UniParc].

Checksum: A70BF2792A0427C7
Show »

FASTA58766,852

References

« Hide 'large scale' references
[1]"Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis."
Minami M., Ohno S., Kawasaki H., Raedmark O., Samuelsson B., Joernvall H., Shimizu T., Seyama Y., Suzuki K.
J. Biol. Chem. 262:13873-13876(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Molecular cloning and amino acid sequence of leukotriene A4 hydrolase."
Funk C.D., Raadmark O., Fu J.Y., Matsumoto T., Joernvall H., Shimizu T., Samuelsson B.
Proc. Natl. Acad. Sci. U.S.A. 84:6677-6681(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[3]"Cloning and characterization of the human leukotriene A4 hydrolase gene."
Mancini J.A., Evans J.F.
Eur. J. Biochem. 231:65-71(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Lung.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Esophageal carcinoma.
[7]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Eye.
[10]"Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme."
Odlander B., Claesson H.E., Bergman T., Radmark O., Joernvall H., Haeggstrom J.Z.
Arch. Biochem. Biophys. 287:167-174(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-22, FUNCTION, CATALYTIC ACTIVITY.
Tissue: B-cell.
[11]"Leukotriene A4 hydrolase in human leukocytes. Purification and properties."
Radmark O., Shimizu T., Joernvall H., Samuelsson B.
J. Biol. Chem. 259:12339-12345(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16.
[12]"Leukotriene A4 hydrolase: mapping of a henicosapeptide involved in mechanism-based inactivation."
Mueller M.J., Wetterholm A., Blomster M., Jornvall H., Samuelsson B., Haeggstrom J.Z.
Proc. Natl. Acad. Sci. U.S.A. 92:8383-8387(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 366-386, ENZYME REGULATION, COVALENT MODIFICATION AT TYR-379, CATALYTIC ACTIVITY.
[13]"The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms."
Jendraschak E., Kaminski W.E., Kiefl R., von Schacky C.
Biochem. J. 314:733-737(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 511-611, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[14]"Molecular evolution and zinc ion binding motif of leukotriene A4 hydrolase."
Toh H., Minami M., Shimizu T.
Biochem. Biophys. Res. Commun. 171:216-221(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: ZINC-BINDING, FUNCTION AS A PEPTIDASE, SIMILARITY TO ZINC PROTEASES.
[15]"Leukotriene A4 hydrolase: a zinc metalloenzyme."
Haeggstroem J.Z., Wetterholm A., Shapiro R., Vallee B.L., Samuelsson B.
Biochem. Biophys. Res. Commun. 172:965-970(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: ZINC-BINDING, FUNCTION AS A PEPTIDASE.
[16]"Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site-directed mutagenesis and zinc analysis."
Medina J.F., Wetterholm A., Raadmark O., Shapiro R., Haeggstroem J.Z., Vallee B.L., Samuelsson B.
Proc. Natl. Acad. Sci. U.S.A. 88:7620-7624(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ZINC LIGANDS.
[17]"Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297."
Minami M., Bito H., Ohishi N., Tsuge H., Miyano M., Mori M., Wada H., Mutoh H., Shimada S., Izumi T., Abe K., Shimuzu T.
FEBS Lett. 309:353-357(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-297.
[18]"Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of glutamic acid-296."
Wetterholm A., Medina J.F., Raadmark O., Shapiro R., Haeggstroem J.Z., Vallee B.L., Samuelsson B.
Proc. Natl. Acad. Sci. U.S.A. 89:9141-9145(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-297.
[19]"Regulation of leukotriene A4 hydrolase activity in endothelial cells by phosphorylation."
Rybina I.V., Liu H., Gor Y., Feinmark S.J.
J. Biol. Chem. 272:31865-31871(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-416.
[20]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-337; LYS-414 AND LYS-573, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation."
Thunnissen M.M.G.M., Nordlund P., Haeggstroem J.Z.
Nat. Struct. Biol. 8:131-135(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[24]"Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors."
Thunnissen M.M., Andersson B., Samuelsson B., Wong C.H., Haeggstrom J.Z.
FASEB J. 16:1648-1650(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH CAPTOPRIL AND ZINC IONS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, ACTIVE SITE.
[25]"Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms."
Rudberg P.C., Tholander F., Thunnissen M.M.G.M., Haeggstroem J.Z.
J. Biol. Chem. 277:1398-1404(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT GLN-272, MUTAGENESIS OF GLN-137; GLY-270; MET-271; GLU-272 AND ASN-273.
[26]"Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375."
Rudberg P.C., Tholander F., Thunnissen M.M., Samuelsson B., Haeggstrom J.Z.
Proc. Natl. Acad. Sci. U.S.A. 99:4215-4220(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ASN-376 IN COMPLEX WITH BESTATIN AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLN-135; HIS-140; ASP-372; ASP-374; ASP-376 AND GLU-385.
[27]"Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates."
Rudberg P.C., Tholander F., Andberg M., Thunnissen M.M., Haeggstrom J.Z.
J. Biol. Chem. 279:27376-27382(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ALA-564 IN COMPLEX WITH ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, MUTAGENESIS OF ARG-564 AND LYS-566.
[28]"Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design."
Tholander F., Muroya A., Roques B.P., Fournie-Zaluski M.C., Thunnissen M.M., Haeggstrom J.Z.
Chem. Biol. 15:920-929(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF MUTANT GLN-297 IN COMPLEXES WITH SUBSTRATE TRIPEPTIDES AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, MUTAGENESIS OF GLU-297 AND ASP-376.
[29]"Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography."
Davies D.R., Mamat B., Magnusson O.T., Christensen J., Haraldsson M.H., Mishra R., Pease B., Hansen E., Singh J., Zembower D., Kim H., Kiselyov A.S., Burgin A.B., Gurney M.E., Stewart L.J.
J. Med. Chem. 52:4694-4715(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) IN COMPLEXES WITH INHIBITORS AND ZINC IONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03459 mRNA. Translation: AAA36176.1.
J02959 mRNA. Translation: AAA36177.1.
U27293 expand/collapse EMBL AC list , U27275, U27276, U27277, U27278, U27279, U27280, U27281, U27282, U27283, U27284, U27285, U27286, U27287, U27288, U27289, U27290, U27291, U27292 Genomic DNA. Translation: AAA89077.1.
AK298017 mRNA. Translation: BAG60321.1.
CR457068 mRNA. Translation: CAG33349.1.
BX647158 mRNA. No translation available.
AC007298 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97559.1.
BC032528 mRNA. Translation: AAH32528.1.
U43410 Genomic DNA. No translation available.
U43411 Genomic DNA. No translation available.
PIRS65947.
RefSeqNP_000886.1. NM_000895.2.
NP_001243572.1. NM_001256643.1.
NP_001243573.1. NM_001256644.1.
XP_005268928.1. XM_005268871.1.
UniGeneHs.524648.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GW6X-ray2.20A2-611[»]
1H19X-ray2.10A1-611[»]
1HS6X-ray1.95A1-611[»]
1SQMX-ray2.30A2-610[»]
2R59X-ray1.89A2-611[»]
2VJ8X-ray1.80A1-611[»]
3B7RX-ray1.81L2-611[»]
3B7SX-ray1.47A2-611[»]
3B7TX-ray2.30A2-611[»]
3B7UX-ray1.90X2-611[»]
3CHOX-ray1.80A2-611[»]
3CHPX-ray2.10A2-611[»]
3CHQX-ray2.09A2-611[»]
3CHRX-ray2.20A2-611[»]
3CHSX-ray2.55A2-611[»]
3FH5X-ray1.63A1-611[»]
3FH7X-ray2.05A1-611[»]
3FH8X-ray1.67A1-611[»]
3FHEX-ray2.16A1-611[»]
3FTSX-ray2.33A1-611[»]
3FTUX-ray1.90A1-611[»]
3FTVX-ray1.70A1-611[»]
3FTWX-ray1.85A1-611[»]
3FTXX-ray1.96A1-611[»]
3FTYX-ray2.15A1-611[»]
3FTZX-ray2.00A1-611[»]
3FU0X-ray1.80A1-611[»]
3FU3X-ray2.00A1-611[»]
3FU5X-ray2.30A1-611[»]
3FU6X-ray2.05A1-611[»]
3FUDX-ray2.20A1-611[»]
3FUEX-ray2.38A1-611[»]
3FUFX-ray2.60A1-611[»]
3FUHX-ray1.80A1-611[»]
3FUIX-ray2.20A1-611[»]
3FUJX-ray1.90A1-611[»]
3FUKX-ray1.95A1-611[»]
3FULX-ray2.39A1-611[»]
3FUMX-ray2.15A1-611[»]
3FUNX-ray1.58A1-611[»]
3U9WX-ray1.25A4-611[»]
4DPRX-ray2.02A1-611[»]
ProteinModelPortalP09960.
SMRP09960. Positions 4-611.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110226. 12 interactions.
IntActP09960. 5 interactions.
MINTMINT-1388946.
STRING9606.ENSP00000228740.

Chemistry

BindingDBP09960.
ChEMBLCHEMBL4618.
GuidetoPHARMACOLOGY1395.

Protein family/group databases

MEROPSM01.004.

PTM databases

PhosphoSiteP09960.

Polymorphism databases

DMDM126353.

2D gel databases

REPRODUCTION-2DPAGEIPI00219077.

Proteomic databases

PaxDbP09960.
PRIDEP09960.

Protocols and materials databases

DNASU4048.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228740; ENSP00000228740; ENSG00000111144. [P09960-1]
ENST00000413268; ENSP00000395051; ENSG00000111144. [P09960-3]
ENST00000552789; ENSP00000449958; ENSG00000111144. [P09960-4]
GeneID4048.
KEGGhsa:4048.
UCSCuc001ten.2. human. [P09960-1]
uc010suz.2. human. [P09960-3]

Organism-specific databases

CTD4048.
GeneCardsGC12M096394.
HGNCHGNC:6710. LTA4H.
HPACAB015221.
HPA008399.
HPA017017.
MIM151570. gene.
neXtProtNX_P09960.
PharmGKBPA24345.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0308.
HOGENOMHOG000293296.
HOVERGENHBG001274.
InParanoidP09960.
KOK01254.
OMAQEVKYTL.
OrthoDBEOG7SJD42.
PhylomeDBP09960.
TreeFamTF300758.

Enzyme and pathway databases

BioCycMetaCyc:HS03372-MONOMER.
BRENDA3.3.2.6. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00878.

Gene expression databases

ArrayExpressP09960.
BgeeP09960.
CleanExHS_LTA4H.
GenevestigatorP09960.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERPTHR11533. PTHR11533. 1 hit.
PfamPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSPR00756. ALADIPTASE.
SUPFAMSSF48371. SSF48371. 1 hit.
TIGRFAMsTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLTA4H. human.
EvolutionaryTraceP09960.
GenomeRNAi4048.
NextBio15856.
PROP09960.
SOURCESearch...

Entry information

Entry nameLKHA4_HUMAN
AccessionPrimary (citable) accession number: P09960
Secondary accession number(s): B4DNQ9 expand/collapse secondary AC list , F8VV40, Q6IAT6, Q9UCT7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM