P24527 (LKHA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	611 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.5
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.5
Cofactor	Binds 1 zinc ion per subunit.
Enzyme regulation	Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4. Ref.5
Pathway	Lipid metabolism; leukotriene B4 biosynthesis.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase M1 family.
Biophysicochemical properties	Kinetic parameters: KM=5 µM for leukotriene A4 Ref.5 Vmax=1030 nmol/min/mg enzyme for leukotriene A4

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	leukotriene biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB peptide catabolic process Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aminopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB epoxide hydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB leukotriene-A4 hydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 611	610	Leukotriene A-4 hydrolase		PRO_0000095125
Regions
	Region	135 – 137	3	Substrate binding By similarity
	Region	267 – 272	6	Substrate binding By similarity
	Region	564 – 566	3	Substrate binding By similarity
Sites
	Active site	297	1	Proton acceptor By similarity
	Active site	384	1	Proton donor By similarity
	Metal binding	296	1	Zinc; catalytic
	Metal binding	300	1	Zinc; catalytic
	Metal binding	319	1	Zinc; catalytic
	Site	376	1	Essential for epoxide hydrolase activity, but not for aminopeptidase activity By similarity
	Site	379	1	Covalently modified during suicide inhibition by leukotrienes By similarity
Amino acid modifications
	Modified residue	73	1	N6-acetyllysine By similarity
	Modified residue	337	1	N6-acetyllysine By similarity
	Modified residue	414	1	N6-acetyllysine By similarity
	Modified residue	573	1	N6-acetyllysine By similarity
Experimental info
	Mutagenesis	296	1	H → Y: Complete loss of activity. Ref.4
	Mutagenesis	300	1	H → Y: Complete loss of activity. Ref.4
	Mutagenesis	319	1	E → Q: Complete loss of activity. Ref.4
	Mutagenesis	384	1	Y → F, H or Q: Alters leukotriene hydrolase activity, strongly enhancing the formation of a metabolite that is normally produced in trace amounts. Ref.4 Ref.5
	Sequence conflict	447	1	T → A in AAB59675. Ref.1
	Sequence conflict	447	1	T → A in AAH21417. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P24527 [UniParc]. Last modified July 27, 2011. Version 4. Checksum: CCF8D30F6FA9721E	FASTA	611	69,051
	10 20 30 40 50 60 MPEVADTCSL ASPASVCRTQ HLHLRCSVDF ARRTLTGTAA LTVQSQEENL RSLTLDTKDL 70 80 90 100 110 120 TIEKVVINGQ EVKYTLGESQ GYKGSPMEIS LPIALSKNQE IVIEISFETS PKSSALQWLT 130 140 150 160 170 180 PEQTSGKQHP YLFSQCQAIH CRAILPCQDT PSVKLTYTAE VSVPKELVAL MSAIRDGEAP 190 200 210 220 230 240 DPEDPSRKIY RFNQRVPIPC YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SANEFSETES 250 260 270 280 290 300 MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH 310 320 330 340 350 360 SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FHALGGWGEL QNTIKTFGES 370 380 390 400 410 420 HPFTKLVVDL KDVDPDVAYS SIPYEKGFAL LFYLEQLLGG PEVFLGFLKA YVKKFSYQSV 430 440 450 460 470 480 TTDDWKSFLY SHFKDKVDLL NQVDWNTWLY APGLPPVKPN YDVTLTNACI ALSQRWVTAK 490 500 510 520 530 540 EEDLSSFSIA DLKDLSSHQL NEFLAQVLQK APLPLGHIKR MQEVYNFNAI NNSEIRFRWL 550 560 570 580 590 600 RLCIQSKWEE AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVHTYQ EHKASMHPVT 610 AMLVGRDLKV D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of mouse leukotriene A4 hydrolase cDNA." Medina J.F., Raadmark O., Funk C.D., Haeggstroem J.Z. Biochem. Biophys. Res. Commun. 176:1516-1524(1991) [PubMed: 1710117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Olfactory bulb.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 1881903] [Abstract] Cited for: MUTAGENESIS OF ZINC LIGANDS.
[5]	"Mutation of tyrosine 383 in leukotriene A4 hydrolase allows conversion of leukotriene A4 into 5S,6S-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acid. Implications for the epoxide hydrolase mechanism." Andberg M.B., Hamberg M., Haeggstrom J.Z. J. Biol. Chem. 272:23057-23063(1997) [PubMed: 9287304] [Abstract] Cited for: MUTAGENESIS OF TYR-384, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M63848 mRNA. Translation: AAB59675.1. AK134931 mRNA. Translation: BAE22342.1. BC021417 mRNA. Translation: AAH21417.1.
IPI	IPI00229527.
PIR	JN0066.
RefSeq	NP_032543.2. NM_008517.2.
UniGene	Mm.271071.
3D structure databases
ProteinModelPortal	P24527.
SMR	P24527. Positions 6-610.
ModBase	Search...
Protein-protein interaction databases
STRING	P24527.
Protein family/group databases
MEROPS	M01.004.
PTM databases
PhosphoSite	P24527.
Proteomic databases
PRIDE	P24527.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889.
GeneID	16993.
KEGG	mmu:16993.
Organism-specific databases
CTD	4048.
MGI	MGI:96836. Lta4h.
Phylogenomic databases
eggNOG	roNOG05312.
HOGENOM	HBG444814.
HOVERGEN	HBG001274.
InParanoid	P24527.
OrthoDB	EOG40GCQC.
PhylomeDB	P24527.
Gene expression databases
ArrayExpress	P24527.
Bgee	P24527.
CleanEx	MM_LTA4H.
Genevestigator	P24527.
GermOnline	ENSMUSG00000015889. Mus musculus.
Family and domain databases
InterPro	IPR016024. ARM-type_fold. IPR012777. Leukotriene_A4_hydrolase. IPR001930. Peptidase_M1. IPR015211. Peptidase_M1_C. IPR014782. Peptidase_M1_N. [Graphical view]
KO	K01254.
PANTHER	PTHR11533. Peptidase_M1. 1 hit.
Pfam	PF09127. Leuk-A4-hydro_C. 1 hit. PF01433. Peptidase_M1. 1 hit. [Graphical view]
PRINTS	PR00756. ALADIPTASE.
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
TIGRFAMs	TIGR02411. Leuko_A4_hydro. 1 hit.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

LKHA4_MOUSE

Accession

Primary (citable) accession number: P24527
Secondary accession number(s): Q3UY71, Q8VDR8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 116 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program