Reviewed, UniProtKB/Swiss-Prot P24527 (LKHA4_MOUSE)

Names and origin

Protein names

Recommended name:
    Leukotriene A-4 hydrolase
    EC=3.3.2.6
Alternative name(s):
    Leukotriene A(4) hydrolase
      Short name=LTA-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

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	Hydrolyzes an epoxide moiety of leukotriene A4 (LTA-4) to form leukotriene B4 (LTB-4). The enzyme also has some peptidase activity.
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.
Cofactor	Binds 1 zinc ion per subunit.
Pathway	Lipid metabolism; leukotriene B4 biosynthesis.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase M1 family.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Acetylation
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	leukotriene-A4 hydrolase activity Inferred from electronic annotation. Source: EC metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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
Sites
	Active site	297	1	By similarity
	Active site	384	1	Proton donor Potential
	Metal binding	296	1	Zinc; catalytic
	Metal binding	300	1	Zinc; catalytic
	Metal binding	319	1	Zinc; catalytic
	Binding site	200	1	Substrate 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.3
	Mutagenesis	300	1	H → Y: Complete loss of activity. Ref.3
	Mutagenesis	319	1	E → Q: Complete loss of activity. Ref.3
	Sequence conflict	593	1	K → R Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P24527-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 6CE9C20F630EB4C9	FASTA	611	69,021
	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 NQVDWNAWLY 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 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].
[3]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M63848 mRNA. Translation: AAB59675.1. Sequence problems. BC021417 mRNA. Translation: AAH21417.1.
IPI	IPI00229527.
PIR	JN0066.
UniGene	Mm.271071
3D structure databases
HSSP	HSSP built from PDB template 1HS6 based on UniProtKB P09960.
SMR	P24527. Positions 2-611.
ModBase	Search...
Protein-protein interaction databases
STRING	P24527.
Protein family/group databases
MEROPS	M01.004.
PTM databases
PhosphoSite	P24527.
Proteomic databases
PRIDE	P24527.
Genome annotation databases
Ensembl	ENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889; Mus musculus. [Genome view]
Organism-specific databases
MGI	MGI:96836. Lta4h.
Phylogenomic databases
HOGENOM	P24527.
HOVERGEN	P24527.
Enzyme and pathway databases
BRENDA	3.3.2.6. 244.
Gene expression databases
ArrayExpress	P24527.
Bgee	P24527.
CleanEx	MM_LTA4H.
Genevestigator	P24527.
GermOnline	ENSMUSG00000015889. Mus musculus.
Family and domain databases
InterPro	IPR012777. Leuk_A4_hydro_aminopept. IPR006025. Pept_M_Zn_BS. IPR001930. Peptidase_M1. IPR015211. Peptidase_M1_C. IPR014782. Peptidase_M1_N. [Graphical view]
PANTHER	PTHR11533. Peptidase_M1. 1 hit.
Pfam	PF09127. Leuk-A4-hydro_C. 1 hit. PF01433. Peptidase_M1. 1 hit. [Graphical view]
PRINTS	PR00756. ALADIPTASE.
TIGRFAMs	TIGR02411. leuko_A4_hydro. 1 hit.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

LKHA4_MOUSE

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)