Leukotriene A-4 hydrolase - Mus musculus (Mouse)

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P24527 (LKHA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 128. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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) [Reference proteome]

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.
Post-translational modification	Phosphorylation at Ser-416 inhibits enzymatic activity By similarity.
Sequence similarities	Belongs to the peptidase M1 family.
Biophysicochemical properties	Kinetic parameters: K_M=5 µM for leukotriene A4 Ref.5 V_max=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 Phosphoprotein
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 nucleus Inferred from electronic annotation. Source: Compara
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

Removed By similarity

Chain

2 – 611

610

Leukotriene A-4 hydrolase

PRO_0000095125

Regions

Region

135 – 137

Substrate binding By similarity

Region

267 – 272

Substrate binding By similarity

Region

564 – 566

Substrate binding By similarity

Sites

Active site

297

Proton acceptor By similarity

Active site

384

Proton donor By similarity

Metal binding

296

Zinc; catalytic

Metal binding

300

Zinc; catalytic

Metal binding

319

Zinc; catalytic

Site

376

Essential for epoxide hydrolase activity, but not for aminopeptidase activity By similarity

Site

379

Covalently modified during suicide inhibition by leukotrienes By similarity

Amino acid modifications

Modified residue

N6-acetyllysine By similarity

Modified residue

337

N6-acetyllysine By similarity

Modified residue

414

N6-acetyllysine By similarity

Modified residue

416

Phosphoserine By similarity

Modified residue

573

N6-acetyllysine By similarity

Experimental info

Mutagenesis

296

H → Y: Complete loss of activity. Ref.4

Mutagenesis

300

H → Y: Complete loss of activity. Ref.4

Mutagenesis

319

E → Q: Complete loss of activity. Ref.4

Mutagenesis

384

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

T → A in AAB59675. Ref.1

Sequence conflict

447

T → A in AAH21417. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

P24527 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: CCF8D30F6FA9721E
Show »

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

« Hide

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] [Europe PMC] [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. Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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	10090.ENSMUSP00000016033.
Protein family/group databases
MEROPS	M01.004.
PTM databases
PhosphoSite	P24527.
Proteomic databases
PaxDb	P24527.
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	COG0308.
GeneTree	ENSGT00530000063003.
HOGENOM	HOG000293296.
HOVERGEN	HBG001274.
InParanoid	Q3UY71.
KO	K01254.
OMA	QEVKYTL.
OrthoDB	EOG40GCQC.
Enzyme and pathway databases
UniPathway	UPA00878.
Gene expression databases
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]
PANTHER	PTHR11533. PTHR11533. 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
ChEMBL	CHEMBL3738.
NextBio	291088.
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:	May 1, 2013
This is version 128 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents