Reviewed, UniProtKB/Swiss-Prot Q10740 (LKHA4_YEAST)

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

Ordered Locus Names:	YNL045W
ORF Names:	N2535

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	671 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Hydrolyzes an epoxide moiety of LTA(4) to form LTB(4). The enzyme also has aminopeptidase activity.
Catalytic activity	(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Inhibited 3-(4-benzyloxyphenyl)-2-(R)-amino-1-propanethiol (thioamine) and N-hydroxy-N-(2-(S)-amino-3-(4-benzyloxyphenyl)propyl)-5-carboxypen-tanamide (hydroxamic acid). The amiminopeptidase activity is stimulated by LTA(4).
Pathway	Lipid metabolism; leukotriene B4 biosynthesis.
Subcellular location	Cytoplasm. Nucleus.
Miscellaneous	Present with 5590 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the peptidase M1 family.
Biophysicochemical properties	Kinetic parameters: KM=1.5 mM for Leu-p-nitroanilide KM=1.8 mM for Met-p-nitroanilide KM=2.0 mM for Ala-p-nitroanilide Vmax=520 nmol/min/mg enzyme with Leu-p-nitroanilide as substrate Vmax=360 nmol/min/mg enzyme with Met-p-nitroanilide as substrate Vmax=170 nmol/min/mg enzyme with Ala-p-nitroanilide as substrate pH dependence: Optimum pH is about 7.3.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	leukotriene biosynthetic process Inferred from electronic annotation. Source: InterPro protein catabolic process Ref.3 Inferred from direct assay. Source: SGD proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Ref.6 Inferred from electronic annotation. Source: UniProtKB-KW nucleus Ref.6 Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	aminopeptidase activity Ref.3 Inferred from direct assay. Source: SGD epoxide hydrolase activity Ref.3 Inferred from direct assay. Source: SGD leukotriene-A4 hydrolase activity Inferred from electronic annotation. Source: InterPro metallopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRP40	P33203	1	EBI-10175,EBI-701
RSP5	P39940	1	EBI-10175,EBI-16219
SSM4	P40318	1	EBI-10175,EBI-18208

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 671	671	Leukotriene A-4 hydrolase		PRO_0000095129
Sites
	Active site	341	1
	Active site	429	1	Proton donor
	Metal binding	340	1	Zinc; catalytic
	Metal binding	344	1	Zinc; catalytic
	Metal binding	363	1	Zinc; catalytic
	Site	244	1	Transition state stabilizer
Amino acid modifications
	Modified residue	51	1	Phosphoserine
Experimental info
	Mutagenesis	244	1	Y → F: Reduces strongly the substrate affinity
	Mutagenesis	316	1	E → A, Q or D: Abolishes the aminopeptidase activity
	Mutagenesis	340	1	H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities
	Mutagenesis	341	1	E → Q: Abolishes the epoxide hydrolase and aminopeptidase activities
	Mutagenesis	344	1	H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities
	Mutagenesis	363	1	E → Q: Abolishes the epoxide hydrolase activity
	Mutagenesis	424	1	F → Y: Increases the epoxide hydrolase activity and decreases the aminopeptidase activity
	Mutagenesis	429	1	Y → F: Abolishes the epoxide hydrolase activity and decreases the aminopeptidase activity
	Mutagenesis	627	1	R → K or A: Abolishes the aminopeptidase activity

Sequences

	Sequence		Length	Mass (Da)
	Q10740-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 454E40F030BF28FA	FASTA	671	77,353
	10 20 30 40 50 60 MFLLPFVIRH SSSIYLPTLR FRGLLTVISR NIHISTPHKM LPLSIEQRRP SRSPEYDQST 70 80 90 100 110 120 LSNYKDFAVL HTDLNLSVSF EKSAISGSVT FQLKKLHEGK NKSDELHLDT SYLDVQEVHI 130 140 150 160 170 180 DGSKADFQIE QRKEPLGSRL VINNASCNDN FTLNIQFRTT DKCTALQWLN SKQTKGGKPY 190 200 210 220 230 240 VFSQLEAIHA RSLFPCFDTP SVKSTFTASI ESPLPVVFSG IRIEDTSKDT NIYRFEQKVP 250 260 270 280 290 300 IPAYLIGIAS GDLSSAPIGP RSTVYTEPFR LKDCQWEFEN DVEKFIQTAE KIIFEYEWGT 310 320 330 340 350 360 YDILVNVDSY PYGGMESPNM TFATPTLIAH DRSNIDVIAH ELAHSWSGNL VTNCSWNHFW 370 380 390 400 410 420 LNEGWTVYLE RRIIGAIHGE PTRHFSALIG WSDLQNSIDS MKDPERFSTL VQNLNDNTDP 430 440 450 460 470 480 DDAFSTVPYE KGFNLLFHLE TILGGKAEFD PFIRHYFKKF AKKSLDTFQF LDTLYEFYPE 490 500 510 520 530 540 KKEILDSVDW ETWLYKPGMP PRPHFITALA DNVYQLADKW VEMAQHLKTT EDFRSEFNAI 550 560 570 580 590 600 DIKDFNSNQL VLFLETLTQN GHSNKKPKDF DWAKFPVASR ALLDIYQDNI VKSQNAEVVF 610 620 630 640 650 660 KMFKFQIFAK LQEEYKHLAD WLGTVGRMKF VRPGYRLLNS VDRRLALATF DKFKDTYHPI 670 CKALVKQDLG L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The sequence of 12.8 kb from the left arm of chromosome XIV reveals a sigma element, a pro-tRNA and six complete open reading frames, one of which encodes a protein similar to the human leukotriene A4 hydrolase." Nasr F., Becam A.-M., Herbert C.J. Yeast 12:493-499(1996) [PubMed: 8740423] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications." Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., Beinhauer J.D., Boskovic J., Buitrago M.J. , Bussereau F., Coster F., Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J. Nature 387:93-98(1997) [PubMed: 9169873] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	"Cloning and characterization of a bifunctional leukotriene A(4) hydrolase from Saccharomyces cerevisiae." Kull F., Ohlson E., Haeggstroem J.Z. J. Biol. Chem. 274:34683-34690(1999) [PubMed: 10574934] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[4]	"Saccharomyces cerevisiae leukotriene A4 hydrolase: formation of leukotriene B4 and identification of catalytic residues." Kull F., Ohlson E., Lind B., Haeggstroem J.Z. Biochemistry 40:12695-12703(2001) [PubMed: 11601994] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-340; GLU-341; HIS-344; GLU-363; PHE-424 AND TYR-429.
[5]	"Crystallization and X-ray diffraction data analysis of leukotriene A4 hydrolase from Saccharomyces cerevisiae." Andersson B., Kull F., Haeggstroem J.Z., Thunnissen M.M.G.M. Acta Crystallogr. D 59:1093-1095(2003) [PubMed: 12777785] [Abstract] Cited for: CRYSTALLIZATION.
[6]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[7]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[8]	"Leukotriene A4 hydrolase, insights into the molecular evolution by homology modeling and mutational analysis of enzyme from Saccharomyces cerevisiae." Tholander F., Kull F., Ohlson E., Shafqat J., Thunnissen M.M.G.M., Haeggstroem J.Z. J. Biol. Chem. 280:33477-33486(2005) [PubMed: 16024909] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS.
[9]	"A conserved tyrosine residue of Saccharomyces cerevisiae leukotriene A4 hydrolase stabilizes the transition state of the peptidase activity." Thompson M.W., Archer E.D., Romer C.E., Seipelt R.L. Peptides 27:1701-1709(2006) [PubMed: 16597475] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-244.
[10]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X94547 Genomic DNA. Translation: CAA64237.1. Z71321 Genomic DNA. Translation: CAA95912.1.
PIR	S61099.
RefSeq	NP_014353.1.
3D structure databases
HSSP	HSSP built from PDB template 1HS6 based on UniProtKB P09960.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:4371N.
IntAct	Q10740.
Proteomic databases
PeptideAtlas	Q10740.
Genome annotation databases
Ensembl	YNL045W. Saccharomyces cerevisiae. [Contig view]
GeneID	855682.
GenomeReviews	Gene locus YNL045W in contig Y13139_GR.
KEGG	sce:YNL045W.
NMPDR	fig|4932.3.peg.5429.
Organism-specific databases
CYGD	YNL045w.
SGD	S000004990. YNL045W.
Yeast-GFP	Search...
Phylogenomic databases
HOGENOM	Q10740.
Gene expression databases
GermOnline	YNL045W. Saccharomyces cerevisiae.
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
LinkHub	Q10740.
NextBio	979984.

Entry information

Entry name

LKHA4_YEAST

Accession

Primary (citable) accession number: Q10740

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)