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Q10740 (LKHA4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukotriene A-4 hydrolase homolog

Short name=LTA-4 hydrolase
EC=3.3.2.6
Alternative name(s):
Leucine aminopeptidase 2
Leukotriene A(4) hydrolase
Gene names
Name:LAP2
Ordered Locus Names:YNL045W
ORF Names:N2535
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length671 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Aminopeptidase that preferentially cleaves tripeptides. Also has low epoxide hydrolase activity (in vitro). Can hydrolyze an epoxide moiety of LTA4 to form LTB4 (in vitro). Ref.4 Ref.5 Ref.9 Ref.10 Ref.11

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.11

Cofactor

Binds 1 zinc ion per subunit. Ref.11

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 aminopeptidase activity is stimulated by LTA4. Ref.4 Ref.9

Pathway

Lipid metabolism; leukotriene B4 biosynthesis.

Subcellular location

Cytoplasm. Nucleus Ref.7.

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 Ref.4 Ref.5 Ref.10

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 671671Leukotriene A-4 hydrolase homolog
PRO_0000095129

Regions

Region184 – 1863Substrate binding
Region311 – 3166Substrate binding

Sites

Active site3411Proton acceptor
Active site4291Proton donor
Metal binding3401Zinc; catalytic
Metal binding3441Zinc; catalytic
Metal binding3631Zinc; catalytic

Experimental info

Mutagenesis2441Y → F: Reduces strongly the substrate affinity. Ref.10
Mutagenesis3161E → A, Q or D: Abolishes the aminopeptidase activity.
Mutagenesis3401H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities. Ref.5
Mutagenesis3411E → Q: Abolishes aminopeptidase activity. No effect on the epoxide hydrolase activity. Ref.5
Mutagenesis3441H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities. Ref.5
Mutagenesis3631E → Q: Abolishes the epoxide hydrolase activity. Ref.5
Mutagenesis4241F → Y: Increases the aminopeptidase activity and decreases the epoxide hydrolase activity. Ref.5
Mutagenesis4291Y → F: Abolishes the aminopeptidase activity and decreases the epoxide hydrolase activity. Ref.5
Mutagenesis6271R → K or A: Abolishes the aminopeptidase activity.

Secondary structure

.............................................................................................................................. 671
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q10740 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 454E40F030BF28FA

FASTA67177,353
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[3]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[4]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[5]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-340; GLU-341; HIS-344; GLU-363; PHE-424 AND TYR-429.
[6]"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] [Europe PMC] [Abstract]
Cited for: CRYSTALLIZATION.
[7]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[8]"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] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-244.
[11]"A leukotriene A4 hydrolase-related aminopeptidase from yeast undergoes induced fit upon inhibitor binding."
Helgstrand C., Hasan M., Uysal H., Haeggstrom J.Z., Thunnissen M.M.
J. Mol. Biol. 406:120-134(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 40-669 IN COMPLEX WITH ZINC IONS AND BESTATIN, CATALYTIC ACTIVITY, FUNCTION, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X94547 Genomic DNA. Translation: CAA64237.1.
Z71321 Genomic DNA. Translation: CAA95912.1.
BK006947 Genomic DNA. Translation: DAA10500.1.
PIRS61099.
RefSeqNP_014353.1. NM_001182884.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XPYX-ray2.73A40-671[»]
2XPZX-ray2.30A40-671[»]
2XQ0X-ray1.96A40-669[»]
ProteinModelPortalQ10740.
SMRQ10740. Positions 40-671.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid35779. 25 interactions.
DIPDIP-4371N.
IntActQ10740. 6 interactions.
MINTMINT-542331.
STRING4932.YNL045W.

Protein family/group databases

MEROPSM01.034.

Proteomic databases

MaxQBQ10740.
PaxDbQ10740.
PeptideAtlasQ10740.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYNL045W; YNL045W; YNL045W.
GeneID855682.
KEGGsce:YNL045W.

Organism-specific databases

CYGDYNL045w.
SGDS000004990. LAP2.

Phylogenomic databases

eggNOGCOG0308.
GeneTreeENSGT00530000063003.
HOGENOMHOG000293296.
KOK01254.
OMASPASVCQ.
OrthoDBEOG7DFXMZ.

Enzyme and pathway databases

BioCycYEAST:YNL045W-MONOMER.
UniPathwayUPA00878.

Gene expression databases

GenevestigatorQ10740.

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

EvolutionaryTraceQ10740.
NextBio979984.
PROQ10740.

Entry information

Entry nameLKHA4_YEAST
AccessionPrimary (citable) accession number: Q10740
Secondary accession number(s): D6W1D4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 11, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome XIV

Yeast (Saccharomyces cerevisiae) chromosome XIV: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

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