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Q10740

- LKHA4_YEAST

UniProt

Q10740 - LKHA4_YEAST

Protein

Leukotriene A-4 hydrolase homolog

Gene

LAP2

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    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).5 Publications

    Catalytic activityi

    (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.1 Publication

    Cofactori

    Binds 1 zinc ion per subunit.1 Publication

    Enzyme regulationi

    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 LTA4.2 Publications

    Kineticsi

    1. KM=1.5 mM for Leu-p-nitroanilide3 Publications
    2. KM=1.8 mM for Met-p-nitroanilide3 Publications
    3. KM=2.0 mM for Ala-p-nitroanilide3 Publications

    Vmax=520 nmol/min/mg enzyme with Leu-p-nitroanilide as substrate3 Publications

    Vmax=360 nmol/min/mg enzyme with Met-p-nitroanilide as substrate3 Publications

    Vmax=170 nmol/min/mg enzyme with Ala-p-nitroanilide as substrate3 Publications

    pH dependencei

    Optimum pH is about 7.3.3 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi340 – 3401Zinc; catalytic
    Active sitei341 – 3411Proton acceptor
    Metal bindingi344 – 3441Zinc; catalytic
    Metal bindingi363 – 3631Zinc; catalytic
    Active sitei429 – 4291Proton donor

    GO - Molecular functioni

    1. aminopeptidase activity Source: SGD
    2. epoxide hydrolase activity Source: SGD
    3. leukotriene-A4 hydrolase activity Source: SGD
    4. metallopeptidase activity Source: UniProtKB-KW
    5. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cellular lipid metabolic process Source: SGD
    2. leukotriene biosynthetic process Source: UniProtKB-KW
    3. peptide catabolic process Source: UniProtKB
    4. protein catabolic process Source: SGD

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Leukotriene biosynthesis

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciYEAST:YNL045W-MONOMER.
    ReactomeiREACT_189270. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    UniPathwayiUPA00878.

    Protein family/group databases

    MEROPSiM01.034.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Leukotriene A-4 hydrolase homolog (EC:3.3.2.6)
    Short name:
    LTA-4 hydrolase
    Alternative name(s):
    Leucine aminopeptidase 2
    Leukotriene A(4) hydrolase
    Gene namesi
    Name:LAP2
    Ordered Locus Names:YNL045W
    ORF Names:N2535
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311: Chromosome XIV

    Organism-specific databases

    CYGDiYNL045w.
    SGDiS000004990. LAP2.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi244 – 2441Y → F: Reduces strongly the substrate affinity. 2 Publications
    Mutagenesisi316 – 3161E → A, Q or D: Abolishes the aminopeptidase activity. 1 Publication
    Mutagenesisi340 – 3401H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities. 2 Publications
    Mutagenesisi341 – 3411E → Q: Abolishes aminopeptidase activity. No effect on the epoxide hydrolase activity. 2 Publications
    Mutagenesisi344 – 3441H → Q: Abolishes the epoxide hydrolase and aminopeptidase activities. 2 Publications
    Mutagenesisi363 – 3631E → Q: Abolishes the epoxide hydrolase activity. 2 Publications
    Mutagenesisi424 – 4241F → Y: Increases the aminopeptidase activity and decreases the epoxide hydrolase activity. 2 Publications
    Mutagenesisi429 – 4291Y → F: Abolishes the aminopeptidase activity and decreases the epoxide hydrolase activity. 2 Publications
    Mutagenesisi627 – 6271R → K or A: Abolishes the aminopeptidase activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 671671Leukotriene A-4 hydrolase homologPRO_0000095129Add
    BLAST

    Proteomic databases

    MaxQBiQ10740.
    PaxDbiQ10740.
    PeptideAtlasiQ10740.

    Expressioni

    Gene expression databases

    GenevestigatoriQ10740.

    Interactioni

    Protein-protein interaction databases

    BioGridi35779. 25 interactions.
    DIPiDIP-4371N.
    IntActiQ10740. 6 interactions.
    MINTiMINT-542331.
    STRINGi4932.YNL045W.

    Structurei

    Secondary structure

    1
    671
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi43 – 486
    Beta strandi51 – 544
    Helixi64 – 663
    Beta strandi67 – 7913
    Turni80 – 834
    Beta strandi84 – 9512
    Beta strandi99 – 1013
    Beta strandi105 – 1095
    Beta strandi111 – 12010
    Beta strandi127 – 1293
    Turni134 – 1363
    Beta strandi140 – 1434
    Beta strandi147 – 15913
    Beta strandi164 – 1696
    Turni171 – 1733
    Beta strandi175 – 1784
    Beta strandi180 – 1834
    Turni186 – 1894
    Helixi190 – 1923
    Beta strandi204 – 2118
    Beta strandi216 – 2227
    Beta strandi232 – 24110
    Helixi243 – 2453
    Beta strandi248 – 2525
    Beta strandi254 – 2596
    Beta strandi262 – 2665
    Helixi268 – 27811
    Turni279 – 2813
    Helixi282 – 29211
    Beta strandi297 – 2993
    Beta strandi303 – 3053
    Beta strandi312 – 3154
    Beta strandi321 – 3233
    Helixi325 – 3273
    Beta strandi330 – 3323
    Helixi336 – 3449
    Turni348 – 3503
    Beta strandi351 – 3555
    Helixi356 – 3594
    Helixi360 – 37819
    Helixi380 – 39920
    Beta strandi401 – 4033
    Helixi404 – 4074
    Beta strandi409 – 4113
    Beta strandi416 – 4183
    Helixi420 – 4234
    Helixi427 – 44216
    Helixi446 – 45914
    Turni460 – 4623
    Beta strandi463 – 4653
    Helixi467 – 47711
    Helixi479 – 4813
    Helixi482 – 4865
    Helixi490 – 4956
    Helixi508 – 52316
    Turni524 – 5263
    Helixi530 – 5367
    Helixi539 – 5424
    Helixi547 – 55812
    Beta strandi562 – 5654
    Helixi572 – 5743
    Helixi576 – 58510
    Helixi587 – 5915
    Helixi596 – 60813
    Helixi612 – 6143
    Helixi615 – 6217
    Turni622 – 6243
    Helixi628 – 63912
    Helixi643 – 65311
    Helixi654 – 6563
    Helixi659 – 66810

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2XPYX-ray2.73A40-671[»]
    2XPZX-ray2.30A40-671[»]
    2XQ0X-ray1.96A40-669[»]
    ProteinModelPortaliQ10740.
    SMRiQ10740. Positions 40-671.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ10740.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni184 – 1863Substrate binding
    Regioni311 – 3166Substrate binding

    Sequence similaritiesi

    Belongs to the peptidase M1 family.Curated

    Phylogenomic databases

    eggNOGiCOG0308.
    GeneTreeiENSGT00530000063003.
    HOGENOMiHOG000293296.
    KOiK01254.
    OMAiSPASVCQ.
    OrthoDBiEOG7DFXMZ.

    Family and domain databases

    InterProiIPR016024. ARM-type_fold.
    IPR012777. Leukotriene_A4_hydrolase.
    IPR001930. Peptidase_M1.
    IPR015211. Peptidase_M1_C.
    IPR014782. Peptidase_M1_N.
    [Graphical view]
    PANTHERiPTHR11533. PTHR11533. 1 hit.
    PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
    PF01433. Peptidase_M1. 1 hit.
    [Graphical view]
    PRINTSiPR00756. ALADIPTASE.
    SUPFAMiSSF48371. SSF48371. 1 hit.
    TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q10740-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFLLPFVIRH SSSIYLPTLR FRGLLTVISR NIHISTPHKM LPLSIEQRRP    50
    SRSPEYDQST LSNYKDFAVL HTDLNLSVSF EKSAISGSVT FQLKKLHEGK 100
    NKSDELHLDT SYLDVQEVHI DGSKADFQIE QRKEPLGSRL VINNASCNDN 150
    FTLNIQFRTT DKCTALQWLN SKQTKGGKPY VFSQLEAIHA RSLFPCFDTP 200
    SVKSTFTASI ESPLPVVFSG IRIEDTSKDT NIYRFEQKVP IPAYLIGIAS 250
    GDLSSAPIGP RSTVYTEPFR LKDCQWEFEN DVEKFIQTAE KIIFEYEWGT 300
    YDILVNVDSY PYGGMESPNM TFATPTLIAH DRSNIDVIAH ELAHSWSGNL 350
    VTNCSWNHFW LNEGWTVYLE RRIIGAIHGE PTRHFSALIG WSDLQNSIDS 400
    MKDPERFSTL VQNLNDNTDP DDAFSTVPYE KGFNLLFHLE TILGGKAEFD 450
    PFIRHYFKKF AKKSLDTFQF LDTLYEFYPE KKEILDSVDW ETWLYKPGMP 500
    PRPHFITALA DNVYQLADKW VEMAQHLKTT EDFRSEFNAI DIKDFNSNQL 550
    VLFLETLTQN GHSNKKPKDF DWAKFPVASR ALLDIYQDNI VKSQNAEVVF 600
    KMFKFQIFAK LQEEYKHLAD WLGTVGRMKF VRPGYRLLNS VDRRLALATF 650
    DKFKDTYHPI CKALVKQDLG L 671
    Length:671
    Mass (Da):77,353
    Last modified:October 1, 1996 - v1
    Checksum:i454E40F030BF28FA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X94547 Genomic DNA. Translation: CAA64237.1.
    Z71321 Genomic DNA. Translation: CAA95912.1.
    BK006947 Genomic DNA. Translation: DAA10500.1.
    PIRiS61099.
    RefSeqiNP_014353.1. NM_001182884.1.

    Genome annotation databases

    EnsemblFungiiYNL045W; YNL045W; YNL045W.
    GeneIDi855682.
    KEGGisce:YNL045W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X94547 Genomic DNA. Translation: CAA64237.1 .
    Z71321 Genomic DNA. Translation: CAA95912.1 .
    BK006947 Genomic DNA. Translation: DAA10500.1 .
    PIRi S61099.
    RefSeqi NP_014353.1. NM_001182884.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2XPY X-ray 2.73 A 40-671 [» ]
    2XPZ X-ray 2.30 A 40-671 [» ]
    2XQ0 X-ray 1.96 A 40-669 [» ]
    ProteinModelPortali Q10740.
    SMRi Q10740. Positions 40-671.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 35779. 25 interactions.
    DIPi DIP-4371N.
    IntActi Q10740. 6 interactions.
    MINTi MINT-542331.
    STRINGi 4932.YNL045W.

    Protein family/group databases

    MEROPSi M01.034.

    Proteomic databases

    MaxQBi Q10740.
    PaxDbi Q10740.
    PeptideAtlasi Q10740.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YNL045W ; YNL045W ; YNL045W .
    GeneIDi 855682.
    KEGGi sce:YNL045W.

    Organism-specific databases

    CYGDi YNL045w.
    SGDi S000004990. LAP2.

    Phylogenomic databases

    eggNOGi COG0308.
    GeneTreei ENSGT00530000063003.
    HOGENOMi HOG000293296.
    KOi K01254.
    OMAi SPASVCQ.
    OrthoDBi EOG7DFXMZ.

    Enzyme and pathway databases

    UniPathwayi UPA00878 .
    BioCyci YEAST:YNL045W-MONOMER.
    Reactomei REACT_189270. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Miscellaneous databases

    EvolutionaryTracei Q10740.
    NextBioi 979984.
    PROi Q10740.

    Gene expression databases

    Genevestigatori Q10740.

    Family and domain databases

    InterProi IPR016024. ARM-type_fold.
    IPR012777. Leukotriene_A4_hydrolase.
    IPR001930. Peptidase_M1.
    IPR015211. Peptidase_M1_C.
    IPR014782. Peptidase_M1_N.
    [Graphical view ]
    PANTHERi PTHR11533. PTHR11533. 1 hit.
    Pfami PF09127. Leuk-A4-hydro_C. 1 hit.
    PF01433. Peptidase_M1. 1 hit.
    [Graphical view ]
    PRINTSi PR00756. ALADIPTASE.
    SUPFAMi SSF48371. SSF48371. 1 hit.
    TIGRFAMsi TIGR02411. leuko_A4_hydro. 1 hit.
    PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    8. 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.

    Entry informationi

    Entry nameiLKHA4_YEAST
    AccessioniPrimary (citable) accession number: Q10740
    Secondary accession number(s): D6W1D4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 141 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 5590 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families
    5. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    6. Yeast chromosome XIV
      Yeast (Saccharomyces cerevisiae) chromosome XIV: entries and gene names

    External Data

    Dasty 3