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P20292

- AL5AP_HUMAN

UniProt

P20292 - AL5AP_HUMAN

Protein

Arachidonate 5-lipoxygenase-activating protein

Gene

ALOX5AP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 2 (01 Dec 1992)
      Previous versions | rss
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    Functioni

    Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.2 Publications

    GO - Molecular functioni

    1. arachidonic acid binding Source: UniProtKB
    2. enzyme activator activity Source: InterPro
    3. protein binding Source: UniProtKB
    4. protein N-terminus binding Source: UniProtKB

    GO - Biological processi

    1. arachidonic acid metabolic process Source: Reactome
    2. cellular response to calcium ion Source: UniProtKB
    3. leukotriene biosynthetic process Source: UniProtKB
    4. leukotriene metabolic process Source: Reactome
    5. leukotriene production involved in inflammatory response Source: Ensembl
    6. lipoxin metabolic process Source: Reactome
    7. lipoxygenase pathway Source: Reactome
    8. positive regulation of acute inflammatory response Source: Ensembl
    9. protein homotrimerization Source: UniProtKB
    10. small molecule metabolic process Source: Reactome

    Keywords - Biological processi

    Leukotriene biosynthesis

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000132965-MONOMER.
    ReactomeiREACT_150209. Synthesis of 5-eicosatetraenoic acids.
    REACT_150320. Synthesis of Lipoxins (LX).
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arachidonate 5-lipoxygenase-activating protein
    Alternative name(s):
    FLAP
    MK-886-binding protein
    Gene namesi
    Name:ALOX5AP
    Synonyms:FLAP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:436. ALOX5AP.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. endoplasmic reticulum Source: UniProtKB
    3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW
    5. membrane Source: UniProtKB
    6. nuclear envelope Source: UniProtKB
    7. nuclear membrane Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (PubMed:14770184), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (PubMed:17304054) ALOX5AP is not implicated in this condition.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi20 – 201V → A: Increased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi27 – 271A → V: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi30 – 301V → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi62 – 621D → A: Decreased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi66 – 661T → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi112 – 1121Y → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi113 – 1131I → A: Increased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi116 – 1161K → A: Strongly increased affinity for the inhibitor MK-591. 1 Publication
    Mutagenesisi123 – 1231F → A: Decreased affinity for the inhibitor MK-591. 1 Publication

    Organism-specific databases

    MIMi601367. phenotype.
    PharmGKBiPA47.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 161161Arachidonate 5-lipoxygenase-activating proteinPRO_0000217751Add
    BLAST

    Proteomic databases

    MaxQBiP20292.
    PaxDbiP20292.
    PRIDEiP20292.

    PTM databases

    PhosphoSiteiP20292.

    Expressioni

    Gene expression databases

    BgeeiP20292.
    CleanExiHS_ALOX5AP.
    GenevestigatoriP20292.

    Organism-specific databases

    HPAiHPA026592.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts with LTC4S and ALOX5.2 Publications

    Protein-protein interaction databases

    BioGridi106742. 4 interactions.
    IntActiP20292. 1 interaction.
    STRINGi9606.ENSP00000369858.

    Structurei

    Secondary structure

    1
    161
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 75
    Helixi10 – 2617
    Turni27 – 304
    Helixi31 – 366
    Helixi50 – 6011
    Helixi63 – 7614
    Helixi80 – 10021
    Beta strandi103 – 1064
    Helixi116 – 13823

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Q7MX-ray4.25A/B/C/D/E/F1-161[»]
    2Q7RX-ray4.00A/B/C/D/E/F1-161[»]
    ProteinModelPortaliP20292.
    SMRiP20292. Positions 1-147.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP20292.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88Lumenal1 Publication
    Topological domaini31 – 5222Cytoplasmic1 PublicationAdd
    BLAST
    Topological domaini78 – 803Lumenal1 Publication
    Topological domaini103 – 1075Cytoplasmic1 Publication
    Topological domaini129 – 16133Lumenal1 PublicationAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei108 – 1158

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 3022HelicalAdd
    BLAST
    Transmembranei53 – 7725HelicalAdd
    BLAST
    Transmembranei81 – 10222HelicalAdd
    BLAST
    Transmembranei116 – 12813HelicalAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni20 – 278Inhibitor binding
    Regioni112 – 12312Inhibitor bindingAdd
    BLAST

    Domaini

    The C-terminal part after residue 140 is mostly unstructured.1 Publication

    Sequence similaritiesi

    Belongs to the MAPEG family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG79474.
    HOGENOMiHOG000116372.
    HOVERGENiHBG107295.
    InParanoidiP20292.
    OMAiNCMDAYP.
    OrthoDBiEOG7GXPD5.
    PhylomeDBiP20292.
    TreeFamiTF105328.

    Family and domain databases

    Gene3Di1.20.120.550. 1 hit.
    InterProiIPR001446. 5_LipOase_AP.
    IPR018295. FLAP/GST2/LTC4S_CS.
    IPR023352. MAPEG-like_dom.
    IPR001129. Membr-assoc_MAPEG.
    [Graphical view]
    PfamiPF01124. MAPEG. 1 hit.
    [Graphical view]
    PRINTSiPR00488. 5LPOXGNASEAP.
    PROSITEiPS01297. FLAP_GST2_LTC4S. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P20292-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDQETVGNVV LLAIVTLISV VQNGFFAHKV EHESRTQNGR SFQRTGTLAF    50
    ERVYTANQNC VDAYPTFLAV LWSAGLLCSQ VPAAFAGLMY LFVRQKYFVG 100
    YLGERTQSTP GYIFGKRIIL FLFLMSVAGI FNYYLIFFFG SDFENYIKTI 150
    STTISPLLLI P 161
    Length:161
    Mass (Da):18,157
    Last modified:December 1, 1992 - v2
    Checksum:i2625F8081B9E1BAA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti161 – 1611P → S in CAA36441. (PubMed:2300173)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52195 mRNA. Translation: CAA36441.1.
    M63262
    , M60470, M63259, M63260 Genomic DNA. Translation: AAA35845.1.
    AY619687 Genomic DNA. Translation: AAT38104.1.
    AL512642 Genomic DNA. Translation: CAH74084.1.
    BC018538 mRNA. Translation: AAH18538.1.
    CCDSiCCDS9337.1.
    PIRiA39824.
    RefSeqiNP_001191335.1. NM_001204406.1.
    NP_001620.2. NM_001629.3.
    UniGeneiHs.507658.

    Genome annotation databases

    EnsembliENST00000380490; ENSP00000369858; ENSG00000132965.
    GeneIDi241.
    KEGGihsa:241.
    UCSCiuc001utf.2. human.

    Polymorphism databases

    DMDMi120267.

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52195 mRNA. Translation: CAA36441.1 .
    M63262
    , M60470 , M63259 , M63260 Genomic DNA. Translation: AAA35845.1 .
    AY619687 Genomic DNA. Translation: AAT38104.1 .
    AL512642 Genomic DNA. Translation: CAH74084.1 .
    BC018538 mRNA. Translation: AAH18538.1 .
    CCDSi CCDS9337.1.
    PIRi A39824.
    RefSeqi NP_001191335.1. NM_001204406.1.
    NP_001620.2. NM_001629.3.
    UniGenei Hs.507658.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2Q7M X-ray 4.25 A/B/C/D/E/F 1-161 [» ]
    2Q7R X-ray 4.00 A/B/C/D/E/F 1-161 [» ]
    ProteinModelPortali P20292.
    SMRi P20292. Positions 1-147.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106742. 4 interactions.
    IntActi P20292. 1 interaction.
    STRINGi 9606.ENSP00000369858.

    Chemistry

    BindingDBi P20292.
    ChEMBLi CHEMBL2111402.

    PTM databases

    PhosphoSitei P20292.

    Polymorphism databases

    DMDMi 120267.

    Proteomic databases

    MaxQBi P20292.
    PaxDbi P20292.
    PRIDEi P20292.

    Protocols and materials databases

    DNASUi 241.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000380490 ; ENSP00000369858 ; ENSG00000132965 .
    GeneIDi 241.
    KEGGi hsa:241.
    UCSCi uc001utf.2. human.

    Organism-specific databases

    CTDi 241.
    GeneCardsi GC13P031309.
    HGNCi HGNC:436. ALOX5AP.
    HPAi HPA026592.
    MIMi 601367. phenotype.
    603700. gene.
    neXtProti NX_P20292.
    PharmGKBi PA47.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG79474.
    HOGENOMi HOG000116372.
    HOVERGENi HBG107295.
    InParanoidi P20292.
    OMAi NCMDAYP.
    OrthoDBi EOG7GXPD5.
    PhylomeDBi P20292.
    TreeFami TF105328.

    Enzyme and pathway databases

    BioCyci MetaCyc:ENSG00000132965-MONOMER.
    Reactomei REACT_150209. Synthesis of 5-eicosatetraenoic acids.
    REACT_150320. Synthesis of Lipoxins (LX).
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Miscellaneous databases

    ChiTaRSi ALOX5AP. human.
    EvolutionaryTracei P20292.
    GeneWikii 5-lipoxygenase-activating_protein.
    GenomeRNAii 241.
    NextBioi 962.
    PROi P20292.
    SOURCEi Search...

    Gene expression databases

    Bgeei P20292.
    CleanExi HS_ALOX5AP.
    Genevestigatori P20292.

    Family and domain databases

    Gene3Di 1.20.120.550. 1 hit.
    InterProi IPR001446. 5_LipOase_AP.
    IPR018295. FLAP/GST2/LTC4S_CS.
    IPR023352. MAPEG-like_dom.
    IPR001129. Membr-assoc_MAPEG.
    [Graphical view ]
    Pfami PF01124. MAPEG. 1 hit.
    [Graphical view ]
    PRINTSi PR00488. 5LPOXGNASEAP.
    PROSITEi PS01297. FLAP_GST2_LTC4S. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis."
      Dixon R.A.F., Diehl R.E., Opas E., Rands E., Vickers P.J., Evans J.F., Gillard J.W., Miller D.K.
      Nature 343:282-284(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    2. "Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP)."
      Kennedy B.P., Diehl R.E., Boie Y., Adam M., Dixon R.A.F.
      J. Biol. Chem. 266:8511-8516(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. SeattleSNPs variation discovery resource
      Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "The DNA sequence and analysis of human chromosome 13."
      Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
      Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Tissue: Lymph.
    6. "5-lipoxygenase-activating protein is an arachidonate binding protein."
      Mancini J.A., Abramovitz M., Cox M.E., Wong E., Charleson S., Perrier H., Wang Z., Prasit P., Vickers P.J.
      FEBS Lett. 318:277-281(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    7. "5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes."
      Woods J.W., Evans J.F., Ethier D., Scott S., Vickers P.J., Hearn L., Heibein J.A., Charleson S., Singer I.I.
      J. Exp. Med. 178:1935-1946(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    8. Cited for: SUSCEPTIBILITY TO MYOCARDIAL INFARCTION, SUSCEPTIBILITY TO ISCHSTR.
    9. "No association of polymorphisms in the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a large central European population."
      Koch W., Hoppmann P., Mueller J.C., Schomig A., Kastrati A.
      Genet. Med. 9:123-129(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: LACK OF ASSOCIATION WITH MYOCARDIAL INFARCTION.
    10. "Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein."
      Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M., Hammarstroem S.
      Biochem. Biophys. Res. Commun. 381:518-522(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LTC4S AND ALOX5, SUBCELLULAR LOCATION.
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEXES WITH LEUKOTRIENE BIOSYNTHESIS INHIBITOR MK-591, TOPOLOGY, SUBUNIT, MUTAGENESIS OF VAL-20; ALA-27; VAL-30; ASP-62; THR-66; TYR-112; ILE-113; LYS-116 AND PHE-123, DOMAIN.

    Entry informationi

    Entry nameiAL5AP_HUMAN
    AccessioniPrimary (citable) accession number: P20292
    Secondary accession number(s): Q5VV04
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1991
    Last sequence update: December 1, 1992
    Last modified: October 1, 2014
    This is version 130 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3