5-lipoxygenase-activating protein

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ALOX5AP
5lip.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesALOX5AP, FLAP, arachidonate 5-lipoxygenase activating protein
External IDsOMIM: 603700 MGI: 107505 HomoloGene: 1231 GeneCards: ALOX5AP
Gene location (Human)
Chromosome 13 (human)
Chr.Chromosome 13 (human)[1]
Chromosome 13 (human)
Genomic location for ALOX5AP
Genomic location for ALOX5AP
Band13q12.3Start30,713,478 bp[1]
End30,764,426 bp[1]
RNA expression pattern
PBB GE PNPLA6 203718 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001204406
NM_001629

NM_009663
NM_001308462

RefSeq (protein)

NP_001191335
NP_001620

NP_001295391
NP_033793

Location (UCSC)Chr 13: 30.71 – 30.76 MbChr 5: 149.26 – 149.29 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene.[5][6]

Function[edit]

FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and specialized pro-resolving mediators of the lipoxin and resolvin classes.[7][8] It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP structure consist of 4 transmembrane alpha helices, but they are found in 3’s( trimer) forming a barrel. The barrel is about 60 A high and 36 A wide.[9]

Clinical significance[edit]

Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke. The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.[9]

Inhibitors[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132965 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060063 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kennedy BP, Diehl RE, Boie Y, Adam M, Dixon RA (May 1991). "Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP)". The Journal of Biological Chemistry. 266 (13): 8511–6. PMID 1673682.
  6. ^ Yandava CN, Kennedy BP, Pillari A, Duncan AM, Drazen JM (February 1999). "Cytogenetic and radiation hybrid mapping of human arachidonate 5-lipoxygenase-activating protein (ALOX5AP) to chromosome 13q12". Genomics. 56 (1): 131–3. doi:10.1006/geno.1998.5651. PMID 10036194.
  7. ^ Peters-Golden M, Brock TG (2003). "5-lipoxygenase and FLAP". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 69 (2–3): 99–109. doi:10.1016/S0952-3278(03)00070-X. PMID 12895592.
  8. ^ Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMC 4315926. PMID 25359497.
  9. ^ a b PDB: 2q7r​;Ferguson AD, McKeever BM, Xu S, Wisniewski D, Miller DK, Yamin TT, Spencer RH, Chu L, Ujjainwalla F, Cunningham BR, Evans JF, Becker JW (July 2007). "Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein". Science. 317 (5837): 510–2. doi:10.1126/science.1144346. PMID 17600184.
  10. ^ Musiyenko A, Correa L, Stock N, Hutchinson JH, Lorrain DS, Bain G, Evans JF, Barik S (November 2009). "A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation in the respiratory syncytial virus-infected mouse eye". Clinical and Vaccine Immunology. 16 (11): 1654–9. doi:10.1128/CVI.00220-09. PMC 2772391. PMID 19759251.

Further reading[edit]

External links[edit]