5-lipoxygenase-activating protein

arachidonate 5-lipoxygenase-activating protein

Crystallographic structure of the inhibitor-bound human 5-lipoxygenase-activating protein.^[1]

Available structures
PDB	2q7m, 2q7r

Identifiers

Symbols

ALOX5AP; FLAP

External IDs

OMIM: 603700 MGI: 107505 HomoloGene: 1231 GeneCards: ALOX5AP Gene

Gene Ontology
Molecular function	• protein N-terminus binding • enzyme activator activity • binding • arachidonic acid binding
Cellular component	• membrane • nuclear membrane • nucleus • endoplasmic reticulum • integral to membrane
Biological process	• leukotriene metabolic process • leukotriene biosynthetic process • protein homotrimerization • inflammatory response
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 13:
30.21 – 30.24 Mb

Chr 5:
150.08 – 150.1 Mb

PubMed search

[1]

[2]

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.^[2]^[3]

1 Function
2 Clinical significance
3 Inhibitors
4 References
5 Further reading
6 External links

Function

FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes.^[4] 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.^[1]

Clinical significance

Gene polymorphisms in FLAP are suspected of playing a role in Alzheimer's disease.^[5] 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.^[1]

Inhibitors

AM-679^[6]

References

^ ^a ^b ^c 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.
^ 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)". J. Biol. Chem. 266 (13): 8511–6. PMID 1673682.
^ 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.
^ Peters-Golden M, Brock TG (2003). "5-lipoxygenase and FLAP". Prostaglandins Leukot Essent Fatty Acids 69 (2-3): 99–109. doi:10.1016/S0952-3278(03)00070-X. PMID 12895592.
^ Manev H, Manev R (2006). "5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease". Med Hypotheses 66 (3): 501–3. doi:10.1016/j.mehy.2005.09.031. PMID 16278051.
^ Musiyenko, A.; Correa, L.; Stock, N.; Hutchinson, J. H.; Lorrain, D. S.; Bain, G.; Evans, J. F.; Barik, S. (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. doi:10.1128/CVI.00220-09. PMC 2772391. PMID 19759251. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2772391. edit

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