5-lipoxygenase-activating protein

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.^[4][5]

ALOX5AP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Q7R, 2Q7M
Identifiers
Aliases	ALOX5AP, FLAP, arachidonate 5-lipoxygenase activating protein
External IDs	OMIM: 603700; MGI: 107505; HomoloGene: 1231; GeneCards: ALOX5AP; OMA:ALOX5AP - orthologs
Gene location (Mouse) Chr. Chromosome 5 (mouse)[1] Band 5|5 G3 Start 149,201,577 bp[1] End 149,224,963 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood trabecular bone bone marrow right lung bone marrow cells monocyte upper lobe of left lung spleen lower lobe of lung periodontal fiber Top expressed in granulocyte stroma of bone marrow tibiofemoral joint blood right lung lobe ankle interventricular septum carotid body spleen sciatic nerve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glutathione transferase activity protein N-terminus binding leukotriene-C4 synthase activity glutathione peroxidase activity protein binding arachidonic acid binding enzyme activator activity Cellular component integral component of membrane nuclear membrane endoplasmic reticulum membrane membrane nuclear envelope endoplasmic reticulum nucleus Biological process cellular response to calcium ion leukotriene metabolic process positive regulation of catalytic activity protein homotrimerization lipoxygenase pathway leukotriene biosynthetic process lipoxin metabolic process cellular oxidant detoxification lipoxin biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 241 11690 Ensembl n/a ENSMUSG00000060063 UniProt P20292 P30355 RefSeq (mRNA) NM_001204406 NM_001629 NM_009663 NM_001308462 RefSeq (protein) NP_001191335 NP_001620 NP_001295391 NP_033793 Location (UCSC) n/a Chr 5: 149.2 – 149.22 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.^[6][7] 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. ^{[citation needed]} FLAP structure consists of 4 transmembrane alpha helices, but they are found in trimer forming a barrel. The barrel is about 60 Å high and 36 Å wide.^[8]

Clinical significance

Leukotrienes, which require the FLAP protein to be synthesized, 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.^[9] 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.^[8][10]

Inhibitors

• AM-679^[11]
• MK-886^[12]
• Veliflapon (BAY X1005)