5-lipoxygenase-activating protein

Arachidonate 5-lipoxygenase-activating protein
250px Crystallographic structure of the inhibitor-bound human 5-lipoxygenase-activating protein.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2Q7M, 2Q7R
Identifiers
Symbols	ALOX5AP ; FLAP
External IDs	OMIM: 603700 MGI: 107505 HomoloGene: 1231 ChEMBL: 4550 GeneCards: ALOX5AP Gene
Gene ontology Molecular function • glutathione transferase activity • leukotriene-C4 synthase activity • glutathione peroxidase activity • protein binding • enzyme activator activity • protein N-terminus binding • arachidonic acid binding Cellular component • nuclear envelope • endoplasmic reticulum • endoplasmic reticulum membrane • membrane • integral component of membrane • nuclear membrane Biological process • leukotriene metabolic process • arachidonic acid metabolic process • leukotriene biosynthetic process • lipoxygenase pathway • positive regulation of catalytic activity • small molecule metabolic process • protein homotrimerization • cellular response to calcium ion • lipoxin metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	241	11690
Ensembl	ENSG00000132965	ENSMUSG00000060063
UniProt	P20292	P30355
RefSeq (mRNA)	NM_001204406	NM_001308462
RefSeq (protein)	NP_001191335	NP_001295391
Location (UCSC)	Chr 13: 30.71 – 30.76 Mb	Chr 5: 149.27 – 149.29 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.

Function

FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes. 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.

Clinical significance

Gene polymorphisms in FLAP are suspected of playing a role in Alzheimer's disease. 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.

Inhibitors

• AM-679

External links

• 5-lipoxygenase-activating protein at the US National Library of Medicine Medical Subject Headings (MeSH)