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Arachidonate 5-lipoxygenase-activating protein; FLAP; MK-886-binding protein (ALOX5AP, FLAP)
Function:
- required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase)
- anchors ALOX5 to the membrane
- binds arachidonic acid, & could play an essential role in the transfer of arachidonic acid to ALOX5
- after release by phospholipase, arachidonic acid is translocated to bind the integral perinuclear membrane protein, FLAP
- FLAP appears to activate Ca+2-dependent 5-lipoxygenase activty
- binds to MK-886, a compound that blocks the biosynthesis of leukotrienes
- Inhibited by DG-013 [4]
- interacts with LTC4S & ALOX5
Structure:
- homotrimer
- the C-terminal part after residue 140 is mostly unstructured
- belongs to the MAPEG family
Compartment:
- nuclear membrane
- endoplasmic reticulum membrane
Pathology:
- genetic variations in ALOX5AP may be a cause of susceptibility to ischemic stroke
- haplotypes hapA & hapB are associated with susceptibility to myocardial infarction
Related
5-lipoxygenase (arachidonate-5-lipoxygenase, ALOX5)
DG-031 (formerly Bay x 1005)
General
nuclear protein
transmembrane 4e protein
Properties
SIZE: entity length = 161 aa
MW = 18 kD
COMPARTMENT: cell nucleus
endoplasmic reticulum
MOTIF: exoplasmic domain {1-8}
transmembrane domain {9-30}
MOTIF: Inhibitor binding {20-27}
cytoplasmic loop {31-52}
transmembrane domain {53-77}
exoplasmic loop {78-80}
transmembrane domain {81-102}
cytoplasmic loop {103-107}
transmembrane domain {108-128}
MOTIF: In membrane {108-115}
Inhibitor binding
NAME: Inhibitor binding
SITE: 112-123
exoplasmic domain {129-161}
Database Correlations
OMIM correlations
UniProt P20292
Pfam PF01124
Entrez Gene 241
Kegg hsa:241
References
- UniProt :accession P20292
- SeattleSNPs
http://pga.gs.washington.edu/data/alox5ap/
- Harrison's Principles of Internal Medicine, 14th ed.
Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1861
- Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D,
Zink F, Andresdottir M, Manolescu A, Arnar DO, Andersen K,
Sigurdsson A, Thorgeirsson G, Jonsson A, Agnarsson U,
Bjornsdottir H, Gottskalksson G, Einarsson A, Gudmundsdottir H,
Adalsteinsdottir AE, Gudmundsson K, Kristjansson K, Hardarson T,
Kristinsson A, Topol EJ, Gulcher J, Kong A, Gurney M,
Thorgeirsson G, Stefansson K.
Effects of a 5-lipoxygenase-activating protein inhibitor on
biomarkers associated with risk of myocardial infarction:
a randomized trial.
JAMA. 2005 May 11;293(18):2245-56.
PMID: 15886380