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This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
ALOX5 (Arachidonate 5-Lipoxygenase) is a Protein Coding gene. Diseases associated with ALOX5 include Asthma and Atherosclerosis Susceptibility. Among its related pathways are Folate Metabolism and Eicosanoid Synthesis. Gene Ontology (GO) annotations related to this gene include iron ion binding and arachidonate 5-lipoxygenase activity. An important paralog of this gene is ALOX15B.
Lipoxygenases (LOXs) are a family of non-heme iron dioxygenases that are involved in the production and metabolism of fatty acid hydroperoxidases. There are six lipoxygenase isozymes; 5-LOX, 12R-LOX, 12S-LOX, 15-LOX-1, 15-LOX-2 and E-LOX.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004051 | arachidonate 5-lipoxygenase activity | TAS | -- |
GO:0005506 | iron ion binding | IEA,IDA | 21233389 |
GO:0005515 | protein binding | IEA,IPI | 7929073 |
GO:0016491 | oxidoreductase activity | IEA | -- |
GO:0016702 | oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen | IEA,IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | HDA | 22664934 |
GO:0005634 | nucleus | IEA | -- |
GO:0005635 | nuclear envelope | IDA,TAS | -- |
GO:0005641 | nuclear envelope lumen | IDA | 8245774 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Arachidonic acid metabolism | ||
2 | Metabolism |
.40
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|
3 | Innate Immune System |
.61
|
|
4 | HETE and HPETE biosynthesis and metabolism |
HETE and HPETE biosynthesis and metabolism
-
|
|
5 | aspirin triggered resolvin D biosynthesis |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001937 | negative regulation of endothelial cell proliferation | ISS | -- |
GO:0002232 | leukocyte chemotaxis involved in inflammatory response | IMP | 17114001 |
GO:0002523 | leukocyte migration involved in inflammatory response | ISS | -- |
GO:0002540 | leukotriene production involved in inflammatory response | IEA | -- |
GO:0006691 | leukotriene metabolic process | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Zileuton | Approved, Investigational, Withdrawn | Pharma | Inhibitor, Inhibition, Target, inhibitor | 5-lipoxygenase (5-LOX) inhibitor, orally active | 20 | |
Montelukast | Approved | Pharma | Antagonist, Target, other/unknown | 302 | ||
Balsalazide | Approved, Investigational | Pharma | Target, inhibitor | 8 | ||
Meclofenamic acid | Approved, Vet_approved | Pharma | Target, inhibitor | 2 | ||
Mesalazine | Approved | Pharma | Target, inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
5-Hpete |
|
74581-83-2 | ||||
4'-Hydroxydiclofenac |
|
64118-84-9 | ||||
5(S)-Hydroperoxyeicosatetraenoic acid |
|
71774-08-8 |
|
|||
9(S)-HPODE |
|
|
||||
Hydroxyzileuton |
|
|
Compound | Action | Cas Number |
---|---|---|
2-TEDC | 5-, 12-, 15-Lipoxygenase inhibitor | 132465-10-2 |
Baicalein | 5- and 12-Lipoxygenase inhibitor | 491-67-8 |
BAY-X 1005 | Orally active 5-lipoxygenase activating protein (FLAP) inhibitor | 128253-31-6 |
BW-B 70C | 5-Lipoxygenase inhibitor | 134470-38-5 |
MK 886 | Inhibitor of 5-lipoxygenase-activating protein (FLAP) | 118414-82-7 |
Compound | Action | Cas Number |
---|---|---|
2-TEDC | 132465-10-2 | |
BAY-X 1005 | Potent FLAP inhibitor | 128253-31-6 |
Butein | Protein kinase inhibitor | 487-52-5 |
BW-B 70C | 5-Lipoxygenase inhibitor,potent and selective | 134470-38-5 |
Malotilate | Tyrosine kinase inhibitors | 59937-28-9 |
MK 886 | 118414-82-7 | |
PD 146176 | 4079-26-9 | |
U-73122 | 112648-68-7 | |
Zileuton | 5-lipoxygenase (5-LOX) inhibitor, orally active | 111406-87-2 |
Zileuton sodium | 5-lipoxygenase and leukotrienes inhibitor | 118569-21-4 |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ALOX5 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | ALOX5 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | ALOX5 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | ALOX5 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | ALOX5 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Alox5 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Alox5 30 |
|
||
Chicken (Gallus gallus) |
Aves | ALOX5 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | ALOX5 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | alox5 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | alox5a 30 31 |
|
OneToMany | |
alox5b.3 31 |
|
OneToMany | |||
ALOX5 (1 of 4) 31 |
|
OneToMany | |||
alox5b.2 31 |
|
OneToMany | |||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | LOX5 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os03g0699700 30 |
|
||
Corn (Zea mays) |
Liliopsida | Zm.14487 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany | |
CSA.6148 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 10 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
713947 | Benign: not provided | 45,382,650(+) | C/T | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT | |
738796 | Likely Benign: not provided | 45,382,569(+) | C/T | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT | |
741995 | Likely Benign: not provided | 45,395,902(+) | C/T | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT | |
760574 | Likely Benign: not provided | 45,382,542(+) | C/T | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT | |
770765 | Likely Benign: not provided | 45,428,638(+) | G/A | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2513283 | CNV | deletion | 19546169 |
esv2567160 | CNV | deletion | 19546169 |
esv3891797 | CNV | gain | 25118596 |
nsv1043536 | CNV | gain | 25217958 |
nsv466910 | CNV | loss | 19166990 |
nsv550715 | CNV | loss | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
asthma |
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atherosclerosis susceptibility |
|
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allergic rhinitis |
|
|
arthus reaction |
|
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paranasal sinus disease |
|
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