ALOX5 Gene (Protein Coding)

Arachidonate 5-Lipoxygenase

GC10P045374
GIFtS:
50
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-tr... See more...

Aliases for ALOX5 Gene

Aliases for ALOX5 Gene

  • Arachidonate 5-Lipoxygenase 2 3 4 5
  • Polyunsaturated Fatty Acid 5-Lipoxygenase 3 4
  • EC 1.13.11.34 4 50
  • 5-LOX 2 3
  • 5-LO 3 4
  • LOG5 3 4
  • Arachidonic Acid 5-Lipoxygenase 3
  • Leukotriene A4 Synthase 3
  • 5-Lipoxygenase 4
  • EC 1.13.11.- 4
  • EC 1.13.11 50
  • LOX-5 3
  • ALOX5 5
  • 5LPG 3

External Ids for ALOX5 Gene

Previous GeneCards Identifiers for ALOX5 Gene

  • GC10P045171
  • GC10P045338
  • GC10P045644
  • GC10P045153
  • GC10P045189
  • GC10P045869
  • GC10P042394

Summaries for ALOX5 Gene

Entrez Gene Summary for ALOX5 Gene

  • 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]

GeneCards Summary for ALOX5 Gene

ALOX5 (Arachidonate 5-Lipoxygenase) is a Protein Coding gene. Diseases associated with ALOX5 include Asthma and Exercise-Induced Bronchoconstriction. Among its related pathways are HETE and HPETE biosynthesis and metabolism and Arachidonic acid metabolism. 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.

UniProtKB/Swiss-Prot Summary for ALOX5 Gene

  • Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). Also may play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).

Tocris Summary for ALOX5 Gene

  • 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.

Gene Wiki entry for ALOX5 Gene

PharmGKB "VIP" Summary for ALOX5 Gene

Additional gene information for ALOX5 Gene

No data available for CIViC Summary , Rfam classification and piRNA Summary for ALOX5 Gene

Genomics for ALOX5 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for ALOX5 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ALOX5 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ALOX5

Top Transcription factor binding sites by QIAGEN in the ALOX5 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • Egr-1
  • GR
  • GR-alpha
  • p53
  • Sp1

Genomic Locations for ALOX5 Gene

Latest Assembly
chr10:45,374,176-45,446,121
(GRCh38/hg38)
Size:
71,946 bases
Orientation:
Plus strand

Previous Assembly
chr10:45,869,664-45,941,565
(GRCh37/hg19 by Entrez Gene)
Size:
71,902 bases
Orientation:
Plus strand

chr10:45,869,661-45,941,561
(GRCh37/hg19 by Ensembl)
Size:
71,901 bases
Orientation:
Plus strand

Alternative Locations (GRCh38/hg38)

  • chr10(ALT_REF_LOCI_1):215,047-286,948 (+)

Genomic View for ALOX5 Gene

Genes around ALOX5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ALOX5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ALOX5 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ALOX5 Gene

Proteins for ALOX5 Gene

Products:

  1. Antibodies for research
  2. Protein products for research
  3. Assay products for research

  • Protein details for ALOX5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P09917-LOX5_HUMAN
    Recommended name:
    Polyunsaturated fatty acid 5-lipoxygenase
    Protein Accession:
    P09917
    Secondary Accessions:
    • B7ZLS0
    • E5FPY5
    • E5FPY7
    • E5FPY8
    • Q5JQ14

    Protein attributes for ALOX5 Gene

    Size:
    674 amino acids
    Molecular mass:
    77983 Da
    Cofactor:
    Name=Fe cation; Xref=ChEBI:CHEBI:24875;
    Quaternary structure:
    • Homodimer (PubMed:22516296, PubMed:21233389). Interacts with ALOX5AP and LTC4S (PubMed:19233132). Interacts with COTL1, the interaction is required for stability and efficient catalytic activity (PubMed:19807693). Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (PubMed:21200133). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1 (PubMed:19022417).

    Three dimensional structures from OCA and Proteopedia for ALOX5 Gene

    Alternative splice isoforms for ALOX5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ALOX5 Gene

Protein Expression for ALOX5 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for ALOX5 Gene

P09917:
  • NHWQEDLMFGYQFLNGCNPVLI
  • QFLAAPICLLYKNLANKIVPIAIQLNQ
  • SLCFPEAIKARGM
  • YRDDGLLVW
  • TAKGVVTIEQIV
  • HAAVNFGQY
  • WVRSSDF
  • KLPVTTEMVECSLER
  • NPVLIRRC
  • ELLDGIDANKTDPCT
  • GLFDKANATGGGGHVQMVQRA
  • FGYQFLNG
  • VIFTASAQHAAVNF
  • TLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKP

Post-translational modifications for ALOX5 Gene

  • Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid (PubMed:11844797, PubMed:18978352). Phosphorylation on Ser-524 by PKA has an inhibitory effect (PubMed:15280375). Phosphorylation on Ser-272 prevents export from the nucleus (PubMed:11844797, PubMed:18978352). Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2 (PubMed:26210919).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ALOX5 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for ALOX5 Gene

Gene Families for ALOX5 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

Protein Domains for ALOX5 Gene

InterPro:
Blocks:
  • Lipoxygenase, LH2 domain
  • Lipoxygenase
  • Mammalian lipoxygenase signature

Suggested Antigen Peptide Sequences for ALOX5 Gene

GenScript: Design optimal peptide antigens:
  • Arachidonic 5-lipoxygenase delta-10-13 isoform (E5FPY5_HUMAN)
  • Arachidonic 5-lipoxygenase alpha-10 isoform (E5FPY7_HUMAN)
  • Arachidonic 5-lipoxygenase delta-p10 isoform (E5FPY8_HUMAN)
  • Arachidonate 5-lipoxygenase (LOX5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P09917

UniProtKB/Swiss-Prot:

LOX5_HUMAN :
  • Belongs to the lipoxygenase family.
Family:
  • Belongs to the lipoxygenase family.
genes like me logo Genes that share domains with ALOX5: view

Function for ALOX5 Gene

Products:

  1. Animal Models for research
  2. CRISPR products for research
  3. miRNA products for research
  4. Inhibitory RNAs for research
  5. Clone products for research
  6. Cell Lines for research

Molecular function for ALOX5 Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). Also may play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = H2O + leukotriene A4; Xref=Rhea:RHEA:32307, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57463; EC=1.13.11.34; Evidence={ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:21233389};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate; Xref=Rhea:RHEA:48860, ChEBI:CHEBI:15379, ChEBI:CHEBI:90825, ChEBI:CHEBI:90826; Evidence={ECO:0000269|PubMed:17114001};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; Xref=Rhea:RHEA:51968, ChEBI:CHEBI:15379, ChEBI:CHEBI:90818, ChEBI:CHEBI:132218; Evidence={ECO:0000269|PubMed:21206090};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; Xref=Rhea:RHEA:50204, ChEBI:CHEBI:15379, ChEBI:CHEBI:132083, ChEBI:CHEBI:132091; Evidence={ECO:0000269|PubMed:21206090};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O; Xref=Rhea:RHEA:39107, ChEBI:CHEBI:15377, ChEBI:CHEBI:132091, ChEBI:CHEBI:134661; Evidence={ECO:0000269|PubMed:21206090};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O; Xref=Rhea:RHEA:50268, ChEBI:CHEBI:15377, ChEBI:CHEBI:132218, ChEBI:CHEBI:132219; Evidence={ECO:0000269|PubMed:21206090, ECO:0000305|PubMed:17114001};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O; Xref=Rhea:RHEA:50844, ChEBI:CHEBI:15377, ChEBI:CHEBI:90826, ChEBI:CHEBI:133812; Evidence={ECO:0000269|PubMed:17114001};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:17485, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57450; Evidence={ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:22516296, ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + O2 = (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:48624, ChEBI:CHEBI:15379, ChEBI:CHEBI:57409, ChEBI:CHEBI:131564; Evidence={ECO:0000269|PubMed:31664810, ECO:0000269|PubMed:8615788};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = H2O + leukotriene A4; Xref=Rhea:RHEA:17961, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:57463; Evidence={ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:8631361};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:38675, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75322; Evidence={ECO:0000269|PubMed:23246375};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:10428, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57444; Evidence={ECO:0000269|PubMed:23246375};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z)-eicosadienoate + O2 = (5S)-hydroperoxy-(6E,8Z)-eicosadienoate; Xref=Rhea:RHEA:62644, ChEBI:CHEBI:15379, ChEBI:CHEBI:145835, ChEBI:CHEBI:145836; Evidence={ECO:0000305|PubMed:8631361};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(12S)-hydroxy-(6E,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:62648, ChEBI:CHEBI:15379, ChEBI:CHEBI:90680, ChEBI:CHEBI:145837; Evidence={ECO:0000305|PubMed:8631361};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate; Xref=Rhea:RHEA:62600, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562, ChEBI:CHEBI:145815; Evidence={ECO:0000269|PubMed:31664810};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate; Xref=Rhea:RHEA:41332, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, ChEBI:CHEBI:78048; Evidence={ECO:0000269|PubMed:32404334};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate; Xref=Rhea:RHEA:64668, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, ChEBI:CHEBI:156049; Evidence={ECO:0000269|PubMed:32404334, ECO:0000305|PubMed:31664810};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate; Xref=Rhea:RHEA:50840, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, ChEBI:CHEBI:133795; Evidence={ECO:0000269|PubMed:32404334};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=13 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate {ECO:0000269|PubMed:8631361}; KM=11 uM for arachidonic acid {ECO:0000269|PubMed:22516296}; KM=1.9 uM for arachidonic acid {ECO:0000269|PubMed:24893149}; KM=14 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate {ECO:0000269|PubMed:24893149}; KM=5.3 uM for arachidonic acid (in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; KM=19 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; KM=1.6 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ from arachidonic acid) {ECO:0000269|PubMed:24893149}; KM=4.5 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ from arachidonic acid in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; Vmax=1 umol/min/mg enzyme toward arachidonic acid {ECO:0000269|PubMed:24893149}; Vmax=0.33 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate {ECO:0000269|PubMed:24893149}; Vmax=4.9 umol/min/mg enzyme toward arachidonic acid (in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; Vmax=1.6 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; Vmax=0.1 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ from arachidonic acid) {ECO:0000269|PubMed:24893149}; Vmax=2 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ from arachidonic acid in the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149};
UniProtKB/Swiss-Prot EnzymeRegulation:
Undergoes a sequential loss of the oxygenase and pseudoperoxidase activities which is dependent on the structural characteristics of the substrate for the reaction, on oxygen concentration and on exposure to phospholipids and calcium (PubMed:8631361). 15-HETE and other 15-mono-hydroxyeicosanoids exhibit the highest inhibitory potencies in their capability of suppressing 5-lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well as octadecanoids, are modest or poor inhibitors (PubMed:8615788). The formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid (PubMed:8615788). Arachidonate 5-lipoxygenase and leukotriene A4 synthase activities are allosterically increased by ATP (PubMed:24893149).
GENATLAS Biochemistry:
arachidonate-5-lipoxygenase,lipid peroxidating enzyme implicated in the pathogenesis of inflammatory disorders as well as membrane remodeling,carcinogenesis,atheroma and asthma formation,involved in leukotriene metabolism

Enzyme Numbers (IUBMB) for ALOX5 Gene

Phenotypes From GWAS Catalog for ALOX5 Gene

Gene Ontology (GO) - Molecular Function for ALOX5 Gene

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
genes like me logo Genes that share ontologies with ALOX5: view
genes like me logo Genes that share phenotypes with ALOX5: view

Human Phenotype Ontology for ALOX5 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ALOX5 Gene

MGI Knock Outs for ALOX5:

Animal Models for research

miRNA for ALOX5 Gene

miRTarBase miRNAs that target ALOX5

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ALOX5

No data available for Transcription Factor Targets and HOMER Transcription for ALOX5 Gene

Localization for ALOX5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ALOX5 Gene

Cytoplasm. Nucleus matrix. Nucleus membrane. Peripheral membrane protein. Cytoplasm, perinuclear region. Cytoplasm, cytosol. Nucleus envelope. Nucleus intermembrane space. Note=Shuttles between cytoplasm and nucleus (PubMed:19233132). Found exclusively in the nucleus, when phosphorylated on Ser-272 (PubMed:18978352). Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association (PubMed:19233132, PubMed:3118366, PubMed:8245774, PubMed:16275640). {ECO:0000269 PubMed:16275640, ECO:0000269 PubMed:18978352, ECO:0000269 PubMed:19233132, ECO:0000269 PubMed:3118366, ECO:0000269 PubMed:8245774}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ALOX5 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ALOX5 Gene

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 TAS --
GO:0005641 nuclear envelope lumen IEA,IDA 8245774
genes like me logo Genes that share ontologies with ALOX5: view

Pathways & Interactions for ALOX5 Gene

genes like me logo Genes that share pathways with ALOX5: view

Pathways by source for ALOX5 Gene

1 PharmGKB pathway for ALOX5 Gene
1 GeneGo (Thomson Reuters) pathway for ALOX5 Gene
  • HETE and HPETE biosynthesis and metabolism
1 Qiagen pathway for ALOX5 Gene
  • all-trans-Retinoic Acid Signaling in Brain
2 Cell Signaling Technology pathways for ALOX5 Gene

UniProtKB/Swiss-Prot P09917-LOX5_HUMAN

  • Pathway: Lipid metabolism; leukotriene A4 biosynthesis.

SIGNOR curated interactions for ALOX5 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ALOX5 Gene

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 --
genes like me logo Genes that share ontologies with ALOX5: view

Drugs & Compounds for ALOX5 Gene

Products:

  1. Drug products for research

(111) Drugs for ALOX5 Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zileuton Approved, Investigational, Withdrawn Pharma Inhibitor, Inhibition, Target 5-lipoxygenase (5-LOX) inhibitor, orally active 20
Montelukast Approved Pharma Target, other/unknown 321
Balsalazide Approved, Investigational Pharma Target, inhibitor 9
Meclofenamic acid Approved, Vet_approved Pharma Target, inhibitor 2
Mesalazine Approved Pharma Target, inhibitor 0

(81) Additional Compounds for ALOX5 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5-Hpete
  • (6E,8Z,11Z,14Z)-5-Hydroperoxyicosatetraenoic acid
  • 5-Hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid
  • 5-Hydroperoxy-(6E,8Z,11Z,14Z)-icosatetraenoic acid
  • 6,8,11,14-Eicosatetraenoic acid 5-hydroperoxide
  • Arachidonic acid 5-hydroperoxide
 74581-83-2
4'-Hydroxydiclofenac
  • (O-(2,6-Dichloro-4-hydroxyanilino)phenyl)acetic acid
  • 4'-Hydroxy diclofenac
  • 4'-OH DCF
  • (O-(2,6-Dichloro-4-hydroxyanilino)phenyl)acetate
  • {2-[(2,6-dichloro-4-hydroxyphenyl)amino]phenyl}acetic acid
 64118-84-9
5(S)-Hydroperoxyeicosatetraenoic acid
  • (5S,6E,8Z,11Z,14Z)-5-Hydroperoxyeicosa-6,8,11,14-tetraenoic acid
  • (5S,6E,8Z,11Z,14Z)-5-Hydroperoxyicosa-6,8,11,14-tetraenoate
  • (6E,8Z,11Z,14Z)-(5S)-5-Hydroperoxyeicosa-6,8,11,14-tetraenoate
  • (6E,8Z,11Z,14Z)-(5S)-5-Hydroperoxyeicosa-6,8,11,14-tetraenoic acid
  • (S)-5-HPETE
 71774-08-8
9(S)-HPODE
  • (10E,12Z)-9-Hydroperoxyoctadeca-10,12-dienoate
Hydroxyzileuton

(5) Tocris Compounds for ALOX5 Gene

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

(10) ApexBio Compounds for ALOX5 Gene

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
genes like me logo Genes that share compounds with ALOX5: view

Drug products for research

Transcripts for ALOX5 Gene

Products:

  1. CRISPR products for research
  2. miRNA products for research
  3. Inhibitory RNAs for research
  4. Clone products for research

mRNA/cDNA for ALOX5 Gene

5 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ALOX5

Alternative Splicing Database (ASD) splice patterns (SP) for ALOX5 Gene

No ASD Table

Relevant External Links for ALOX5 Gene

GeneLoc Exon Structure for
ALOX5

Expression for ALOX5 Gene

Products:

  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ALOX5 Gene

mRNA expression in normal human tissues for ALOX5 Gene
mRNA expression by GTEx for ALOX5 GenemRNA expression by BioGPS for ALOX5 Gene

mRNA differential expression in normal tissues according to GTEx for ALOX5 Gene

This gene is overexpressed in Whole Blood (x28.6).

Protein differential expression in normal tissues from HIPED for ALOX5 Gene

This gene is overexpressed in Lymph node (23.1) and Peripheral blood mononuclear cells (17.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ALOX5 Gene



Protein tissue co-expression partners for ALOX5 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ALOX5

SOURCE GeneReport for Unigene cluster for ALOX5 Gene:

Hs.89499

Evidence on tissue expression from TISSUES for ALOX5 Gene

  • Nervous system(4.6)
  • Blood(3.3)
  • Intestine(3.1)
  • Lung(3)
  • Bone marrow(3)
  • Spleen(2.9)
  • Heart(2.8)
  • Lymph node(2.7)
  • Pancreas(2.5)
  • Stomach(2.5)
  • Liver(2.4)
  • Skin(2.3)
  • Muscle(2.2)
  • Kidney(2.2)
genes like me logo Genes that share expression patterns with ALOX5: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ALOX5 Gene

Orthologs for ALOX5 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ALOX5 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia ALOX5 29 30
  • 97.42 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia ALOX5 30
  • 92 (a)
 OneToOne
Dog
(Canis familiaris)
 Mammalia ALOX5 29 30
  • 90.16 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia ALOX5 29 30
  • 90.11 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia ALOX5 30
  • 90 (a)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Alox5 29 16 30
  • 87.88 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Alox5 29
  • 86.29 (n)
Chicken
(Gallus gallus)
 Aves ALOX5 29 30
  • 76.85 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia ALOX5 30
  • 80 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia alox5 29
  • 71.07 (n)
Zebrafish
(Danio rerio)
 Actinopterygii alox5a 29 30
  • 70.18 (n)
 OneToMany
alox5b.3 30
  • 59 (a)
 OneToMany
ALOX5 (1 of 4) 30
  • 58 (a)
 OneToMany
alox5b.2 30
  • 57 (a)
 OneToMany
Thale Cress
(Arabidopsis thaliana)
 eudicotyledons LOX5 29
  • 44.58 (n)
Rice
(Oryza sativa)
 Liliopsida Os03g0699700 29
  • 46.5 (n)
Corn
(Zea mays)
 Liliopsida Zm.14487 29
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 30
  • 38 (a)
 ManyToMany
CSA.6148 30
  • 35 (a)
 ManyToMany
-- 30
  • 32 (a)
 ManyToMany
-- 30
  • 31 (a)
 ManyToMany
Species where no ortholog for ALOX5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ALOX5 Gene

ENSEMBL:
Gene Tree for ALOX5 (if available)
TreeFam:
Gene Tree for ALOX5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ALOX5: view image
Alliance of Genome Resources:
Additional Orthologs for ALOX5

Paralogs for ALOX5 Gene

Paralogs for ALOX5 Gene

(5) SIMAP similar genes for ALOX5 Gene using alignment to 2 proteins:

  • LOX5_HUMAN
  • I0CLG0_HUMAN
genes like me logo Genes that share paralogs with ALOX5: view

Variants for ALOX5 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ALOX5 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs1177150106 Likely Benign: not provided 45,428,773(+) C/T
NM_000698.5(ALOX5):c.981+9C>T 		INTRON
rs146362560 Not Provided: not provided 45,440,444(+) G/A
NM_000698.5(ALOX5):c.996G>A (p.Pro332=) 		SYNONYMOUS
rs150281723 Benign: not provided 45,382,650(+) C/T
NM_000698.5(ALOX5):c.318C>T (p.Gly106=) 		SYNONYMOUS_VARIANT,FIVE_PRIME_UTR
rs179363899 Not Provided: not provided 45,443,004(+) C/T
NM_000698.5(ALOX5):c.1273-34C>T 		INTRON
rs182401295 Likely Benign: not provided 45,382,569(+) C/T
NM_000698.5(ALOX5):c.237C>T (p.Asp79=) 		SYNONYMOUS_VARIANT,FIVE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ALOX5 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ALOX5 Gene

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

Variation tolerance for ALOX5 Gene

Residual Variation Intolerance Score: 8.22% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.03; 37.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ALOX5 Gene

Human Gene Mutation Database (HGMD)
ALOX5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ALOX5
Leiden Open Variation Database (LOVD)
ALOX5

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ALOX5 Gene

Disorders for ALOX5 Gene

MalaCards: The human disease database

(41) MalaCards diseases for ALOX5 Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
asthma
  • asthma, susceptibility to
exercise-induced bronchoconstriction
  • exercise-induced asthma
atherosclerosis susceptibility
  • aths
allergic rhinitis
  • alrh
arthus reaction
  • arthus phenomenon
- elite association - COSMIC cancer census association via MalaCards
Search ALOX5 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ALOX5

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with ALOX5: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ALOX5 Gene

Publications for ALOX5 Gene

  1. Role of cyclooxygenase-2 and 5-lipoxygenase polymorphisms in Alzheimer's disease in a population from northern Italy: implication for pharmacogenomics. (PMID: 20110601) Listì F … Candore G (Journal of Alzheimer's disease : JAD 2010) 3 22 40
  2. Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. (PMID: 19233132) Strid T … Hammarström S (Biochemical and biophysical research communications 2009) 3 4 22
  3. Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export. (PMID: 18978352) Flamand N … Brock TG (The Journal of biological chemistry 2009) 3 4 22
  4. Human Dicer C-terminus functions as a 5-lipoxygenase binding domain. (PMID: 19022417) Dincbas-Renqvist V … Provost P (Biochimica et biophysica acta 2009) 3 4 22
  5. 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. (PMID: 19214143) Tantisira KG … Weiss ST (Pharmacogenetics and genomics 2009) 3 22 40

ExternalLinks

View latest publications for ALOX5 gene in Mastermind

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