Human Gene ALOX5 (ENST00000374391.7) from GENCODE V44
  Description: Homo sapiens arachidonate 5-lipoxygenase (ALOX5), transcript variant 5, mRNA. (from RefSeq NM_001320862)
RefSeq Summary (NM_000698): 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].
Gencode Transcript: ENST00000374391.7
Gencode Gene: ENSG00000012779.12
Transcript (Including UTRs)
   Position: hg38 chr10:45,374,216-45,446,117 Size: 71,902 Total Exon Count: 14 Strand: +
Coding Region
   Position: hg38 chr10:45,374,280-45,445,687 Size: 71,408 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:45,374,216-45,446,117)mRNA (may differ from genome)Protein (674 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: LOX5_HUMAN
DESCRIPTION: RecName: Full=Arachidonate 5-lipoxygenase; Short=5-LO; Short=5-lipoxygenase; EC=1.13.11.34;
FUNCTION: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
CATALYTIC ACTIVITY: Arachidonate + O(2) = leukotriene A(4) + H(2)O.
COFACTOR: Binds 1 iron ion per subunit.
COFACTOR: Binds 2 calcium ions per subunit (By similarity).
PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis.
SUBUNIT: Interacts with ALOX5AP and LTC4S.
INTERACTION: Q14019:COTL1; NbExp=4; IntAct=EBI-79934, EBI-79926;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus matrix. Nucleus membrane; Peripheral membrane protein. Note=Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser-272. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association.
PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-523 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus.
SIMILARITY: Belongs to the lipoxygenase family.
SIMILARITY: Contains 1 lipoxygenase domain.
SIMILARITY: Contains 1 PLAT domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ALOX5ID42985ch10q11.html";

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ALOX5
Diseases sorted by gene-association score: asthma* (278), arthus reaction (13), paranasal sinus disease (9), allergic rhinitis (8), glutathione synthetase deficiency (8), pleurisy (7), morphine dependence (7), tuberculous meningitis (6), hydrops, lactic acidosis, and sideroblastic anemia (6), atherosclerosis (6), pleural disease (4), acne (3), bronchial disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C063449 zileuton
  • C036837 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
  • D009637 Nordihydroguaiaretic Acid
  • C058691 5-hexyloxy-3',4'-dihydroxy-6,7-dimethoxyflavone 4'-phosphate
  • C060893 L 663536
  • C006312 FPL 55712
  • C075799 ICI D2138
  • D007975 Leukotriene B4
  • D015772 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
  • D001564 Benzo(a)pyrene
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 150.31 RPKM in Whole Blood
Total median expression: 561.63 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.9064-0.405 Picture PostScript Text
3' UTR -119.60430-0.278 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008976 - Lipase_LipOase
IPR000907 - LipOase
IPR013819 - LipOase_C
IPR020834 - LipOase_CS
IPR020833 - LipOase_Fe_BS
IPR001024 - LipOase_LH2
IPR001885 - LipOase_mml

Pfam Domains:
PF00305 - Lipoxygenase
PF01477 - PLAT/LH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2ABV - Model 3O8Y - X-ray MuPIT 3V92 - X-ray MuPIT 3V98 - X-ray MuPIT 3V99 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P09917
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004051 arachidonate 5-lipoxygenase activity
GO:0005506 iron ion binding
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO:0046872 metal ion binding
GO:0051213 dioxygenase activity

Biological Process:
GO:0002540 leukotriene production involved in inflammatory response
GO:0006691 leukotriene metabolic process
GO:0006954 inflammatory response
GO:0019221 cytokine-mediated signaling pathway
GO:0019370 leukotriene biosynthetic process
GO:0019372 lipoxygenase pathway
GO:0035655 interleukin-18-mediated signaling pathway
GO:0042759 long-chain fatty acid biosynthetic process
GO:0043312 neutrophil degranulation
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005641 nuclear envelope lumen
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0016363 nuclear matrix
GO:0031965 nuclear membrane
GO:0034774 secretory granule lumen
GO:1904813 ficolin-1-rich granule lumen


-  Descriptions from all associated GenBank mRNAs
  AB208946 - Homo sapiens mRNA for arachidonate 5-lipoxygenase variant protein.
AK225603 - Homo sapiens mRNA for arachidonate 5-lipoxygenase variant, clone: PNC01679.
BC130332 - Homo sapiens arachidonate 5-lipoxygenase, mRNA (cDNA clone MGC:163204 IMAGE:40146363), complete cds.
BC132677 - Homo sapiens arachidonate 5-lipoxygenase, mRNA (cDNA clone MGC:164308 IMAGE:40146699), complete cds.
BC143985 - Homo sapiens arachidonate 5-lipoxygenase, mRNA (cDNA clone MGC:177520 IMAGE:9052503), complete cds.
BC143986 - Homo sapiens cDNA clone IMAGE:9052504, with apparent retained intron.
AK315223 - Homo sapiens cDNA, FLJ96221.
BC034464 - Homo sapiens arachidonate 5-lipoxygenase, mRNA (cDNA clone IMAGE:5167205).
BC040450 - Homo sapiens arachidonate 5-lipoxygenase, mRNA (cDNA clone IMAGE:5178131).
J03600 - Human lipoxygenase mRNA, complete cds.
JD138954 - Sequence 119978 from Patent EP1572962.
J03571 - Human 5-lipoxygenase mRNA, complete cds.
E02559 - cDNA encoding human5'-lipoxygenase.
E02572 - cDNA sequence encoding human 5-lipoxygenase.
AB590536 - Synthetic construct DNA, clone: pFN21AE2051, Homo sapiens ALOX5 gene for arachidonate 5-lipoxygenase, without stop codon, in Flexi system.
HQ258335 - Synthetic construct Homo sapiens clone IMAGE:100072644 arachidonate 5-lipoxygenase (ALOX5) gene, encodes complete protein.
KJ890662 - Synthetic construct Homo sapiens clone ccsbBroadEn_00056 ALOX5 gene, encodes complete protein.
KR711721 - Synthetic construct Homo sapiens clone CCSBHm_00028873 ALOX5 (ALOX5) mRNA, encodes complete protein.
E02159 - Human 5-lipoxygenase gene.
JQ728550 - Homo sapiens LOX-5 splice variant (ALOX5) mRNA, complete cds, alternatively spliced.
HM592258 - Homo sapiens arachidonic 5-lipoxygenase (ALOX5) mRNA, complete cds, alternatively spliced.
HM592259 - Homo sapiens arachidonic 5-lipoxygenase delta-13 isoform (ALOX5) mRNA, complete cds, alternatively spliced.
HM592260 - Homo sapiens arachidonic 5-lipoxygenase alpha-10 isoform (ALOX5) mRNA, complete cds, alternatively spliced.
HM592261 - Homo sapiens arachidonic 5-lipoxygenase delta-p10 isoform (ALOX5) mRNA, complete cds, alternatively spliced.
JD413900 - Sequence 394924 from Patent EP1572962.
JD170362 - Sequence 151386 from Patent EP1572962.
JD270665 - Sequence 251689 from Patent EP1572962.
JD383319 - Sequence 364343 from Patent EP1572962.
JD104046 - Sequence 85070 from Patent EP1572962.
JD190157 - Sequence 171181 from Patent EP1572962.
JD349312 - Sequence 330336 from Patent EP1572962.
JD534317 - Sequence 515341 from Patent EP1572962.
JD051003 - Sequence 32027 from Patent EP1572962.
JD370950 - Sequence 351974 from Patent EP1572962.
JD333444 - Sequence 314468 from Patent EP1572962.
JD561560 - Sequence 542584 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00590 - Arachidonic acid metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
PWY-8056 - anandamide lipoxygenation
PWY66-375 - leukotriene biosynthesis
PWY66-392 - lipoxin biosynthesis
PWY66-393 - 15-epi-lipoxin biosynthesis
PWY66-394 - aspirin triggered resolvin E biosynthesis
PWY66-395 - aspirin triggered resolvin D biosynthesis
PWY66-397 - resolvin D biosynthesis

BioCarta from NCI Cancer Genome Anatomy Project
h_eicosanoidPathway - Eicosanoid Metabolism

Reactome (by CSHL, EBI, and GO)

Protein P09917 (Reactome details) participates in the following event(s):

R-HSA-429016 ALOX5 is phosphorylated by MAPKAP2
R-HSA-9018858 ALOX5 oxidises 18(S)-HEPE to 5(S)-Hp-18(S)-HEPE
R-HSA-9018859 ALOX5 oxidises 5(S)-Hp-18(S)-HEPE to 5S,6S-epoxy-18(S)-HEPE
R-HSA-9018863 ALOX5 oxidises 18(R)-HEPE to 5(S)-Hp-18(R)-HEPE
R-HSA-9018894 ALOX5 oxidises 5(S)-Hp-18(R)-HEPE to 5S,6S-epoxy-18(R)-HEPE
R-HSA-9020251 ALOX5 oxidises 17(R)-HDHA to 7(S)-Hp-17(R)-HDHA
R-HSA-9020255 ALOX5 dehydrogenates 7(S)-Hp-17(S)-HDHA to 7S(8)-epoxy-17S-HDHA
R-HSA-9020256 ALOX5 dehydrogenates 7(S)-Hp-17R-HDHA to 7S(8)-epoxy-17R-HDHA
R-HSA-9020259 ALOX5 oxidises 17(R)-HDHA to 4(S)-Hp-17(R)-HDHA
R-HSA-9020264 ALOX5 oxidises 17(S)-HDHA to 4(S)-Hp-17(S)-HDHA
R-HSA-9020277 ALOX5 dehydrogenates 4(S)-Hp-17(S)-HDHA to 4S(5)-epoxy-17(S)-HDHA
R-HSA-9020278 ALOX5 dehydrogenates 4(S)-Hp-17(R)-HDHA to 4S(5)-epoxy-17(R)-HDHA
R-HSA-9020282 ALOX5 oxidises 17(S)-HDHA to 7(S)-Hp-17(S)-HDHA
R-HSA-9024997 ALOX5 oxidises 14(S)-Hp-DHA to 7(S),14(S)-diHp-DHA
R-HSA-9025995 ALOX5 dehydrogenates 7,17-diHp-DPAn-3 to 7,8-epoxy,17-HDPAn-3
R-HSA-9025996 ALOX5 oxidises 17(S)-Hp-DPAn-3 to 7,17-diHp-DPAn-3
R-HSA-9025999 ALOX5 dehydrogenates 17(S)-Hp-DPAn-3 to 16(S),17(S)-epoxy-DPAn-3
R-HSA-9026005 ALOX5 oxidises 14(S)-Hp-DPAn-3 to MaR3n-3 DPA
R-HSA-9026405 ALOX5 oxidises 13(R)-HDPAn-3 to RvT1-4
R-HSA-9027624 ALOX5 oxidises DHA to 7-HDHA
R-HSA-9027628 ALOX5 oxidises EPA to 5-HEPE
R-HSA-9027633 ALOX5 oxidises DPAn-3 to 7-HDPAn-3
R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-6798748 Exocytosis of secretory granule lumen proteins
R-HSA-265296 Arachidonic acid is oxidised to 5S-HpETE by ALOX5
R-HSA-266051 5S-HpETE is dehydrated to LTA4 by ALOX5
R-HSA-266050 LTA4 is converted to LTC4 by LTC4S
R-HSA-2161907 15R-HETE is converted to 15epi-LXA4/B4 by ALOX5
R-HSA-2161917 15S-HpETE is oxidised to LXA4/B4 by ALOX5
R-HSA-2161768 EXA4 is converted to EXC4 by LTC4S
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-9012546 Interleukin-18 signaling
R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins
R-HSA-9023661 Biosynthesis of E-series 18(R)-resolvins
R-HSA-9020265 Biosynthesis of aspirin-triggered D-series resolvins
R-HSA-9018676 Biosynthesis of D-series resolvins
R-HSA-9018682 Biosynthesis of maresins
R-HSA-9026286 Biosynthesis of DPAn-3-derived protectins and resolvins
R-HSA-9026290 Biosynthesis of DPAn-3-derived maresins
R-HSA-9026403 Biosynthesis of DPAn-3-derived 13-series resolvins
R-HSA-9027604 Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives
R-HSA-6798695 Neutrophil degranulation
R-HSA-2142753 Arachidonic acid metabolism
R-HSA-449147 Signaling by Interleukins
R-HSA-446652 Interleukin-1 family signaling
R-HSA-9018679 Biosynthesis of EPA-derived SPMs
R-HSA-9018677 Biosynthesis of DHA-derived SPMs
R-HSA-9025094 Biosynthesis of DPAn-3 SPMs
R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs)
R-HSA-168249 Innate Immune System
R-HSA-8978868 Fatty acid metabolism
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-9018683 Biosynthesis of DPA-derived SPMs
R-HSA-2142688 Synthesis of 5-eicosatetraenoic acids
R-HSA-2142700 Synthesis of Lipoxins (LX)
R-HSA-168256 Immune System
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000374391.1, ENST00000374391.2, ENST00000374391.3, ENST00000374391.4, ENST00000374391.5, ENST00000374391.6, LOG5, LOX5_HUMAN, NM_001320862, P09917, Q5JQ14, uc001jce.1, uc001jce.2, uc001jce.3, uc001jce.4, uc001jce.5, uc001jce.6
UCSC ID: ENST00000374391.7
RefSeq Accession: NM_000698
Protein: P09917 (aka LOX5_HUMAN)
CCDS: CCDS7212.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.