ALOX5

Protein identityUniProt · HPA

UniProt accession

P09917

Gene

ALOX5

Ensembl

ENSG00000012779

Chromosome

10

Canonical length

674 aa

Protein class

Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

674 residues, UniProt reviewed canonical sequence.

>P09917|ALOX5
     1  MPSYTVTVAT GSQWFAGTDD YIYLSLVGSA GCSEKHLLDK PFYNDFERGA VDSYDVTVDE
    61  ELGEIQLVRI EKRKYWLNDD WYLKYITLKT PHGDYIEFPC YRWITGDVEV VLRDGRAKLA
   121  RDDQIHILKQ HRRKELETRQ KQYRWMEWNP GFPLSIDAKC HKDLPRDIQF DSEKGVDFVL
   181  NYSKAMENLF INRFMHMFQS SWNDFADFEK IFVKISNTIS ERVMNHWQED LMFGYQFLNG
   241  CNPVLIRRCT ELPEKLPVTT EMVECSLERQ LSLEQEVQQG NIFIVDFELL DGIDANKTDP
   301  CTLQFLAAPI CLLYKNLANK IVPIAIQLNQ IPGDENPIFL PSDAKYDWLL AKIWVRSSDF
   361  HVHQTITHLL RTHLVSEVFG IAMYRQLPAV HPIFKLLVAH VRFTIAINTK AREQLICECG
   421  LFDKANATGG GGHVQMVQRA MKDLTYASLC FPEAIKARGM ESKEDIPYYF YRDDGLLVWE
   481  AIRTFTAEVV DIYYEGDQVV EEDPELQDFV NDVYVYGMRG RKSSGFPKSV KSREQLSEYL
   541  TVVIFTASAQ HAAVNFGQYD WCSWIPNAPP TMRAPPPTAK GVVTIEQIVD TLPDRGRSCW
   601  HLGAVWALSQ FQENELFLGM YPEEHFIEKP VKEAMARFRK NLEAIVSVIA ERNKKKQLPY
   661  YYLSPDRIPN SVAI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALOX5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.2

Highest tissue expression

90 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.64

gnomAD pLI

0

gnomAD missense Z

1.09

DepMap mean gene effect

-0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• arachidonate metabolic process
• dendritic cell migration
• glucose homeostasis
• humoral immune response
• leukocyte chemotaxis involved in inflammatory response
• leukocyte migration involved in inflammatory response
• leukotriene biosynthetic process
• leukotriene metabolic process
• leukotriene production involved in inflammatory response
• lipid oxidation
• lipoxygenase pathway
• long-chain fatty acid biosynthetic process
• negative regulation of angiogenesis
• negative regulation of endothelial cell proliferation
• negative regulation of inflammatory response
• negative regulation of response to endoplasmic reticulum stress
• negative regulation of sprouting angiogenesis
• negative regulation of vascular wound healing
• negative regulation of wound healing
• positive regulation of bone mineralization
• positive regulation of leukocyte adhesion to arterial endothelial cell
• regulation of cellular response to oxidative stress
• regulation of cytokine production involved in inflammatory response
• regulation of fat cell differentiation
• regulation of inflammatory response
• regulation of insulin secretion
• regulation of reactive oxygen species biosynthetic process
• leukotriene A4 biosynthetic process
• lipoxin biosynthetic process
• regulation of inflammatory response to wounding

Molecular functions

• arachidonate 12(S)-lipoxygenase activity
• arachidonate 8(S)-lipoxygenase activity
• hydrolase activity
• iron ion binding
• oxidoreductase activity
• oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
• arachidonate 5-lipoxygenase activity

Cellular components

• cytosol
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• nuclear envelope
• nuclear envelope lumen
• nuclear matrix
• nuclear membrane
• nucleoplasm
• perinuclear region of cytoplasm
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• Lipoxygenase
• PLAT/LH2 domain
• Lipoxygenase, mammalian
• Lipoxygenase, C-terminal
• Lipoxygenase, iron binding site
• Lipoxygenase, conserved site
• Lipoxigenase, C-terminal domain superfamily
• PLAT/LH2 domain superfamily
• Lipoxygenase, vertebrates, PLAT domain
• Lipoxygenase
• PLAT/LH2 domain

KeywordsUniProt

• Calcium
• Cytoplasm
• Dioxygenase
• Hydrolase
• Iron
• Leukotriene biosynthesis
• Lipid metabolism
• Membrane
• Metal-binding
• Nucleus
• Oxidoreductase
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of ALOX5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALOX5AP
• COTL1
• LTC4S
• PIK3R1