ALOX12 arachidonate 12-lipoxygenase, 12S type [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALOX12provided by HGNC
Official Full Name: arachidonate 12-lipoxygenase, 12S typeprovided by HGNC
Primary source: HGNC:HGNC:429
See related: Ensembl:ENSG00000108839 MIM:152391
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LOG12; 12-LOX; 12S-LOX
Summary: This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]
Expression: Broad expression in esophagus (RPKM 11.1), skin (RPKM 5.2) and 15 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 17p13.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (6993791..7010754)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (6899384..6914055)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

5-LOX does not react with 5,15-diHpETE, although it can produce lipoxin A4 when 15-HpETE is the substrate. In contrast, both 12-LOX and 15-LOX-1 react with 5,15-diHpETE, forming specifically lipoxin B4.
Title: 5 S,15 S-Dihydroperoxyeicosatetraenoic Acid (5,15-diHpETE) as a Lipoxin Intermediate: Reactivity and Kinetics with Human Leukocyte 5-Lipoxygenase, Platelet 12-Lipoxygenase, and Reticulocyte 15-Lipoxygenase-1.
The results suggested that genetic variation in ALOX12 might influence BMD variations in our recruited participants. As for the patients with lower serum Se levels, it was observed that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the development of osteoporosis.
Title: ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic patients.
ALOX12 missense mutations from human cancers abrogate its ability to oxygenate polyunsaturated fatty acids and to induce p53-mediated ferroptosis. Notably, ALOX12 is dispensable for ferroptosis induced by erastin or GPX4 inhibitors; conversely, ACSL4 is required for ferroptosis upon GPX4 inhibition but dispensable for p53-mediated ferroptosis
Title: ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway.
this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE-GPR31 axis that functionally determines hepatic ischemia-reperfusion injury procession
Title: An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.
This review summarizes our current knowledge on the role of 12/15-LOX in inflammation and various human diseases. [Review]
Title: Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.
ALOX15 orthologs, commonly known as 12/15-lipoxygenases, were suggested to exhibit mainly arachidonic acid 12-lipoxygenating specificity in mammals ranked in evolution lower than gibbons and 15-lipoxygenating specificity in the higher ranking primates [Review].
Title: The evolutionary hypothesis of reaction specificity of mammalian ALOX15 orthologs.
ALOX12 rs14309 GG genotype expression was found to be significantly associated with Cardiovascular events in patients with Diabetic Nephropathy.
Title: Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy.
Data suggest that ALOX12 is involved in oxidative stress and endoplasmic reticulum stress in liver and other tissues leading to non-alcoholic fatty liver disease. [REVIEW]
Title: Molecular mechanisms of nonalcoholic fatty liver disease: Potential role for 12-lipoxygenase.
12(S)-HETrE, a 12-lipoxygenase oxylipin of dihomo-gamma-linolenic acid, inhibits thrombosis via Galphas signaling in platelets.
Title: 12(S)-HETrE, a 12-Lipoxygenase Oxylipin of Dihomo-γ-Linolenic Acid, Inhibits Thrombosis via Gαs Signaling in Platelets.
Results identified a novel ALOX12 locus (indicated by two SNPs in perfect linkage disequilibrium: rs1042357 and rs10852889) that moderated the association between PTSD and reduced thickness of the right prefrontal cortex.
Title: A novel locus in the oxidative stress-related gene ALOX12 moderates the association between PTSD and thickness of the prefrontal cortex.

Submit: New GeneRIF Correction See all GeneRIFs (97)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Antifolate resistance, organism-specific biosystem (from KEGG)
Antifolate resistance, organism-specific biosystemSince the 1940s, antifolates have played a pivotal role in drug treatment of malignant, microbial, parasitic and chronic inflammatory diseases. The molecular basis of the anti-proliferative activity ...
Antifolate resistance, conserved biosystem (from KEGG)
Antifolate resistance, conserved biosystemSince the 1940s, antifolates have played a pivotal role in drug treatment of malignant, microbial, parasitic and chronic inflammatory diseases. The molecular basis of the anti-proliferative activity ...
Arachidonic acid metabolism, organism-specific biosystem (from KEGG)
Arachidonic acid metabolism, organism-specific biosystem
Arachidonic acid metabolism
Arachidonic acid metabolism, organism-specific biosystem (from REACTOME)
Arachidonic acid metabolism, organism-specific biosystemEicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth...
Arachidonic acid metabolism, conserved biosystem (from KEGG)
Arachidonic acid metabolism, conserved biosystem
Arachidonic acid metabolism
Eicosanoid Synthesis, organism-specific biosystem (from WikiPathways)
Eicosanoid Synthesis, organism-specific biosystemIn biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, (EFAs). They exert complex control over many bodily systems, mainly in inflammation or i...
Inflammatory mediator regulation of TRP channels, organism-specific biosystem (from KEGG)
Inflammatory mediator regulation of TRP channels, organism-specific biosystemThe TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive...
Inflammatory mediator regulation of TRP channels, conserved biosystem (from KEGG)
Inflammatory mediator regulation of TRP channels, conserved biosystemThe TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive...
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Serotonergic synapse, organism-specific biosystem (from KEGG)
Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
Synthesis of 12-eicosatetraenoic acid derivatives, organism-specific biosystem (from REACTOME)
Synthesis of 12-eicosatetraenoic acid derivatives, organism-specific biosystemThe 12-eicosatetraenoic acids: 12-hydroperoxy-eicosatetraenoic acid (12-HpETE), 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-oxo-eicosatetraenoic acid (12-oxoETE) are formed after the initial ste...
Synthesis of Hepoxilins (HX) and Trioxilins (TrX), organism-specific biosystem (from REACTOME)
Synthesis of Hepoxilins (HX) and Trioxilins (TrX), organism-specific biosystemHepoxilins are biologically relevant signalling molecules produced by certain arachidonate 12-lipoxygenase (ALOX12s). Hepoxilin A3 (HXA3) and B3 (HXB3) have been identified, both of which incorporate...
Synthesis of Lipoxins (LX), organism-specific biosystem (from REACTOME)
Synthesis of Lipoxins (LX), organism-specific biosystemLipoxins A4 (LXA4) and B4 (LXB4), structurally characterized from human neutrophils incubated with 15-hydroperoxy-eicosatetraenoic acid (15-HpETE), each contain three hydroxyl moieties and a conjugat...
lipoxin biosynthesis, organism-specific biosystem (from BIOCYC)
lipoxin biosynthesis, organism-specific biosystemGeneral Background Lipoxins belong to the eicosanoid family, have a distinct conjugated tetraene structure and are generated from : ARACHIDONIC_ACID during inflammation. They consist of two distinct...
lipoxin biosynthesis, conserved biosystem (from BIOCYC)
lipoxin biosynthesis, conserved biosystemGeneral Background Lipoxins belong to the eicosanoid family, have a distinct conjugated tetraene structure and are generated from |FRAME: ARACHIDONIC_ACID| during inflammation. They consist of two d...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

csnpalox12-pcr1-1 (e-PCR)
- UniSTS:242983

SHGC-12725 (e-PCR)
- UniSTS:67637

GDB:607713 (e-PCR)
- UniSTS:158269

WI-17813 (e-PCR)
- UniSTS:18653

RH122370 (e-PCR)
- UniSTS:138467

RH102167 (e-PCR)
- UniSTS:96501

Homology

Homologs of the ALOX12 gene: The ALOX12 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, and M.oryzae.
Orthologs from Annotation Pipeline: 100 organisms have orthologs with human gene ALOX12
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
arachidonate 12-lipoxygenase activity	IDA Inferred from Direct Assay more info	PubMed
hepoxilin-epoxide hydrolase activity	ISS Inferred from Sequence or Structural Similarity more info
iron ion binding	IEA Inferred from Electronic Annotation more info
linoleate 13S-lipoxygenase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
aging	IEA Inferred from Electronic Annotation more info
arachidonic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
arachidonic acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
cellular response to lipid	IEA Inferred from Electronic Annotation more info
establishment of skin barrier	ISS Inferred from Sequence or Structural Similarity more info
fatty acid oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
hepoxilin biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
hepoxilin metabolic process	TAS Traceable Author Statement more info
leukotriene A4 metabolic process	IDA Inferred from Direct Assay more info	PubMed
NOT leukotriene A4 metabolic process	IDA Inferred from Direct Assay more info	PubMed
linoleic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
NOT linoleic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
lipoxin A4 biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
lipoxin B4 biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
lipoxin biosynthetic process	TAS Traceable Author Statement more info
lipoxygenase pathway	IDA Inferred from Direct Assay more info	PubMed
lipoxygenase pathway	TAS Traceable Author Statement more info
long-chain fatty acid biosynthetic process	TAS Traceable Author Statement more info
negative regulation of muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of platelet aggregation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of blood vessel diameter	IEA Inferred from Electronic Annotation more info
positive regulation of blood vessel endothelial cell migration	IEA Inferred from Electronic Annotation more info
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of endothelial tube morphogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
positive regulation of mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
positive regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
superoxide anion generation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
membrane	IDA Inferred from Direct Assay more info	PubMed
sarcolemma	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: arachidonate 12-lipoxygenase, 12S-type

Names: 12S-lipoxygenase; lipoxin synthase 12-LO; platelet 12-LOX; platelet-type 12-lipoxygenase; platelet-type lipoxygenase 12

NP_000688.2

EC 1.13.11.31

XP_011522082.1

EC 1.13.11.31

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000697.3 → NP_000688.2 arachidonate 12-lipoxygenase, 12S-type

See identical proteins and their annotated locations for NP_000688.2

Status: REVIEWED

Source sequence(s)

AC040977, M58704

Consensus CDS

CCDS11084.1

UniProtKB/Swiss-Prot

P18054

Related

ENSP00000251535.6, ENST00000251535.11

Conserved Domains (2) summary

cd01753
Location:2 → 111

PLAT_LOX; PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and ...

pfam00305
Location:219 → 654

Lipoxygenase; Lipoxygenase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p13 Primary Assembly

Range

6993791..7010754

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011523780.2 → XP_011522082.1 arachidonate 12-lipoxygenase, 12S-type isoform X1

Conserved Domains (2) summary

cd01753
Location:121 → 230

PLAT_LOX; PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and ...

pfam00305
Location:390 → 704

Lipoxygenase; Lipoxygenase