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
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Genomic context

Location:: 17p13.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (6993791..7010754)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (6899368..6914073)

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?

Biosynthesis of the Maresin Intermediate, 13S,14S-Epoxy-DHA, by Human 15-Lipoxygenase and 12-Lipoxygenase and Its Regulation through Negative Allosteric Modulators.
Title: Biosynthesis of the Maresin Intermediate, 13S,14S-Epoxy-DHA, by Human 15-Lipoxygenase and 12-Lipoxygenase and Its Regulation through Negative Allosteric Modulators.
Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer.
Title: Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer.
12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2gamma knockout.
Title: 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA<sub>2</sub>γ knockout.
Inhibition of arachidonate lipoxygenase12 targets lung cancer through inhibiting EMT and suppressing RhoA and NF-kappaB activity.
Title: Inhibition of arachidonate lipoxygenase12 targets lung cancer through inhibiting EMT and suppressing RhoA and NF-κB activity.
12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.
Title: 12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.
Alox12 overexpression was sufficient to stimulate growth in normal breast cells but not breast cancer cells. Alox12 depletion inhibited breast cancer growth and survival, and significantly enhanced the chemotherapeutic agents' efficacy.
Title: ALOX12 inhibition sensitizes breast cancer to chemotherapy via AMPK activation and inhibition of lipid synthesis.
His596 is involved in anchoring the carboxy terminal of arachidonic acid during catalysis, while Leu407 is involved in positioning the substrate correctly.
Title: Probing the Electrostatic and Steric Requirements for Substrate Binding in Human Platelet-Type 12-Lipoxygenase.
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.

Submit: New GeneRIF Correction See all GeneRIFs (104)

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

Associated conditions

Description	Tests
An atlas of genetic influences on human blood metabolites. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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: 116 organisms have orthologs with human gene ALOX12
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
arachidonate 12(S)-lipoxygenase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
arachidonate 12(S)-lipoxygenase activity	IDA Inferred from Direct Assay more info	PubMed
arachidonate 15-lipoxygenase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
arachidonate 15-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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
linoleate 13S-lipoxygenase activity	IDA Inferred from Direct Assay more info	PubMed
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	IBA Inferred from Biological aspect of Ancestor 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
fatty acid oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
hepoxilin biosynthetic process	IBA Inferred from Biological aspect of Ancestor 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	IBA Inferred from Biological aspect of Ancestor 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
lipid metabolic process	IDA Inferred from Direct Assay more info	PubMed
lipid oxidation	IBA Inferred from Biological aspect of Ancestor 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 apoptotic process	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
unsaturated fatty acid metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IBA Inferred from Biological aspect of Ancestor 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
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
sarcolemma	IBA Inferred from Biological aspect of Ancestor more info	PubMed
sarcolemma	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: polyunsaturated fatty acid lipoxygenase ALOX12

Names: 12S-lipoxygenase; Arachidonate 12-lipoxygenase, 12S-type; arachidonate (12S)-lipoxygenase; arachidonate (15S)-lipoxygenase; arachidonate 15-lipoxygenase,15S-type; linoleate 13S-lipoxygenase; lipoxin synthase 12-LO; platelet 12-LOX; platelet-type 12-lipoxygenase; platelet-type lipoxygenase 12

NP_000688.2

EC 1.13.11.31

EC 1.13.11.33

XP_011522082.1

EC 1.13.11.31

EC 1.13.11.33

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 polyunsaturated fatty acid lipoxygenase ALOX12

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:161 → 654

Lipoxygenase

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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 polyunsaturated fatty acid lipoxygenase ALOX12 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