Human Gene ALOX12 (uc002gdx.4) Description and Page Index
  Description: Homo sapiens arachidonate 12-lipoxygenase (ALOX12), mRNA.
RefSeq Summary (NM_000697): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: M62982.1, M35418.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2145893, SAMEA2147975 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000251535.11/ ENSP00000251535.6 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr17:6,899,384-6,914,055 Size: 14,672 Total Exon Count: 14 Strand: +
Coding Region
   Position: hg19 chr17:6,899,437-6,913,742 Size: 14,306 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:6,899,384-6,914,055)mRNA (may differ from genome)Protein (663 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: LOX12_HUMAN
DESCRIPTION: RecName: Full=Arachidonate 12-lipoxygenase, 12S-type; Short=12S-LOX; Short=12S-lipoxygenase; EC=1.13.11.31; AltName: Full=Platelet-type lipoxygenase 12;
FUNCTION: Oxygenase and 14,15-leukotriene A4 synthase activity.
CATALYTIC ACTIVITY: Arachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)- 12-hydroperoxyicosa-5,8,10,14-tetraenoate.
COFACTOR: Binds 1 iron ion per subunit.
PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis.
INTERACTION: P13647:KRT5; NbExp=7; IntAct=EBI-1633210, EBI-702187; P02545:LMNA; NbExp=4; IntAct=EBI-1633210, EBI-351935;
SUBCELLULAR LOCATION: Cytoplasm.
SIMILARITY: Belongs to the lipoxygenase family.
SIMILARITY: Contains 1 lipoxygenase domain.
SIMILARITY: Contains 1 PLAT domain.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/alox12/";
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ALOX12ID620ch17p13.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ALOX12
CDC HuGE Published Literature: ALOX12
Positive Disease Associations: bipolar disorder , bone density , colorectal cancer , hypertension , lung cancer , menopause
Related Studies:
  1. bipolar disorder
    Fridman, C. et al. 2003, Association of a new polymorphism in ALOX12 gene with bipolar disorder., European archives of psychiatry and clinical neuroscience. 2003 Feb;253(1):40-3. [PubMed 12664313]
    An increased presence of allele A among patients was found, suggesting an association of this polymorphism with the BPD in this Brazilian sample.
  2. bone density
    Ichikawa, S. et al. 2006, Human ALOX12, but Not ALOX15, Is Associated With BMD in White Men and Women, J Bone Miner Res 2006 21(4) 556-64. [PubMed 16598376]
    Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.
  3. bone density
    Mullin, B. H. et al. 2007, Polymorphisms in ALOX12, but not ALOX15, Are Significantly Associated With BMD in Postmenopausal Women, Calcif Tissue Int 2007. [PubMed 17520163]
    we found no association between polymorphism in ALOX15 and BMD phenotypes but were able to replicate previous findings that genetic variation in ALOX12 seems to play a role in determining bone structure in Caucasian women.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: ALOX12
Diseases sorted by gene-association score: inflammatory bowel disease 12 (13), colorectal cancer 12 (12), toxoplasmosis (10), prostate cancer (3), colorectal cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.29 RPKM in Vagina
Total median expression: 105.14 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 -19.8053-0.374 Picture PostScript Text
3' UTR -81.62313-0.261 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

SCOP Domains:
48484 - Lipoxigenase
49723 - Lipase/lipooxygenase domain (PLAT/LH2 domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2ABU
- Model

3D3L
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P18054
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004052 arachidonate 12-lipoxygenase activity
GO:0005506 iron ion binding
GO:0005515 protein binding
GO:0016165 linoleate 13S-lipoxygenase activity
GO:0016491 oxidoreductase activity
GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO:0016787 hydrolase activity
GO:0046872 metal ion binding
GO:0047977 hepoxilin-epoxide hydrolase activity
GO:0051120 hepoxilin A3 synthase activity
GO:0051213 dioxygenase activity

Biological Process:
GO:0006629 lipid metabolic process
GO:0006631 fatty acid metabolic process
GO:0010656 negative regulation of muscle cell apoptotic process
GO:0019369 arachidonic acid metabolic process
GO:0019372 lipoxygenase pathway
GO:0019395 fatty acid oxidation
GO:0042554 superoxide anion generation
GO:0042759 long-chain fatty acid biosynthetic process
GO:0043651 linoleic acid metabolic process
GO:0051121 hepoxilin metabolic process
GO:0051122 hepoxilin biosynthetic process
GO:0055114 oxidation-reduction process
GO:0061436 establishment of skin barrier
GO:0090331 negative regulation of platelet aggregation
GO:1901751 leukotriene A4 metabolic process
GO:2001301 lipoxin biosynthetic process
GO:2001303 lipoxin A4 biosynthetic process
GO:2001306 lipoxin B4 biosynthetic process

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0042383 sarcolemma
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  M62982 - Human arachidonate 12-lipoxygenase mRNA, complete cds.
M35418 - Human cell 12-lipoxygenase mRNA, complete cds.
M58704 - Human 12-lipoxygenase mRNA, complete cds.
BC069557 - Homo sapiens arachidonate 12-lipoxygenase, mRNA (cDNA clone MGC:97215 IMAGE:7262463), complete cds.
AB590844 - Synthetic construct DNA, clone: pFN21AE2045, Homo sapiens ALOX12 gene for arachidonate 12-lipoxygenase, without stop codon, in Flexi system.
S68587 - platelet-type 12-lipoxygenase/arachidonate 12-lipoxygenase {clone 2} [human, skin, epidermal cells, mRNA Partial, 264 nt].
S68588 - platelet-type 12-lipoxygenase/arachidonate 12-lipoxygenase {clone 1} [human, skin, epidermal cells, mRNA Partial Mutant, 264 nt].
AF143883 - Homo sapiens clone IMAGE:121454 mRNA sequence.
JD084658 - Sequence 65682 from Patent EP1572962.
JD411390 - Sequence 392414 from Patent EP1572962.
JD239313 - Sequence 220337 from Patent EP1572962.
JD228169 - Sequence 209193 from Patent EP1572962.
JD514563 - Sequence 495587 from Patent EP1572962.

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

Reactome (by CSHL, EBI, and GO)

Protein P18054 (Reactome details) participates in the following event(s):

R-HSA-2161775 LTA4 is converted to LXA4/B4 by ALOX12
R-HSA-2161794 Arachidonic acid is converted to HXA3/B3 by ALOX12
R-HSA-2161948 Arachidonic acid is converted to 12-oxoETE by ALOX12
R-HSA-9024983 ALOX12:Fe2+ dehydrogenates 14(S)-Hp-DHA to 13(S),14(S)-epoxy-DHA
R-HSA-9025957 ALOX12:Fe2+ oxidises DPAn-6 to 14(S)-HDPAn-6
R-HSA-9026006 ALOX12:Fe2+ oxidises DPAn-3 to 14(S)-Hp-DPAn-3
R-HSA-9026007 ALOX12:Fe2+ dehydrogenates 14(S)-Hp-DPAn-3 to 13,14-epoxy-DPAn-3
R-HSA-9020274 ALOX12:Fe2+ oxidises DHA to 14(S)-Hp-DHA
R-HSA-2161964 Arachidonic acid is oxidised to 12S-HpETE by ALOX12/15
R-HSA-2142700 Synthesis of Lipoxins (LX)
R-HSA-2142696 Synthesis of Hepoxilins (HX) and Trioxilins (TrX)
R-HSA-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-9018677 Biosynthesis of DHA-derived SPMs
R-HSA-9025106 Biosynthesis of DPAn-6 SPMs
R-HSA-9026290 Biosynthesis of DPAn-3-derived maresins
R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs)
R-HSA-2142753 Arachidonic acid metabolism
R-HSA-9018683 Biosynthesis of DPA-derived SPMs
R-HSA-9025094 Biosynthesis of DPAn-3 SPMs
R-HSA-8978868 Fatty acid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: LOG12, LOX12_HUMAN, NM_000697, NP_000688, O95569, P18054, Q6ISF8, Q9UQM4
UCSC ID: uc002gdx.4
RefSeq Accession: NM_000697
Protein: P18054 (aka LOX12_HUMAN)
CCDS: CCDS11084.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000697.2
exon count: 14CDS single in 3' UTR: no RNA size: 2358
ORF size: 1992CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4184.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

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