ALOX12B

ALOX12B
Identifiers
Gene ontology
Molecular function	iron ion binding; arachidonate 12(S)-lipoxygenase activity; dioxygenase activity; metal ion binding; protein binding; catalytic activity; oxidoreductase activity; oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; linoleate 9S-lipoxygenase activity;
Cellular component	cytoplasm; cytosol;
Biological process	linoleic acid metabolic process; establishment of skin barrier; lipid metabolism; ceramide biosynthetic process; fatty acid metabolic process; lipoxygenase pathway; hepoxilin biosynthetic process; positive regulation of gene expression; protein lipidation; positive regulation of mucus secretion; sphingolipid metabolic process; positive regulation of MAPK cascade; arachidonic acid metabolic process;
	Sources:Amigo / QuickGO

Ensembl


ENSG00000179477


ENSMUSG00000032807

UniProt


O75342


O70582

RefSeq (mRNA)


NM_001139


NM_009659

RefSeq (protein)


NP_001130


NP_033789

Location (UCSC)

Chr 17: 8.07 – 8.09 Mb

Chr 11: 69.05 – 69.06 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12R-LOX, and arachidonate lipoxygenase 3, is a lipoxygenase-type enzyme composed of 701 amino acids and encoded by the ALOX12B gene.^[5]^[6]^[7] The gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOXE3 and ALOX15B.^[8] Among the human lipoxygenases, ALOX12B is most closely (54% identity) related in amino acid sequence to ALOXE3^[9]

Activity

ALOX12B oxygenates

hydroxyl analog (OH), 12(R)-hydroxy-5'Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE), by ubiquitous peroxidase

-type enzymes. These sequential metabolic reactions are:

arachidonic acid + O₂ $\rightleftharpoons$ 12R-HpETE → 12R-HETE

ALOX12B is also capable of metabolizing free linoleic acid to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE) which is also rapidly converted to its hydroxyl derivative, 9-Hydroxyoctadecadienoic acid (9R-HODE).^[10]

Linoleic acid + O₂ $\rightleftharpoons$ 9R-HpODE → 9R-HODE

The S

stereoisomer of 9R-HODE, 9S-HODE, has a range of biological activities related to oxidative stress and pain perception (see 9-Hydroxyoctadecadienoic acid. It is known or likely that 9R-HODE possesses at least some of these activities. For example, 9R-HODE, similar to 9S-HODE, mediates the perception of acute and chronic pain induced by heat, UV light, and inflammation in the skin of rodents (see 9-Hydroxyoctadecadienoic acid#9-HODEs as mediators of pain perception). However, production of these LA metabolites does not appear to be the primary function of ALOX12B; ALOX12B's primary function appears to be to metabolize linoleic acid that is not free but rather esterified to certain ^{[citation needed}

]

Proposed principal activity of ALOX12B

ALOX12B targets

Lung microbiome#Role of the epithelial barrier).^[11] ALOX12B metabolizes the LA in EOS to its 9-hydroperoxy derivative; ALOXE3 then converts this derivative to three products: a) 9R,10R-trans-epoxide,13R-hydroxy-10E-octadecenoic acid, b) 9-keto-10E,12Z-octadecadienoic acid, and c) 9R,10R-trans-epoxy-13-keto-11E-octadecenoic acid.^[11] These ALOX12B-oxidized products signal for the hydrolysis (i.e. removal) of the oxidized products from EOS; this allows the multi-step metabolic pathway to proceed in delivering the VLCFAs to the cornified lipid envelop in the skin's Stratum corneum.^[11]^[12]

Tissue distribution

ALOX12B protein has been detected in humans that in the same tissues the express ALOXE3 and ALOX15B viz., upper layers of the human skin and tongue and in tonsils.[8] mRNA for it has been detected in additional tissues such as the lung, testis, adrenal gland, ovary, prostate, and skin with lower abundance levels detected in salivary and thyroid glands, pancreas, brain, and plasma blood leukocytes.^[8]

Clinical significance

Congenital ichthyosiform erythrodema

Deletions of Alox12b or AloxE2 genes in mice cause a congenital scaly skin disease which is characterized by a greatly reduced skin water barrier function and is similar in other ways to the

mutations).^[11]

Proliferative skin diseases

In

mRNA and 12R-HETE are greatly increased.^[8] It is not clear if these increases contribute to the disease by, for example, 12R-HETE induction of inflammation, or are primarily a consequence of skin proliferation.^[11]

Embryogenesis

The expression of Alox12b and Aloxe3

orthologs of these genes, i.e. ALOX12B and ALOXE3, may have a similar role in humans.^[11]

Essential fatty acid deficiency

Severe dietary deficiency of polyunsaturated

essential fatty acid deficiency syndrome that is characterized by scaly skin and excessive water loss; in humans and animal models the syndrome is fully reversed by dietary omega 6 fatty acids, particularly linoleic acid.^[13] It is proposed that this deficiency disease resembles and has a similar basis to Congenital ichthyosiform erythrodema; that is, it is at least in part due to a deficiency of linoleic acid and thereby in the EOS-based delivery of VLCFA to the stratum corneum.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000179477 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032807 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: ALOX12B arachidonate 12-lipoxygenase, 12R type".
^
PMID 9618483
.

^
PMID 9837935
.

^
PMID 12432924
.

PMID 19244215
.

PMID 24021977
.

^
PMID 23954555
.

PMID 25316652
.

PMID 25339684
.

Further reading

Yu Z, Schneider C, Boeglin WE, Brash AR (June 2007). "Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARalpha". Lipids. 42 (6): 491–7.
S2CID 4012229
.

Lesueur F, Bouadjar B, Lefèvre C, Jobard F, Audebert S, Lakhdar H, Martin L, Tadini G, Karaduman A, Emre S, Saker S, Lathrop M, Fischer J (April 2007). "Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13". The Journal of Investigative Dermatology. 127 (4): 829–34.
PMID 17139268
.

Yu Z, Schneider C, Boeglin WE, Brash AR (January 2005). "Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1686 (3): 238–47.
PMID 15629692
.

McDonnell M, Li H, Funk CD (2002). "Characterization of Epidermal 12(S) and 12(R) Lipoxygenases". Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology. Vol. 507. pp. 147–53.
PMID 12664578
.

Schneider C, Keeney DS, Boeglin WE, Brash AR (February 2001). "Detection and cellular localization of 12R-lipoxygenase in human tonsils". Archives of Biochemistry and Biophysics. 386 (2): 268–74.
PMID 11368351
.

Krieg P, Marks F, Fürstenberger G (May 2001). "A gene cluster encoding human epidermis-type lipoxygenases at chromosome 17p13.1: cloning, physical mapping, and expression". Genomics. 73 (3): 323–30.
PMID 11350124
.

Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening". Biochemistry. 39 (12): 3185–91.
PMID 10727209
.

Boeglin WE, Kim RB, Brash AR (June 1998). "A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expression". Proceedings of the National Academy of Sciences of the United States of America. 95 (12): 6744–9.
PMID 9618483
.

External links

Human ALOX12B genome location and ALOX12B gene details page in the UCSC Genome Browser.

Retrieved from "https://en.wikipedia.org/w/index.php?title=ALOX12B&oldid=1189311572"

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000179477 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032807 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: ALOX12B arachidonate 12-lipoxygenase, 12R type".

[pmid9618483-6] 
PMID 9618483
.

[pmid9837935-7] 
PMID 9837935
.

[Schneider_2002-8] 
PMID 12432924
.

[9] PMID 19244215
.

[pmid24021977-10] PMID 24021977
.

[Krieg_2014-11] 
PMID 23954555
.

[pmid25316652-12] PMID 25316652
.

[pmid25339684-13] PMID 25339684
.

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[5]

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[8]

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