Literature summary for 1.13.11.31 extracted from

Yeung, J.; Tourdot, B.E.; Fernandez-Perez, P.; Vesci, J.; Ren, J.; Smyrniotis, C.J.; Luci, D.K.; Jadhav, A.; Simeonov, A.; Maloney, D.J.; Holman, T.R.; McKenzie, S.E.; Holinstat, M.
Platelet 12-LOX is essential for FcgammaRIIa-mediated platelet activation (2014), Blood, 124, 2271-2279 .

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Application

Application	Comment	Organism
medicine	blood platelet enzyme 12-LOX modulates FcgammaRIIa signaling and presents a viable therapeutic target in the prevention of immune-mediated thrombosis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
ML355	a selective 12-LOX inhibitor, blocks both FcgammaRIIa-induced platelet aggregation and (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate production	Homo sapiens
ML355	a selective 12-LOX inhibitor, blocks both FcgammaRIIa-induced platelet aggregation and (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate production	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
arachidonate + O2	Mus musculus	-	(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate	-	?
arachidonate + O2	Homo sapiens	-	(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O75342	-	-
Mus musculus	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
blood platelet	high expression level of 12-LOX	Mus musculus	-
blood platelet	high expression level of 12-LOX	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
arachidonate + O2	-	Mus musculus	(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate	-	?
arachidonate + O2	-	Homo sapiens	(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate	-	?

Synonyms

Synonyms	Comment	Organism
12(S)-lipoxygenase	-	Mus musculus
12(S)-lipoxygenase	-	Homo sapiens
12-LOX	-	Mus musculus
12-LOX	-	Homo sapiens
oxylipin-producing enzyme	-	Mus musculus
oxylipin-producing enzyme	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	pharmacologic inhibition of 12-LOX in human platelets results in significant attenuation of FcgammaRIIa-mediated aggregation. Activation of the FcgammaRIIa receptor leads to immune-mediated thrombosis, which is often life threatening in patients undergoing heparin-induced thrombocytopenia or sepsis. Inhibiting FcgammaRIIa-mediated activation, e.g. by inhibiting the enzyme 12-LOX, in platelets limits thrombosis and is the principal target for prevention of immune-mediated platelet activation	Homo sapiens
malfunction	platelets from transgenic mice expressing human FcgammaRIIa but deficient in platelet 12-LOX, fail to form normal platelet aggregates and exhibit deficiencies in Rap1 and aIIbbeta3 activation	Mus musculus
additional information	platelets from transgenic mice expressing human FcgammaRIIa but deficient in platelet 12-LOX, fail to form normal platelet aggregates and exhibit deficiencies in Rap1 and aIIbbeta3 activation	Homo sapiens
physiological function	murine platelets require 12-LOX for normal FcgammaRIIa-induced platelet aggregation	Mus musculus
physiological function	platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of FcgammaRIIa-mediated thrombosis. Platelet enzyme 12-LOX modulates FcgammaRIIa signaling and is essential for FcgammaRIIa-mediated platelet activation. 12-LOX is essential for FcgammaRIIa-induced phospholipase Cgamma2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin aIIbbeta3. 12-LOX regulates dense and a granule secretion in FcgammaRIIa-activated platelets	Homo sapiens

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Release 2023.1 (January 2023)