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FLASH GENE

Symbol

GPX1

contributors: mct - updated : 09-10-2017

HGNC name	glutathione peroxidase 1
HGNC id	4553

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a polyalanine sequence polymorphism in the N-terminal region
	includes three alleles with five, six or seven alanine (ALA) repeats in this sequence

mono polymer

homomer , tetramer

HOMOLOGY

interspecies	ortholog to rattus Gpx1
	ortholog to murine Gpx1

Homologene

FAMILY

glutathione peroxidase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic

basic FUNCTION	free radical detoxification
	catabolic pathway of activated oxygen species
	involved in the protection of the hemoglobin in erythrocytes from oxidative breakdown
	implicated as a mechanism of resistance against oxygen free radicals
	plays an important role in cellular defense by converting hydrogen peroxide and organic hydroperoxides to nonreactive products
	likely a major role for GPX1 in cardiac dysfunction in ANGPT2-dependent hypertension
	modulates potentially the endothelial cell response to LPS, in part, by altering CD14-mediated effects
	selenium-containing protein, associated with cancer risk and development
	regulates leukocyte-endothelial cell interactions in the cerebral microvasculature, but that this is affected by the nature of the inflammatory insult
	GPX5 protein, and the epithelial proteins GPX1, GPX3, and cellular GPX4, all functioning in the mammalian epididymis at different stages of the sperm epididymal journey, and in different epididymis compartments
	anti-oxidant enzyme that may protect lungs from oxidative damage
	primes potentially pro-inflammatory cytokine production after LPS challenge
	GPX2 and GPX1 have overlapping functions in controlling inflammatory lipid mediator synthesis and, most probably, exert their anti-inflammatory effects by preventing excessive PGE2 production
	GPX1 and GPX4 dampen phosphorylation cascades predominantly via prevention of inactivation of phosphatases by H2O2 or lipid hydroperoxides

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

detoxification

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	other,
	selenium (Se)

protein	SELENBP1 and GPX1 form a physical association (interaction between two distinct selenium-containing proteins that may enhance the understanding of the mechanisms by which selenium and selenoproteins affect carcinogenesis)
	GPX1 is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene

cell & other

REGULATION

inhibited by

inhibited in lung cancer with 3p loss (affect prognosis of cancer)

ASSOCIATED DISORDERS

corresponding disease(s)

GPX1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     in a significant percentage of colorectal cancer constitutional       loss of function augments proinflammatory cytokine-induced redox signaling and endothelial cell activation constitutional     --low   significant reductions in expression of GPX1, GPX3, GPX4 in placentae from women with preeclampsia

Susceptibility

to breast cancer to several types of malignancies to type 2 diabetes to Keshan disease (endemic dilated cardiomyopathy) to thoracic aortic aneurysm in hypertensive patients

Variant & Polymorphism other	allele with five ALA repeats is significantly associated with breast cancer risk
	the C-->T (Pro198Leu) polymorphism is protective against thoracic aortic aneurysm in hypertensive patients
	a single nucleotide polymorphism (Pro198Leu) associated with selenium deficiency as well as impaired GPX1 activity, which may, in turn, increase the incidence of KD (Keshan disease)
	variant associated with cancer risk for several types of malignancies
	GPX1 variants might contribute to the development of diabetes type 2

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   may represent a potential therapeutic target for enhancement of regenerative capacity of endothelial progenitor cells (EPCs) in old subjects miscelleaneous vascular   overexpressing GPX1 in endothelial cells is able to change the basal mRNA and protein BAX levels without affecting those of TP53 and BCL2 (useful to antiatherogenic therapies which use antioxidants with the aim of protecting the vascular wall against ox

ANIMAL & CELL MODELS

Gpx1(-/-) mice displayed significant reductions in rolling and adhesion associated with severe blood flow restriction