Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
drug target
-
QSOX is a potential target for blocking parasite transmission
drug target
-
QSOX is a potential target for blocking parasite transmission
-
evolution
-
augmenter of liver regeneration is a member of the ERV family of small flavin-dependent sulfhydryl oxidases that contain a redox-active CxxC disulfide bond in redox communication with the isoalloxazine ring of bound FAD
evolution
-
enzyme QSOX is an evolutionarily conserved protein present in organisms ranging from the smallest free-living eukaryotes to humans
evolution
-
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
evolution
-
mechanistic parallels between the eukaryotic QSOX enzymes and the DsbA/B system catalyzing disulfide bond generation in the bacterial periplasm are detected suggesting that the strategy of linked disulfide exchanges may be exploited in other catalysts of oxidative protein folding
evolution
the enzyme belongs to a family of flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidases
evolution
-
based on the analysis of 33 fungal genomes, sulfhydryl oxidase (SOX) encoding genes are close to nonribosomal peptide synthetases (NRPS) but not with polyketide synthases (PKS). In the phylogenetic tree, constructed from 25 SOX and thioredoxin reductase sequences from IPR000103 InterPro family, the enzyme (AtSOX) is evolutionary closely related to other Aspergillus SOXs. Oxidoreductases involved in the maturation of nonribosomal peptides of fungal and bacterial origin (GliT, HlmI and DepH) are evolutionary closely related to AtSOX whereas fungal thioreductases are more distant
evolution
-
evolutionary and phylogenetic analysis analysis of QSOX, detailed overview. QSOX CXXC motifs display on the neighbor-joining phylogenetic tree. The psiErv/Erv module, strongly characteristic of QSOX, contrasts with a Trx module only weakly differentiated from PDI family domains. QSOX redox-active motifs differ between Metazoa and Viridiplantae and show enhanced diversity among paralogues. Conservation at the Trx-Erv domain interface suggests a conserved electron transfer mechanism. Intron positions do not reveal a common imprint between Viridiplantae and Metazoa
-
evolution
-
based on the analysis of 33 fungal genomes, sulfhydryl oxidase (SOX) encoding genes are close to nonribosomal peptide synthetases (NRPS) but not with polyketide synthases (PKS). In the phylogenetic tree, constructed from 25 SOX and thioredoxin reductase sequences from IPR000103 InterPro family, the enzyme (AtSOX) is evolutionary closely related to other Aspergillus SOXs. Oxidoreductases involved in the maturation of nonribosomal peptides of fungal and bacterial origin (GliT, HlmI and DepH) are evolutionary closely related to AtSOX whereas fungal thioreductases are more distant
-
malfunction
silencing Sfp53 expression does not rescue the ability of an ac92-knockout virus to produce infectious virus. Similarly, ac92 expression does not affect SfP53-stimulated caspase activity or the localization of SfP53. Although Ac92 binds to SfP53 during AcMNPV replication and oxidizes SfP53 in vitro, no effects of this interaction on AcMNPV replication in cultured cells can be detected. Overexpression or silencing of Ac92 during virus infection does not affect SfP53 accumulation
malfunction
-
substitution of the intervening E143 and E144 dipeptide by the charge-reversed KK dipeptide shows minimal effect on the redox potential
malfunction
mutations at a cis-proline in QSOX1 that is conserved across the thioredoxin superfamily result in QSOX1 variants that showed a striking detrimental effect when added exogenously to fibroblasts. They severely disrupt the extracellular matrix and cell adhesion, even in the presence of naturally secreted, wild-type enzyme (QSOX1)
malfunction
-
Pbqsox deletion (DELTApbqsox) does not affect asexual intraerythrocytic development, but reduces exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also leads to a significant increase in the reduced thiol groups of ookinete surface proteins
malfunction
-
Pbqsox deletion (DELTApbqsox) does not affect asexual intraerythrocytic development, but reduces exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also leads to a significant increase in the reduced thiol groups of ookinete surface proteins
-
physiological function
-
Erv1p is a FAD-dependent sulfhydryl oxidase and is an essential component of the redox regulated Mia40/Erv1 import and assembly pathway used by many of the cysteine-containing intermembrane space proteins
physiological function
-
enzyme gene eroA gene is essential for viability. It is able to complement the ERO1 function in the Saccharomyces cerevisiae ero1-1 mutant
physiological function
-
isoform ErvA gene ervA does not have an obvious role in the secretion of native proteins, including glucoamylase. It is able to complement the ERO1 function in the Saccharomyces cerevisiae ero1-1 mutant
physiological function
protein Alr is able to substitute for the function of Saccharomyces cerevisiae Erv1. Alr is required for mitochondrial biogenesis of human Mia40, which is responsible for the import and oxidative folding of proteins destined for the intermembrane space of mitochondria. The defective accumulation of human Mia40 in mitochondria in a recently identified disease that is caused by amino acid exchange in Alr
physiological function
-
enzymes GmQSOX1a,GmQSOX1b, and GmQSOX2a play important roles in protein folding in the endoplasmic reticulum
physiological function
-
quiescin-sulfhydryl oxidase (QSOX) plays a role in protein folding by introducing disulfides into unfolded reduced proteins. Quiescin-sulfhydryl oxidase inhibits formation of prions, infectious glycoproteins that cause a group of fatal transmissible diseases in animals and humans, in vitro. QSOX inhibits human prion propagation in protein misfolding cyclic amplification reactions and murine prion propagation in scrapie-infected neuroblastoma cells. Enzyme QSOX preferentially binds the scrapie isoform prion PrPSc from prion-infected human brains, but not PrPC from uninfected brains
physiological function
the Autographa californica M nucleopolyhedrovirus (AcMNPV) sulfhydryl oxidase Ac92 is essential for production of infectious virions. Ac92 also interacts with human protein p53 and enhances human p53-induced apoptosis in insect cell. Enzyme Ac92 interacts with protein SfP53 from Spodoptera frugiperda in infected Sf9 cells and oxidizes SfP53 in vitro. Ac92 does not affect the cellular localization of SfP53 and partially co-localizes with SfP53 in Sf9 cells. Ac92 does not interact with or oxidize a mutant of SfP53 predicted to lack DNA binding. Ac92 possibly prevents DNA binding of SfP53. Ac92 expression does not stimulate significant caspase activity on its own, nor does it stimulate HA-SfP53-mediated caspase activation above levels induced by SfP53 alone or with an empty vector in transfected Sf9 cells
physiological function
the extracellular location of QSOX proteins suggests that they may be involved in the remodelling of the extracellular matrix, particularly because QSOX can catalyse the formation of disulfide bridges, which are needed for the appropriate folding and stability of various matrix proteins. The expression of QSOX1 in neuroblastoma tumors may influence its clinical course because this protein is involved in processes such as the maturation of the extracellular matrix and the induction of apoptosis in these tumors
physiological function
-
the inability of the relatively bulky glutathione to attain the in-line geometry required for efficient disulfide exchange in sfALR may be physiologically important in preventing the oxidase from catalyzing the potentially harmful oxidation of intracellular glutathione. sfALR protects against hydrogen peroxide and radiation-induced apoptosis
physiological function
-
the reduced and denatured RNase A is effectively refolded by recombinant GmQSOX1 in the presence of the soybean protein disulfide isomerase family protein GmPDIL-2 in the absence of glutathione redox buffer. Enzymes GmQSOX1a,GmQSOX1b, and GmQSOX2a play important roles in protein folding in the endoplasmic reticulum
physiological function
among other potential functions, QSOX1 supports extracellular matrix assembly in fibroblast cultures
physiological function
-
epidermal sulfhydryl oxidase mainly cross-links keratins or keratins with other proteins within the corneous core of keratinocytes of the stratum granulare and of the transitional layer. The presence of disulphide bonds in corneocytes and of isopeptide bonds in the cell cornified envelope determines the high chemical, mechanical and antimicrobial resistance of the corneous layer
physiological function
epidermal sulfhydryl oxidase mainly cross-links keratins or keratins with other proteins within the corneous core of keratinocytes of the stratum granulare and of the transitional layer. The presence of disulphide bonds in corneocytes and of isopeptide bonds in the cell cornified envelope determines the high chemical, mechanical and antimicrobial resistance of the corneous layer
physiological function
epidermal sulfhydryl oxidase mainly cross-links keratins or keratins with other proteins within the corneous core of keratinocytes of the stratum granulare and of the transitional layer. The presence of disulphide bonds in corneocytes and of isopeptide bonds in the cell cornified envelope determines the high chemical, mechanical and antimicrobial resistance of the corneous layer
physiological function
-
epidermal sulfhydryl oxidase mainly cross-links keratins or keratins with other proteins within the corneous core of keratinocytes of the stratum granulare and of the transitional layer. The presence of disulphide bonds in corneocytes and of isopeptide bonds in the cell cornified envelope determines the high chemical, mechanical and antimicrobial resistance of the corneous layer
physiological function
-
SOXs could be involved in the secondary metabolism and act as an accessory enzyme in the production of nonribosomal peptides
physiological function
sulfhydryl oxidase P33 is necessary for budded virus (BV) production and multinucleocapsid occlusion-derived virus (ODV) formation
physiological function
-
the enzyme catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. It is required for parasite sexual development especially for ookinete maturation
physiological function
-
the extracellular enzyme (QSOX1b) transduces migratory and mitogenic responses in primary vascular smooth muscle cells by distinct pathways. The migratory pathway is triggered by active QSOX1b and depends on hydrogen peroxide from Nox1-derived superoxide. The enzyme has a role in neointima formation in balloon-injured rat carotid
physiological function
-
enzyme gene eroA gene is essential for viability. It is able to complement the ERO1 function in the Saccharomyces cerevisiae ero1-1 mutant
-
physiological function
-
isoform ErvA gene ervA does not have an obvious role in the secretion of native proteins, including glucoamylase. It is able to complement the ERO1 function in the Saccharomyces cerevisiae ero1-1 mutant
-
physiological function
-
SOXs could be involved in the secondary metabolism and act as an accessory enzyme in the production of nonribosomal peptides
-
physiological function
-
the enzyme catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. It is required for parasite sexual development especially for ookinete maturation
-
additional information
-
E143 and E144 are active site residues in the CxxC motif
additional information
-
in the redox center, CXXC motif of the thioredoxin domain is comparatively oxidizing, consistent with an ability to transfer disulfide bonds to a broad range of thiol substrates. In contrast, the proximal CXXC disulfide in the ERV (essential for respiration and vegetative growth) domain of TbQSOX is strongly reducing, representing a major apparent thermodynamic barrier to overall catalysis. Reduction of the oxidizing FAD cofactor is followed by the strongly favorable reduction of molecular oxygen, role of a mixed disulfide intermediate between thioredoxin and ERV domains, overview. Mixed disulfide bond formation is accompanied by the generation of a charge transfer complex with the flavin cofactor providing thermodynamic coupling among the three redox centers of QSOX and avoids the strongly uphill mismatch between the formal potentials of the thioredoxin and ERV disulfides. Domain organization of TbQSOX together with key catalytic steps deduced from studies of both metazoan and protist QSOXs, overview