QSOX1 explained

Quiescin sulfhydryl oxidase 1 is an enzyme that in humans is encoded by the QSOX1 gene.^{[1] [2] [3]}

This gene encodes an enzyme that is localized primarily to the Golgi apparatus and secreted fluids.^[4] QSOX1 is a multi-domain disulfide catalyst. Unlike other disulfide catalysts, QSOX1 can both generate disulfides de novo and catalyze dithiol/disulfide exchange. The de novo disulfide bond formation is catalyzed by the ERV1 domain that contains a FAD co-factor that allows depositions of electrons onto the terminal electron acceptor, typically molecular oxygen. The dithiol/disulfide exchange is catalyzed by the thioredoxin domain. The two domains are linked together by a flexible linker that allows the thioredoxin domain to first interact with the substrate protein and then regenerate by ERV1 domain.^[5]

QSOX1 gene expression is induced as fibroblasts begin to exit the proliferative cycle and enter quiescence,^{[6] [7]} suggesting that this gene plays an important role in growth regulation. In fibroblasts QSOX1 is required for normal incorporation of laminin into the extracellular matrix, and thereby for normal cell-cell adhesion and cell migration.^[8]

Two transcript variants encoding two different isoforms have been found for this gene.^[9] The two isoforms have different tissue distribution and in addition isoform 1 has a transmembrane helix in the carboxy terminal while isoform 2 is a secreted soluble protein.

Further reading

• Thorpe C, Hoober KL, Raje S, Glynn NM, Burnside J, Turi GK, Coppock DL . Sulfhydryl oxidases: emerging catalysts of protein disulfide bond formation in eukaryotes . Archives of Biochemistry and Biophysics . 405 . 1 . 1–12 . September 2002 . 12176051 . 10.1016/S0003-9861(02)00337-5 .
• Hoober KL, Glynn NM, Burnside J, Coppock DL, Thorpe C . Homology between egg white sulfhydryl oxidase and quiescin Q6 defines a new class of flavin-linked sulfhydryl oxidases . The Journal of Biological Chemistry . 274 . 45 . 31759–31762 . November 1999 . 10542195 . 10.1074/jbc.274.45.31759 . free .
• Coppock D, Kopman C, Gudas J, Cina-Poppe DA . Regulation of the quiescence-induced genes: quiescin Q6, decorin, and ribosomal protein S29 . Biochemical and Biophysical Research Communications . 269 . 2 . 604–610 . March 2000 . 10708601 . 10.1006/bbrc.2000.2324 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–2270 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .

]* Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .

• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–2080 . 2006 . 16335952 . 1850943 . 10.1021/pr0502065 .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–814 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Chakravarthi S, Jessop CE, Willer M, Stirling CJ, Bulleid NJ . Intracellular catalysis of disulfide bond formation by the human sulfhydryl oxidase, QSOX1 . The Biochemical Journal . 404 . 3 . 403–411 . June 2007 . 17331072 . 1896280 . 10.1042/BJ20061510 .
• Jaje J, Wolcott HN, Fadugba O, Cripps D, Yang AJ, Mather IH, Thorpe C . A flavin-dependent sulfhydryl oxidase in bovine milk . Biochemistry . 46 . 45 . 13031–13040 . November 2007 . 17944490 . 2518652 . 10.1021/bi7016975 .

Notes and References

1. Coppock DL, Cina-Poppe D, Gilleran S . The quiescin Q6 gene (QSCN6) is a fusion of two ancient gene families: thioredoxin and ERV1 . Genomics . 54 . 3 . 460–468 . December 1998 . 9878249 . 10.1006/geno.1998.5605 . free .
2. Coppock DL, Kopman C, Scandalis S, Gilleran S . Preferential gene expression in quiescent human lung fibroblasts . Cell Growth & Differentiation . 4 . 6 . 483–493 . June 1993 . 8396966 .
3. Web site: Entrez Gene: QSCN6 quiescin Q6.
4. Kodali VK, Thorpe C . Oxidative protein folding and the Quiescin-sulfhydryl oxidase family of flavoproteins . Antioxidants & Redox Signaling . 13 . 8 . 1217–1230 . October 2010 . 20136510 . 10.1089/ars.2010.3098 . 2959182 .
5. Alon A, Grossman I, Gat Y, Kodali VK, DiMaio F, Mehlman T, Haran G, Baker D, Thorpe C, Fass D . The dynamic disulphide relay of quiescin sulphydryl oxidase . Nature . 488 . 7411 . 414–418 . August 2012 . 22801504 . 10.1038/nature11267 . 3521037 .
6. Coppock DL, Cina-Poppe D, Gilleran S . The quiescin Q6 gene (QSCN6) is a fusion of two ancient gene families: thioredoxin and ERV1 . Genomics . 54 . 3 . 460–468 . December 1998 . 9878249 . 10.1006/geno.1998.5605 . free .
7. Coppock DL, Kopman C, Scandalis S, Gilleran S . Preferential gene expression in quiescent human lung fibroblasts . Cell Growth & Differentiation . 4 . 6 . 483–493 . June 1993 . 8396966 .
8. Ilani T, Alon A, Grossman I, Horowitz B, Kartvelishvily E, Cohen SR, Fass D . A secreted disulfide catalyst controls extracellular matrix composition and function . Science . 341 . 6141 . 74–76 . July 2013 . 23704371 . 10.1126/science.1238279 .
9. • Radom J, Colin D, Thiebault F, Dognin-Bergeret M, Mairet-Coello G, Esnard-Feve A, Fellmann D, Jouvenot M . Identification and expression of a new splicing variant of FAD-sulfhydryl oxidase in adult rat brain . Biochimica et Biophysica Acta . 1759 . 5 . 225–233 . May 2006 . 16806532 . 10.1016/j.bbaexp.2006.04.008 .