ID QSOX1_HUMAN Reviewed; 747 AA. AC O00391; Q59G29; Q5T2X0; Q8TDL6; Q8WVP4; DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 3. DT 27-NOV-2024, entry version 199. DE RecName: Full=Sulfhydryl oxidase 1; DE Short=hQSOX; DE EC=1.8.3.2 {ECO:0000269|PubMed:18393449, ECO:0000269|PubMed:22801504, ECO:0000269|PubMed:23704371, ECO:0000269|PubMed:23867277, ECO:0000269|PubMed:26819240, ECO:0000269|PubMed:29757379, ECO:0000269|PubMed:30367560}; DE AltName: Full=Quiescin Q6 {ECO:0000303|PubMed:10708601, ECO:0000303|PubMed:9878249}; DE Flags: Precursor; GN Name=QSOX1; Synonyms=QSCN6 {ECO:0000303|PubMed:9878249}; GN ORFNames=UNQ2520/PRO6013; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION. RC TISSUE=Lung; RX PubMed=9878249; DOI=10.1006/geno.1998.5605; RA Coppock D.L., Cina-Poppe D., Gilleran S.; RT "The quiescin Q6 gene (QSCN6) is a fusion of two ancient gene families: RT thioredoxin and ERV1."; RL Genomics 54:460-468(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ALA-200 AND ARG-444. RC TISSUE=Placenta; RX PubMed=16806532; DOI=10.1016/j.bbaexp.2006.04.008; RA Radom J., Colin D., Thiebault F., Dognin-Bergeret M.J., Mairet-Coello G., RA Esnard-Feve A., Fellmann D., Jouvenot M.; RT "Identification and expression of a new splicing variant of FAD-sulfhydryl RT oxidase in adult rat brain."; RL Biochim. Biophys. Acta 1759:225-233(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-200. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ALA-200. RC TISSUE=Chondrosarcoma, and Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10708601; DOI=10.1006/bbrc.2000.2324; RA Coppock D.L., Kopman C., Gudas J., Cina-Poppe D.A.; RT "Regulation of the quiescence-induced genes: quiescin Q6, decorin, and RT ribosomal protein S29."; RL Biochem. Biophys. Res. Commun. 269:604-610(2000). RN [8] RP TISSUE SPECIFICITY. RA Turi G.K.; RT "The distribution and specificity of expression of quiescin Q6 (Q6) in RT Human tissues is associated with both endocrine and non-endocrine protein RT secretion."; RL Proc. Annu. Meet. Am. Assoc. Cancer Res. 42:397-397(2001). RN [9] RP REVIEW, AND NOMENCLATURE. RX PubMed=12176051; DOI=10.1016/s0003-9861(02)00337-5; RA Thorpe C., Hoober K.L., Raje S., Glynn N.M., Burnside J., Turi G.K., RA Coppock D.L.; RT "Sulfhydryl oxidases: emerging catalysts of protein disulfide bond RT formation in eukaryotes."; RL Arch. Biochem. Biophys. 405:1-12(2002). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION. RX PubMed=17331072; DOI=10.1042/bj20061510; RA Chakravarthi S., Jessop C.E., Willer M., Stirling C.J., Bulleid N.J.; RT "Intracellular catalysis of disulfide bond formation by the human RT sulfhydryl oxidase, QSOX1."; RL Biochem. J. 404:403-411(2007). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MUTAGENESIS OF CYS-70; RP CYS-73; CYS-449; CYS-452; CYS-509 AND CYS-512, AND ACTIVE SITE. RX PubMed=18393449; DOI=10.1021/bi702522q; RA Heckler E.J., Alon A., Fass D., Thorpe C.; RT "Human quiescin-sulfhydryl oxidase, QSOX1: probing internal redox steps by RT mutagenesis."; RL Biochemistry 47:4955-4963(2008). RN [13] RP GLYCOSYLATION AT ASN-130. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [14] RP PHOSPHORYLATION AT SER-426. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS RP SPECTROMETRY, ALTERNATIVE SPLICING, MUTAGENESIS OF 70-CYS--CYS-73, AND RP ACTIVE SITE. RX PubMed=23704371; DOI=10.1126/science.1238279; RA Ilani T., Alon A., Grossman I., Horowitz B., Kartvelishvily E., Cohen S.R., RA Fass D.; RT "A secreted disulfide catalyst controls extracellular matrix composition RT and function."; RL Science 341:74-76(2013). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP CATALYTIC ACTIVITY. RX PubMed=26819240; DOI=10.1093/protein/gzv067; RA Grossman I., Ilani T., Fleishman S.J., Fass D.; RT "Overcoming a species-specificity barrier in development of an inhibitory RT antibody targeting a modulator of tumor stroma."; RL Protein Eng. Des. Sel. 29:135-147(2016). RN [18] RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-130 AND RP ASN-243, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF ASN-130; RP ASN-243 AND 276-THR--THR-282. RX PubMed=29757379; DOI=10.1093/glycob/cwy044; RA Horowitz B., Javitt G., Ilani T., Gat Y., Morgenstern D., Bard F.A., RA Fass D.; RT "Quiescin sulfhydryl oxidase 1 (QSOX1) glycosite mutation perturbs RT secretion but not Golgi localization."; RL Glycobiology 28:580-591(2018). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF 70-CYS--CYS-73; HIS-72 AND RP PRO-119, AND ACTIVE SITE. RX PubMed=30367560; DOI=10.1002/pro.3537; RA Javitt G., Grossman-Haham I., Alon A., Resnick E., Mutsafi Y., Ilani T., RA Fass D.; RT "cis-Proline mutants of quiescin sulfhydryl oxidase 1 with altered redox RT properties undermine extracellular matrix integrity and cell adhesion in RT fibroblast cultures."; RL Protein Sci. 28:228-238(2019). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 286-546 IN COMPLEX WITH FAD, RP SUBUNIT, COFACTOR, AND DISULFIDE BONDS. RX PubMed=20211621; DOI=10.1016/j.febslet.2010.03.001; RA Alon A., Heckler E.J., Thorpe C., Fass D.; RT "QSOX contains a pseudo-dimer of functional and degenerate sulfhydryl RT oxidase domains."; RL FEBS Lett. 584:1521-1525(2010). RN [21] {ECO:0007744|PDB:3Q6O} RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 33-272, CATALYTIC ACTIVITY, AND RP DISULFIDE BONDS. RX PubMed=22801504; DOI=10.1038/nature11267; RA Alon A., Grossman I., Gat Y., Kodali V.K., DiMaio F., Mehlman T., Haran G., RA Baker D., Thorpe C., Fass D.; RT "The dynamic disulphide relay of quiescin sulphydryl oxidase."; RL Nature 488:414-418(2012). RN [22] {ECO:0007744|PDB:4IJ3} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 33-272 IN COMPLEX WITH INHIBITORY RP ANTIBODY, FUNCTION, CATALYTIC ACTIVITY, AND DISULFIDE BONDS. RX PubMed=23867277; DOI=10.1016/j.jmb.2013.07.011; RA Grossman I., Alon A., Ilani T., Fass D.; RT "An inhibitory antibody blocks the first step in the dithiol/disulfide RT relay mechanism of the enzyme QSOX1."; RL J. Mol. Biol. 425:4366-4378(2013). CC -!- FUNCTION: Catalyzes the oxidation of sulfhydryl groups in peptide and CC protein thiols to disulfides with the reduction of oxygen to hydrogen CC peroxide (PubMed:17331072, PubMed:18393449, PubMed:23704371, CC PubMed:23867277, PubMed:30367560). Plays a role in disulfide bond CC formation in a variety of extracellular proteins (PubMed:17331072, CC PubMed:22801504, PubMed:23867277, PubMed:30367560). In fibroblasts, CC required for normal incorporation of laminin into the extracellular CC matrix, and thereby for normal cell-cell adhesion and cell migration CC (PubMed:23704371, PubMed:23867277, PubMed:30367560). CC {ECO:0000269|PubMed:17331072, ECO:0000269|PubMed:18393449, CC ECO:0000269|PubMed:22801504, ECO:0000269|PubMed:23704371, CC ECO:0000269|PubMed:23867277, ECO:0000269|PubMed:30367560}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 R'C(R)SH + O2 = R'C(R)S-S(R)CR' + H2O2; CC Xref=Rhea:RHEA:17357, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:16520, ChEBI:CHEBI:17412; EC=1.8.3.2; CC Evidence={ECO:0000269|PubMed:18393449, ECO:0000269|PubMed:22801504, CC ECO:0000269|PubMed:23704371, ECO:0000269|PubMed:23867277, CC ECO:0000269|PubMed:26819240, ECO:0000269|PubMed:29757379, CC ECO:0000269|PubMed:30367560}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:18393449, ECO:0000269|PubMed:20211621}; CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:18393449, CC ECO:0000269|PubMed:20211621}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18393449, CC ECO:0000269|PubMed:20211621}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane CC {ECO:0000269|PubMed:17331072, ECO:0000269|PubMed:23704371}; Single-pass CC membrane protein {ECO:0000305|PubMed:17331072}. Secreted CC {ECO:0000269|PubMed:29757379}. Note=A small proportion is secreted, CC probably via a proteolytic cleavage that removes the membrane anchor. CC {ECO:0000305|PubMed:29757379}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted CC {ECO:0000269|PubMed:10708601}. Note=Found in the extracellular medium CC of quiescent cells but is not found in proliferating cells. CC {ECO:0000269|PubMed:10708601}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=a {ECO:0000303|PubMed:17331072}, QSOX-L CC {ECO:0000303|PubMed:23704371}; CC IsoId=O00391-1; Sequence=Displayed; CC Name=2; Synonyms=b, QSOX-S {ECO:0000303|PubMed:23704371}; CC IsoId=O00391-2; Sequence=VSP_020489, VSP_020490; CC -!- TISSUE SPECIFICITY: Expressed in heart, placenta, lung, liver, skeletal CC muscle, pancreas and very weakly in brain and kidney. CC {ECO:0000269|PubMed:10708601, ECO:0000269|Ref.8}. CC -!- INDUCTION: Induced in quiescent cells just as fibroblasts begin to CC leave the proliferative cycle and enter quiescence. CC {ECO:0000269|PubMed:10708601, ECO:0000269|PubMed:9878249}. CC -!- PTM: N-glycosylated (PubMed:17331072, PubMed:29757379). O-glycosylated CC on Thr and Ser residues (PubMed:29757379). CC {ECO:0000269|PubMed:17331072, ECO:0000269|PubMed:29757379}. CC -!- MISCELLANEOUS: 'Quiescin Q6' means that it was the sixth clone to be CC found at a higher level of expression in quiescent fibroblasts. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the quiescin-sulfhydryl oxidase (QSOX) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92517.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U97276; AAC09010.2; -; mRNA. DR EMBL; AF361868; AAM00263.1; -; mRNA. DR EMBL; AY358941; AAQ89300.1; -; mRNA. DR EMBL; AB209280; BAD92517.1; ALT_INIT; mRNA. DR EMBL; AL390718; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017692; AAH17692.1; -; mRNA. DR EMBL; BC100023; AAI00024.1; -; mRNA. DR CCDS; CCDS1337.1; -. [O00391-1] DR CCDS; CCDS30950.1; -. [O00391-2] DR RefSeq; NP_001004128.1; NM_001004128.2. [O00391-2] DR RefSeq; NP_002817.2; NM_002826.4. [O00391-1] DR PDB; 3LLI; X-ray; 2.05 A; A=286-546. DR PDB; 3LLK; X-ray; 2.00 A; A/B/C=286-546. DR PDB; 3Q6O; X-ray; 2.05 A; A=33-272. DR PDB; 4IJ3; X-ray; 2.70 A; A=33-272. DR PDBsum; 3LLI; -. DR PDBsum; 3LLK; -. DR PDBsum; 3Q6O; -. DR PDBsum; 4IJ3; -. DR AlphaFoldDB; O00391; -. DR SMR; O00391; -. DR BioGRID; 111734; 93. DR IntAct; O00391; 59. DR MINT; O00391; -. DR STRING; 9606.ENSP00000356574; -. DR BindingDB; O00391; -. DR ChEMBL; CHEMBL4523117; -. DR GlyConnect; 1774; 24 N-Linked glycans (4 sites). DR GlyCosmos; O00391; 6 sites, 32 glycans. DR GlyGen; O00391; 22 sites, 32 N-linked glycans (4 sites), 3 O-linked glycans (18 sites). DR iPTMnet; O00391; -. DR PhosphoSitePlus; O00391; -. DR SwissPalm; O00391; -. DR BioMuta; QSOX1; -. DR jPOST; O00391; -. DR MassIVE; O00391; -. DR PaxDb; 9606-ENSP00000356574; -. DR PeptideAtlas; O00391; -. DR PRIDE; O00391; -. DR ProteomicsDB; 47862; -. [O00391-1] DR ProteomicsDB; 47863; -. [O00391-2] DR Pumba; O00391; -. DR ABCD; O00391; 2 sequenced antibodies. DR Antibodypedia; 47086; 206 antibodies from 33 providers. DR DNASU; 5768; -. DR Ensembl; ENST00000367600.5; ENSP00000356572.5; ENSG00000116260.17. [O00391-2] DR Ensembl; ENST00000367602.8; ENSP00000356574.3; ENSG00000116260.17. [O00391-1] DR GeneID; 5768; -. DR KEGG; hsa:5768; -. DR MANE-Select; ENST00000367602.8; ENSP00000356574.3; NM_002826.5; NP_002817.2. DR UCSC; uc001gny.4; human. [O00391-1] DR AGR; HGNC:9756; -. DR CTD; 5768; -. DR DisGeNET; 5768; -. DR GeneCards; QSOX1; -. DR HGNC; HGNC:9756; QSOX1. DR HPA; ENSG00000116260; Low tissue specificity. DR MIM; 603120; gene. DR neXtProt; NX_O00391; -. DR OpenTargets; ENSG00000116260; -. DR PharmGKB; PA162400559; -. DR VEuPathDB; HostDB:ENSG00000116260; -. DR eggNOG; KOG1731; Eukaryota. DR GeneTree; ENSGT00940000159504; -. DR HOGENOM; CLU_020182_1_0_1; -. DR InParanoid; O00391; -. DR OMA; SDMDMRM; -. DR OrthoDB; 20090at2759; -. DR PhylomeDB; O00391; -. DR TreeFam; TF316749; -. DR BRENDA; 1.8.3.2; 2681. DR PathwayCommons; O00391; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; O00391; -. DR BioGRID-ORCS; 5768; 19 hits in 1154 CRISPR screens. DR ChiTaRS; QSOX1; human. DR EvolutionaryTrace; O00391; -. DR GeneWiki; QSOX1; -. DR GenomeRNAi; 5768; -. DR Pharos; O00391; Tbio. DR PRO; PR:O00391; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O00391; protein. DR Bgee; ENSG00000116260; Expressed in stromal cell of endometrium and 200 other cell types or tissues. DR ExpressionAtlas; O00391; baseline and differential. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome. DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0016971; F:flavin-dependent sulfhydryl oxidase activity; IDA:UniProtKB. DR GO; GO:0003756; F:protein disulfide isomerase activity; IDA:UniProtKB. DR GO; GO:0085029; P:extracellular matrix assembly; IMP:UniProtKB. DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:CACAO. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR CDD; cd02992; PDI_a_QSOX; 1. DR FunFam; 1.20.120.1960:FF:000001; Sulfhydryl oxidase; 1. DR FunFam; 1.20.120.310:FF:000001; Sulfhydryl oxidase; 1. DR FunFam; 3.40.30.10:FF:000073; Sulfhydryl oxidase; 1. DR FunFam; 3.40.30.10:FF:000080; Sulfhydryl oxidase; 1. DR Gene3D; 1.20.120.310; ERV/ALR sulfhydryl oxidase domain; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 2. DR Gene3D; 1.20.120.1960; QSOX sulfhydryl oxidase domain; 1. DR InterPro; IPR036774; ERV/ALR_sulphydryl_oxid_sf. DR InterPro; IPR017905; ERV/ALR_sulphydryl_oxidase. DR InterPro; IPR040986; QSOX_FAD-bd_dom. DR InterPro; IPR042568; QSOX_FAD-bd_sf. DR InterPro; IPR041269; QSOX_Trx1. DR InterPro; IPR039798; Sulfhydryl_oxidase. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR013766; Thioredoxin_domain. DR PANTHER; PTHR22897; QUIESCIN Q6-RELATED SULFHYDRYL OXIDASE; 1. DR PANTHER; PTHR22897:SF6; SULFHYDRYL OXIDASE 1; 1. DR Pfam; PF04777; Evr1_Alr; 1. DR Pfam; PF18371; FAD_SOX; 1. DR Pfam; PF18108; QSOX_Trx1; 1. DR Pfam; PF00085; Thioredoxin; 1. DR SUPFAM; SSF69000; FAD-dependent thiol oxidase; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS51324; ERV_ALR; 1. DR PROSITE; PS51352; THIOREDOXIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disulfide bond; FAD; Flavoprotein; KW Glycoprotein; Golgi apparatus; Membrane; Oxidoreductase; Phosphoprotein; KW Proteomics identification; Reference proteome; Secreted; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..29 FT /evidence="ECO:0000255" FT CHAIN 30..747 FT /note="Sulfhydryl oxidase 1" FT /id="PRO_0000249533" FT TRANSMEM 710..730 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 36..156 FT /note="Thioredoxin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT DOMAIN 396..503 FT /note="ERV/ALR sulfhydryl oxidase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654" FT REGION 573..633 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 70 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:30367560" FT ACT_SITE 73 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:30367560" FT BINDING 401 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 408 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 412 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 451 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 455 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 478..485 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 500 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT BINDING 503 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:20211621, FT ECO:0007744|PDB:3LLI, ECO:0007744|PDB:3LLK" FT MOD_RES 426 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:29757379" FT CARBOHYD 243 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29757379" FT CARBOHYD 575 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 70..73 FT /note="Redox-active" FT /evidence="ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:20211621, ECO:0000305|PubMed:23704371, FT ECO:0000305|PubMed:30367560, ECO:0007744|PDB:3LLI, FT ECO:0007744|PDB:3LLK" FT DISULFID 101..110 FT /evidence="ECO:0000269|PubMed:22801504, FT ECO:0000269|PubMed:23867277, ECO:0007744|PDB:3Q6O, FT ECO:0007744|PDB:4IJ3" FT DISULFID 393..405 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621, ECO:0007744|PDB:3LLI, FT ECO:0007744|PDB:3LLK" FT DISULFID 449..452 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621, ECO:0007744|PDB:3LLI, FT ECO:0007744|PDB:3LLK" FT DISULFID 509..512 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621, ECO:0007744|PDB:3LLI, FT ECO:0007744|PDB:3LLK" FT VAR_SEQ 603..604 FT /note="AS -> LI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16806532" FT /id="VSP_020489" FT VAR_SEQ 605..747 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16806532" FT /id="VSP_020490" FT VARIANT 114 FT /note="N -> S (in dbSNP:rs3894211)" FT /id="VAR_027429" FT VARIANT 200 FT /note="G -> A (in dbSNP:rs17855475)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16806532, ECO:0000269|Ref.4" FT /id="VAR_027430" FT VARIANT 256 FT /note="R -> M (in dbSNP:rs4360492)" FT /id="VAR_027431" FT VARIANT 294 FT /note="A -> S (in dbSNP:rs2278943)" FT /id="VAR_027432" FT VARIANT 444 FT /note="H -> R (in dbSNP:rs12371)" FT /evidence="ECO:0000269|PubMed:16806532" FT /id="VAR_027433" FT VARIANT 591 FT /note="N -> H (in dbSNP:rs3738115)" FT /id="VAR_027434" FT VARIANT 605 FT /note="R -> P (in dbSNP:rs16855466)" FT /id="VAR_053652" FT MUTAGEN 70..73 FT /note="CGHC->AGHA: Loss of catalytic activity. Cannot FT prevent cell detachment after depletion of the endogenous FT protein." FT /evidence="ECO:0000269|PubMed:23704371, FT ECO:0000269|PubMed:30367560" FT MUTAGEN 70 FT /note="C->S: Reduces activity by 93%." FT /evidence="ECO:0000269|PubMed:18393449" FT MUTAGEN 72 FT /note="H->A: Decreased protein stability and catalytic FT activity; when associated with S-119 or T-119." FT /evidence="ECO:0000269|PubMed:30367560" FT MUTAGEN 73 FT /note="C->S: Reduces activity by 93%." FT /evidence="ECO:0000269|PubMed:18393449" FT MUTAGEN 119 FT /note="P->S,T: Loss of catalytic activity. Decreased FT protein stability and catalytic activity; when associated FT with A-72." FT /evidence="ECO:0000269|PubMed:30367560" FT MUTAGEN 130 FT /note="N->Q: Loss of glycosylation site." FT /evidence="ECO:0000269|PubMed:29757379" FT MUTAGEN 243 FT /note="N->Q: Loss of glycosylation site. Abolishes FT secretion. No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:29757379" FT MUTAGEN 276..282 FT /note="TTVAPTT->ANVAPVA: Decreased O-glycosylation." FT /evidence="ECO:0000269|PubMed:29757379" FT MUTAGEN 449 FT /note="C->S: Reduces activity by 96%." FT /evidence="ECO:0000269|PubMed:18393449" FT MUTAGEN 452 FT /note="C->S: Loss of activity." FT /evidence="ECO:0000269|PubMed:18393449" FT MUTAGEN 509 FT /note="C->S: No effect. Reduces activity by 70%; when FT associated with S-512." FT /evidence="ECO:0000269|PubMed:18393449" FT MUTAGEN 512 FT /note="C->S: Reduces activity by 40%. Reduces activity by FT 70%; when associated with S-509." FT /evidence="ECO:0000269|PubMed:18393449" FT STRAND 40..45 FT /evidence="ECO:0007829|PDB:3Q6O" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 50..54 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 58..66 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 71..80 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 83..86 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 88..90 FT /evidence="ECO:0007829|PDB:3Q6O" FT TURN 91..93 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 94..100 FT /evidence="ECO:0007829|PDB:3Q6O" FT TURN 104..106 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 107..112 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 117..124 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:4IJ3" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:4IJ3" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 174..177 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 179..182 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 186..193 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 199..206 FT /evidence="ECO:0007829|PDB:3Q6O" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 213..219 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 223..229 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 234..241 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 252..255 FT /evidence="ECO:0007829|PDB:3Q6O" FT HELIX 256..264 FT /evidence="ECO:0007829|PDB:3Q6O" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 301..313 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:3LLK" FT STRAND 320..323 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 324..340 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 345..360 FT /evidence="ECO:0007829|PDB:3LLK" FT STRAND 363..367 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 368..377 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 380..383 FT /evidence="ECO:0007829|PDB:3LLK" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 403..419 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 426..431 FT /evidence="ECO:0007829|PDB:3LLI" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 435..446 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 450..463 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 470..488 FT /evidence="ECO:0007829|PDB:3LLK" FT STRAND 502..504 FT /evidence="ECO:0007829|PDB:3LLK" FT TURN 506..508 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 510..512 FT /evidence="ECO:0007829|PDB:3LLI" FT STRAND 517..519 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 524..534 FT /evidence="ECO:0007829|PDB:3LLK" FT HELIX 537..539 FT /evidence="ECO:0007829|PDB:3LLK" SQ SEQUENCE 747 AA; 82578 MW; 52639D09A50E00C5 CRC64; MRRCNSGSGP PPSLLLLLLW LLAVPGANAA PRSALYSPSD PLTLLQADTV RGAVLGSRSA WAVEFFASWC GHCIAFAPTW KALAEDVKAW RPALYLAALD CAEETNSAVC RDFNIPGFPT VRFFKAFTKN GSGAVFPVAG ADVQTLRERL IDALESHHDT WPPACPPLEP AKLEEIDGFF ARNNEEYLAL IFEKGGSYLG REVALDLSQH KGVAVRRVLN TEANVVRKFG VTDFPSCYLL FRNGSVSRVP VLMESRSFYT AYLQRLSGLT REAAQTTVAP TTANKIAPTV WKLADRSKIY MADLESALHY ILRIEVGRFP VLEGQRLVAL KKFVAVLAKY FPGRPLVQNF LHSVNEWLKR QKRNKIPYSF FKTALDDRKE GAVLAKKVNW IGCQGSEPHF RGFPCSLWVL FHFLTVQAAR QNVDHSQEAA KAKEVLPAIR GYVHYFFGCR DCASHFEQMA AASMHRVGSP NAAVLWLWSS HNRVNARLAG APSEDPQFPK VQWPPRELCS ACHNERLDVP VWDVEATLNF LKAHFSPSNI ILDFPAAGSA ARRDVQNVAA APELAMGALE LESRNSTLDP GKPEMMKSPT NTTPHVPAEG PEASRPPKLH PGLRAAPGQE PPEHMAELQR NEQEQPLGQW HLSKRDTGAA LLAESRAEKN RLWGPLEVRR VGRSSKQLVD IPEGQLEARA GRGRGQWLQV LGGGFSYLDI SLCVGLYSLS FMGLLAMYTY FQAKIRALKG HAGHPAA //