QSOX1_HUMAN
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 03-AUG-2022, entry version 186.
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:30367560, PubMed:23867277). Plays a role in disulfide bond
CC formation in a variety of extracellular proteins (PubMed:17331072,
CC PubMed:30367560, PubMed:22801504, PubMed:23867277). 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:30367560, PubMed:23867277).
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=O2 + 2 R'C(R)SH = H2O2 + R'C(R)S-S(R)CR';
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};
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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; 89.
DR IntAct; O00391; 24.
DR MINT; O00391; -.
DR STRING; 9606.ENSP00000356574; -.
DR BindingDB; O00391; -.
DR ChEMBL; CHEMBL4523117; -.
DR GlyConnect; 1774; 24 N-Linked glycans (4 sites).
DR GlyGen; O00391; 6 sites, 27 N-linked glycans (4 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; O00391; -.
DR PhosphoSitePlus; O00391; -.
DR BioMuta; QSOX1; -.
DR EPD; O00391; -.
DR jPOST; O00391; -.
DR MassIVE; O00391; -.
DR MaxQB; O00391; -.
DR PaxDb; O00391; -.
DR PeptideAtlas; O00391; -.
DR PRIDE; O00391; -.
DR ProteomicsDB; 47862; -. [O00391-1]
DR ProteomicsDB; 47863; -. [O00391-2]
DR ABCD; O00391; 2 sequenced antibodies.
DR Antibodypedia; 47086; 186 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 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; YLWKAHN; -.
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; 17 hits in 1076 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 198 other tissues.
DR ExpressionAtlas; O00391; baseline and differential.
DR Genevisible; O00391; HS.
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:0030173; C:integral component of 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-linked 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 Gene3D; 1.20.120.1960; -; 1.
DR Gene3D; 1.20.120.310; -; 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; PTHR22897; 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; SSF52833; SSF52833; 1.
DR SUPFAM; SSF69000; SSF69000; 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 Reference proteome; Secreted; Signal; 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
