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 08-MAY-2019, entry version 166. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT families: thioredoxin and ERV1."; RL Genomics 54:460-468(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ALA-200 AND RP 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., RA Mairet-Coello G., Esnard-Feve A., Fellmann D., Jouvenot M.; RT "Identification and expression of a new splicing variant of FAD- RT sulfhydryl 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RT project: 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 RT protein 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., RA Moore R.J., 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 RP CYS-70; CYS-73; CYS-449; CYS-452; CYS-509 AND CYS-512, AND ACTIVE RP 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 RT steps by 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., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated 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 RT phosphoproteome."; RL Cell 161:1619-1632(2015). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION BY RP MASS SPECTROMETRY, ALTERNATIVE SPLICING, MUTAGENESIS OF RP 70-CYS--CYS-73, AND ACTIVE SITE. RX PubMed=23704371; DOI=10.1126/science.1238279; RA Ilani T., Alon A., Grossman I., Horowitz B., Kartvelishvily E., RA Cohen S.R., Fass D.; RT "A secreted disulfide catalyst controls extracellular matrix RT composition 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., RA Ayoub D., 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 RT inhibitory 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 RP ASN-130; 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 RP AND 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., RA Ilani T., Fass D.; RT "cis-Proline mutants of quiescin sulfhydryl oxidase 1 with altered RT redox properties undermine extracellular matrix integrity and cell RT adhesion in 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:0000244|PDB:3Q6O} RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 33-272, CATALYTIC ACTIVITY, RP AND DISULFIDE BONDS. RX PubMed=22801504; DOI=10.1038/nature11267; RA Alon A., Grossman I., Gat Y., Kodali V.K., DiMaio F., Mehlman T., RA Haran G., Baker D., Thorpe C., Fass D.; RT "The dynamic disulphide relay of quiescin sulphydryl oxidase."; RL Nature 488:414-418(2012). RN [22] {ECO:0000244|PDB:4IJ3} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 33-272 IN COMPLEX WITH RP INHIBITORY ANTIBODY, FUNCTION, CATALYTIC ACTIVITY, AND DISULFIDE RP 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 CC and protein thiols to disulfides with the reduction of oxygen to CC hydrogen peroxide (PubMed:17331072, PubMed:18393449, CC PubMed:23704371, PubMed:30367560, PubMed:23867277). Plays a role CC in disulfide bond formation in a variety of extracellular proteins CC (PubMed:17331072, PubMed:30367560, PubMed:22801504, CC PubMed:23867277). In fibroblasts, required for normal CC incorporation of laminin into the extracellular matrix, and CC 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, CC ECO:0000269|PubMed:22801504, ECO:0000269|PubMed:23704371, CC ECO:0000269|PubMed:23867277, ECO:0000269|PubMed:26819240, CC ECO:0000269|PubMed:29757379, ECO:0000269|PubMed:30367560}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:18393449, CC 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}; CC Single-pass membrane protein {ECO:0000305|PubMed:17331072}. CC Secreted {ECO:0000269|PubMed:29757379}. Note=A small proportion is CC secreted, probably via a proteolytic cleavage that removes the CC membrane anchor. {ECO:0000305|PubMed:29757379}. CC -!- SUBCELLULAR LOCATION: Isoform 2: Secreted CC {ECO:0000269|PubMed:10708601}. Note=Found in the extracellular CC medium 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, CC skeletal 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- CC glycosylated 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 CC be found at a higher level of expression in quiescent fibroblasts. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the quiescin-sulfhydryl oxidase (QSOX) CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92517.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; 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 SMR; O00391; -. DR BioGrid; 111734; 21. DR IntAct; O00391; 11. DR MINT; O00391; -. DR STRING; 9606.ENSP00000356574; -. DR GlyConnect; 1774; -. DR iPTMnet; O00391; -. DR PhosphoSitePlus; O00391; -. DR BioMuta; QSOX1; -. DR EPD; O00391; -. DR jPOST; O00391; -. DR MaxQB; O00391; -. DR PaxDb; O00391; -. DR PeptideAtlas; O00391; -. DR PRIDE; O00391; -. DR ProteomicsDB; 47862; -. DR ProteomicsDB; 47863; -. [O00391-2] DR DNASU; 5768; -. DR Ensembl; ENST00000367600; ENSP00000356572; ENSG00000116260. [O00391-2] DR Ensembl; ENST00000367602; ENSP00000356574; ENSG00000116260. [O00391-1] DR GeneID; 5768; -. DR KEGG; hsa:5768; -. DR UCSC; uc001gny.4; human. [O00391-1] DR CTD; 5768; -. DR DisGeNET; 5768; -. DR GeneCards; QSOX1; -. DR HGNC; HGNC:9756; QSOX1. DR HPA; HPA042127; -. DR HPA; HPA056243; -. DR MIM; 603120; gene. DR neXtProt; NX_O00391; -. DR OpenTargets; ENSG00000116260; -. DR PharmGKB; PA162400559; -. DR eggNOG; KOG1731; Eukaryota. DR eggNOG; ENOG410XVJT; LUCA. DR GeneTree; ENSGT00940000159504; -. DR HOGENOM; HOG000231631; -. DR InParanoid; O00391; -. DR KO; K10758; -. DR OMA; KNFFGCT; -. DR OrthoDB; 498515at2759; -. DR PhylomeDB; O00391; -. DR TreeFam; TF316749; -. DR BRENDA; 1.8.3.2; 2681. 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 ChiTaRS; QSOX1; human. DR EvolutionaryTrace; O00391; -. DR GeneWiki; QSOX1; -. DR GenomeRNAi; 5768; -. DR PRO; PR:O00391; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000116260; Expressed in 227 organ(s), highest expression level in right testis. 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: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:0016971; F:flavin-linked sulfhydryl oxidase activity; IDA:UniProtKB. DR GO; GO:0003756; F:protein disulfide isomerase activity; IDA:UniProtKB. DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:CACAO. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. 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; 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; Complete proteome; Disulfide bond; KW FAD; Flavoprotein; Glycoprotein; Golgi apparatus; Membrane; KW Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome; KW Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 29 {ECO:0000255}. FT CHAIN 30 747 Sulfhydryl oxidase 1. FT /FTId=PRO_0000249533. FT TRANSMEM 710 730 Helical. {ECO:0000255}. FT DOMAIN 36 156 Thioredoxin. {ECO:0000255|PROSITE- FT ProRule:PRU00691}. FT DOMAIN 396 503 ERV/ALR sulfhydryl oxidase. FT {ECO:0000255|PROSITE-ProRule:PRU00654}. FT NP_BIND 478 485 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT ACT_SITE 70 70 Nucleophile. FT {ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:30367560}. FT ACT_SITE 73 73 Nucleophile. FT {ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:30367560}. FT BINDING 401 401 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 408 408 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 412 412 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 451 451 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 455 455 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 500 500 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT BINDING 503 503 FAD. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000269|PubMed:20211621}. FT MOD_RES 426 426 Phosphoserine; by FAM20C. FT {ECO:0000269|PubMed:26091039}. FT CARBOHYD 130 130 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:29757379}. FT CARBOHYD 243 243 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:29757379}. FT CARBOHYD 575 575 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 70 73 Redox-active. {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000305|PubMed:18393449, FT ECO:0000305|PubMed:20211621, FT ECO:0000305|PubMed:23704371, FT ECO:0000305|PubMed:30367560}. FT DISULFID 101 110 {ECO:0000244|PDB:3Q6O, FT ECO:0000244|PDB:4IJ3, FT ECO:0000269|PubMed:22801504, FT ECO:0000269|PubMed:23867277}. FT DISULFID 393 405 {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621}. FT DISULFID 449 452 {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621}. FT DISULFID 509 512 {ECO:0000244|PDB:3LLI, FT ECO:0000244|PDB:3LLK, FT ECO:0000255|PROSITE-ProRule:PRU00654, FT ECO:0000269|PubMed:20211621}. FT VAR_SEQ 603 604 AS -> LI (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16806532}. FT /FTId=VSP_020489. FT VAR_SEQ 605 747 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16806532}. FT /FTId=VSP_020490. FT VARIANT 114 114 N -> S (in dbSNP:rs3894211). FT /FTId=VAR_027429. FT VARIANT 200 200 G -> A (in dbSNP:rs17855475). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16806532, FT ECO:0000269|Ref.4}. FT /FTId=VAR_027430. FT VARIANT 256 256 R -> M (in dbSNP:rs4360492). FT /FTId=VAR_027431. FT VARIANT 294 294 A -> S (in dbSNP:rs2278943). FT /FTId=VAR_027432. FT VARIANT 444 444 H -> R (in dbSNP:rs12371). FT {ECO:0000269|PubMed:16806532}. FT /FTId=VAR_027433. FT VARIANT 591 591 N -> H (in dbSNP:rs3738115). FT /FTId=VAR_027434. FT VARIANT 605 605 R -> P (in dbSNP:rs16855466). FT /FTId=VAR_053652. FT MUTAGEN 70 73 CGHC->AGHA: Loss of catalytic activity. FT Cannot prevent cell detachment after FT depletion of the endogenous protein. FT {ECO:0000269|PubMed:23704371, FT ECO:0000269|PubMed:30367560}. FT MUTAGEN 70 70 C->S: Reduces activity by 93%. FT {ECO:0000269|PubMed:18393449}. FT MUTAGEN 72 72 H->A: Decreased protein stability and FT catalytic activity; when associated with FT S-119 or T-119. FT {ECO:0000269|PubMed:30367560}. FT MUTAGEN 73 73 C->S: Reduces activity by 93%. FT {ECO:0000269|PubMed:18393449}. FT MUTAGEN 119 119 P->S,T: Loss of catalytic activity. FT Decreased protein stability and catalytic FT activity; when associated with A-72. FT {ECO:0000269|PubMed:30367560}. FT MUTAGEN 130 130 N->Q: Loss of glycosylation site. FT {ECO:0000269|PubMed:29757379}. FT MUTAGEN 243 243 N->Q: Loss of glycosylation site. FT Abolishes secretion. No effect on FT catalytic activity. FT {ECO:0000269|PubMed:29757379}. FT MUTAGEN 276 282 TTVAPTT->ANVAPVA: Decreased O- FT glycosylation. FT {ECO:0000269|PubMed:29757379}. FT MUTAGEN 449 449 C->S: Reduces activity by 96%. FT {ECO:0000269|PubMed:18393449}. FT MUTAGEN 452 452 C->S: Loss of activity. FT {ECO:0000269|PubMed:18393449}. FT MUTAGEN 509 509 C->S: No effect. Reduces activity by 70%; FT when associated with S-512. FT {ECO:0000269|PubMed:18393449}. FT MUTAGEN 512 512 C->S: Reduces activity by 40%. Reduces FT activity by 70%; when associated with S- FT 509. {ECO:0000269|PubMed:18393449}. FT STRAND 40 45 {ECO:0000244|PDB:3Q6O}. FT TURN 47 49 {ECO:0000244|PDB:3Q6O}. FT HELIX 50 54 {ECO:0000244|PDB:3Q6O}. FT STRAND 58 66 {ECO:0000244|PDB:3Q6O}. FT HELIX 71 80 {ECO:0000244|PDB:3Q6O}. FT HELIX 83 86 {ECO:0000244|PDB:3Q6O}. FT HELIX 88 90 {ECO:0000244|PDB:3Q6O}. FT TURN 91 93 {ECO:0000244|PDB:3Q6O}. FT STRAND 94 100 {ECO:0000244|PDB:3Q6O}. FT TURN 104 106 {ECO:0000244|PDB:3Q6O}. FT HELIX 107 112 {ECO:0000244|PDB:3Q6O}. FT STRAND 117 124 {ECO:0000244|PDB:3Q6O}. FT STRAND 130 132 {ECO:0000244|PDB:4IJ3}. FT STRAND 134 136 {ECO:0000244|PDB:4IJ3}. FT HELIX 143 155 {ECO:0000244|PDB:3Q6O}. FT HELIX 174 177 {ECO:0000244|PDB:3Q6O}. FT HELIX 179 182 {ECO:0000244|PDB:3Q6O}. FT STRAND 186 193 {ECO:0000244|PDB:3Q6O}. FT HELIX 199 206 {ECO:0000244|PDB:3Q6O}. FT TURN 207 209 {ECO:0000244|PDB:3Q6O}. FT STRAND 213 219 {ECO:0000244|PDB:3Q6O}. FT HELIX 223 229 {ECO:0000244|PDB:3Q6O}. FT STRAND 234 241 {ECO:0000244|PDB:3Q6O}. FT STRAND 246 248 {ECO:0000244|PDB:3Q6O}. FT STRAND 252 255 {ECO:0000244|PDB:3Q6O}. FT HELIX 256 264 {ECO:0000244|PDB:3Q6O}. FT STRAND 298 300 {ECO:0000244|PDB:3LLK}. FT HELIX 301 313 {ECO:0000244|PDB:3LLK}. FT HELIX 316 318 {ECO:0000244|PDB:3LLK}. FT STRAND 320 323 {ECO:0000244|PDB:3LLK}. FT HELIX 324 340 {ECO:0000244|PDB:3LLK}. FT HELIX 345 360 {ECO:0000244|PDB:3LLK}. FT STRAND 363 367 {ECO:0000244|PDB:3LLK}. FT HELIX 368 377 {ECO:0000244|PDB:3LLK}. FT HELIX 380 383 {ECO:0000244|PDB:3LLK}. FT STRAND 400 402 {ECO:0000244|PDB:3LLK}. FT HELIX 403 419 {ECO:0000244|PDB:3LLK}. FT HELIX 426 431 {ECO:0000244|PDB:3LLI}. FT HELIX 432 434 {ECO:0000244|PDB:3LLK}. FT HELIX 435 446 {ECO:0000244|PDB:3LLK}. FT HELIX 450 463 {ECO:0000244|PDB:3LLK}. FT HELIX 464 466 {ECO:0000244|PDB:3LLK}. FT HELIX 470 488 {ECO:0000244|PDB:3LLK}. FT STRAND 502 504 {ECO:0000244|PDB:3LLK}. FT TURN 506 508 {ECO:0000244|PDB:3LLK}. FT HELIX 510 512 {ECO:0000244|PDB:3LLI}. FT STRAND 517 519 {ECO:0000244|PDB:3LLK}. FT HELIX 524 534 {ECO:0000244|PDB:3LLK}. FT HELIX 537 539 {ECO:0000244|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 //