QSOX1_RAT
ID QSOX1_RAT Reviewed; 750 AA.
AC Q6IUU3; Q8K4M2; Q99J80;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Sulfhydryl oxidase 1;
DE Short=rQSOX;
DE Short=rSOx;
DE EC=1.8.3.2 {ECO:0000269|PubMed:11278790, ECO:0000269|PubMed:26819240};
DE AltName: Full=FAD-dependent sulfhydryl oxidase-2;
DE Short=SOx-2;
DE AltName: Full=Quiescin Q6;
DE Flags: Precursor;
GN Name=Qsox1; Synonyms=Qscn6, Sox2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, CATALYTIC ACTIVITY, GLYCOSYLATION, TISSUE SPECIFICITY, COFACTOR,
RP SUBUNIT, AND SUBCELLULAR LOCATION (ISOFORM 3).
RC STRAIN=Wistar; TISSUE=Seminal vesicle;
RX PubMed=11278790; DOI=10.1074/jbc.m010933200;
RA Benayoun B., Esnard-Feve A., Castella S., Courty Y., Esnard F.;
RT "Rat seminal vesicle FAD-dependent sulfhydryl oxidase: biochemical
RT characterization and molecular cloning of a member of the new sulfhydryl
RT oxidase/quiescin Q6 gene family.";
RL J. Biol. Chem. 276:13830-13837(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PROTEIN SEQUENCE OF 33-65,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12354420; DOI=10.1016/s0923-1811(02)00061-0;
RA Matsuba S., Suga Y., Ishidoh K., Hashimoto Y., Takamori K., Kominami E.,
RA Wilhelm B., Seitz J., Ogawa H.;
RT "Sulfhydryl oxidase (SOx) from mouse epidermis: molecular cloning,
RT nucleotide sequence, and expression of recombinant protein in the cultured
RT cells.";
RL J. Dermatol. Sci. 30:50-62(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Wistar; TISSUE=Brain;
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 [4]
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 [5] {ECO:0007744|PDB:4P2L}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 33-550 IN COMPLEX WITH FAD,
RP DISULFIDE BONDS, AND COFACTOR.
RX PubMed=24888638; DOI=10.1002/pro.2496;
RA Gat Y., Vardi-Kilshtain A., Grossman I., Major D.T., Fass D.;
RT "Enzyme structure captures four cysteines aligned for disulfide relay.";
RL Protein Sci. 23:1102-1112(2014).
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:11278790). Plays a role in disulfide bond formation in
CC a variety of extracellular proteins. In fibroblasts, required for
CC normal incorporation of laminin into the extracellular matrix, and
CC thereby for normal cell-cell adhesion and cell migration (By
CC similarity). {ECO:0000250|UniProtKB:O00391,
CC ECO:0000269|PubMed:11278790}.
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:11278790, ECO:0000269|PubMed:26819240};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:11278790};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O00391};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11278790}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O00391}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O00391}. Secreted
CC {ECO:0000250|UniProtKB:O00391}. Note=A small proportion is secreted,
CC probably via a proteolytic cleavage that removes the membrane anchor.
CC {ECO:0000250|UniProtKB:O00391}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC {ECO:0000269|PubMed:11278790, ECO:0000269|PubMed:12354420}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=QSOX-L;
CC IsoId=Q6IUU3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6IUU3-2; Sequence=VSP_020499, VSP_020497, VSP_020498;
CC Name=3;
CC IsoId=Q6IUU3-3; Sequence=VSP_020497, VSP_020498;
CC -!- TISSUE SPECIFICITY: Isoform 3: Detected in seminal vesicle fluid (at
CC protein level) (PubMed:11278790, PubMed:12354420). Isoform 1: Detected
CC in brain, hypophysis, heart, testis and the seminal vesicle. Isoform 3:
CC Highly expressed in the seminal vesicles followed by testis, heart,
CC brain, thymus, hypophysis and lung. Also expressed in prostate, kidney,
CC spleen, liver. {ECO:0000269|PubMed:11278790,
CC ECO:0000269|PubMed:12354420, ECO:0000269|PubMed:16806532}.
CC -!- PTM: N-glycosylated. O-glycosylated on Thr and Ser residues.
CC {ECO:0000250|UniProtKB:O00391}.
CC -!- SIMILARITY: Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.
CC {ECO:0000305}.
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DR EMBL; AF217799; AAM67412.1; -; mRNA.
DR EMBL; AF285078; AAG53892.1; -; mRNA.
DR EMBL; AB044285; BAB21937.1; -; mRNA.
DR EMBL; AY623665; AAT40988.1; -; mRNA.
DR RefSeq; NP_001103368.1; NM_001109898.1. [Q6IUU3-1]
DR RefSeq; NP_445883.1; NM_053431.3. [Q6IUU3-3]
DR PDB; 4P2L; X-ray; 2.90 A; A/B=36-550.
DR PDBsum; 4P2L; -.
DR AlphaFoldDB; Q6IUU3; -.
DR SMR; Q6IUU3; -.
DR STRING; 10116.ENSRNOP00000005052; -.
DR GlyGen; Q6IUU3; 2 sites.
DR PaxDb; Q6IUU3; -.
DR PRIDE; Q6IUU3; -.
DR Ensembl; ENSRNOT00000005052; ENSRNOP00000005052; ENSRNOG00000003649. [Q6IUU3-3]
DR Ensembl; ENSRNOT00000068044; ENSRNOP00000061072; ENSRNOG00000003649. [Q6IUU3-1]
DR GeneID; 84491; -.
DR KEGG; rno:84491; -.
DR UCSC; RGD:68957; rat. [Q6IUU3-1]
DR CTD; 5768; -.
DR RGD; 68957; Qsox1.
DR eggNOG; KOG1731; Eukaryota.
DR GeneTree; ENSGT00940000159504; -.
DR HOGENOM; CLU_020182_1_0_1; -.
DR InParanoid; Q6IUU3; -.
DR OMA; YLWKAHN; -.
DR OrthoDB; 498515at2759; -.
DR PhylomeDB; Q6IUU3; -.
DR BRENDA; 1.8.3.2; 5301.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q6IUU3; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000003649; Expressed in pancreas and 19 other tissues.
DR Genevisible; Q6IUU3; RN.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; ISS:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IEA:Ensembl.
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; ISS:UniProtKB.
DR GO; GO:0085029; P:extracellular matrix assembly; ISO:RGD.
DR GO; GO:0016242; P:negative regulation of macroautophagy; ISO:RGD.
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; Direct protein sequencing;
KW Disulfide bond; FAD; Flavoprotein; Glycoprotein; Golgi apparatus; Membrane;
KW Oxidoreductase; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:11278790,
FT ECO:0000269|PubMed:12354420"
FT CHAIN 33..750
FT /note="Sulfhydryl oxidase 1"
FT /id="PRO_0000249535"
FT TRANSMEM 710..730
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 33..159
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 399..506
FT /note="ERV/ALR sulfhydryl oxidase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654"
FT REGION 545..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 73
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 76
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 404
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT BINDING 411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT BINDING 415
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT BINDING 454
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O00391"
FT BINDING 458
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O00391"
FT BINDING 481..488
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT BINDING 503
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT BINDING 506
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..76
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000255|PROSITE-ProRule:PRU00691,
FT ECO:0000269|PubMed:24888638, ECO:0007744|PDB:4P2L"
FT DISULFID 104..113
FT /evidence="ECO:0000269|PubMed:24888638,
FT ECO:0007744|PDB:4P2L"
FT DISULFID 396..408
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:24888638, ECO:0007744|PDB:4P2L"
FT DISULFID 452..455
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:24888638, ECO:0007744|PDB:4P2L"
FT DISULFID 512..515
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:24888638, ECO:0007744|PDB:4P2L"
FT VAR_SEQ 27..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11278790"
FT /id="VSP_020499"
FT VAR_SEQ 569..570
FT /note="VM -> LL (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11278790,
FT ECO:0000303|PubMed:12354420"
FT /id="VSP_020497"
FT VAR_SEQ 571..750
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11278790,
FT ECO:0000303|PubMed:12354420"
FT /id="VSP_020498"
FT CONFLICT 352
FT /note="N -> S (in Ref. 1; AAM67412)"
FT /evidence="ECO:0000305"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:4P2L"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 61..69
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 74..89
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:4P2L"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 110..115
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 120..127
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 146..157
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:4P2L"
FT TURN 181..185
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 189..196
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:4P2L"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 216..222
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 259..266
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 304..316
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 327..343
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 348..363
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 371..380
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 406..427
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 437..448
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 453..466
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 473..490
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:4P2L"
FT TURN 509..511
FT /evidence="ECO:0007829|PDB:4P2L"
FT STRAND 516..519
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 528..538
FT /evidence="ECO:0007829|PDB:4P2L"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:4P2L"
SQ SEQUENCE 750 AA; 82412 MW; 1781E657ED085114 CRC64;
MRRCGRHSGP PSLLLLLLLL PPLLLSVPGA YAARLSVLYS SSDPLTLLDA DTVRPAVLGS
SSAWAVEFFA SWCGHCIAFA PTWKELANDV KDWRPALNLA VLDCADETNS AVCREFNIAG
FPTVRFFKAF SKNGTGTALP AAGANVQTLR MRLIDALESH RDTWPPACPP LEPAKLKDIN
EFFTRSKAEY LALIFEREDS YLGREVTLDL SQFHAVAVRR VLNSESDVVS KFAVTDFPSC
YLLLRNGSVS RVPVLVESRP FYTSYLRGLP GLTREAPPTT AAPVTPDKIA PTVWKFADRS
KIYMADLESA LHYILRVEVG KFSVLEGQRL VALKKFVAVL AKYFPGQPLV QNFLHSINDW
LQKQQKKKIP YSYFKAALDS RKENAVLAEK VNWIGCQGSE PHFRGFPCSL WVLFHFLTVQ
AHRYSEAHPQ EPADGQEVLQ AMRSYVQSFF GCRDCANHFE QMAAASMHQV KSPSNAVLWL
WTSHNRVNAR LSGALSEDPQ FPKVQWPPRE LCSACHNEVN GQVPLWDLGA TLNFLKAHFS
PANIVRDPPA PGPASRRGTQ DPEASPNLVM DTLKLETGNS VLGHEQAASA ASPGATALDV
PAGKPEASGP QELNAGLSMG GASPGQGPPE HTEELLRDVQ ENAQGQQHLS KRDTEALLLP
EVNHLQGPLA PRRGGHSPKQ LASILEGEPE ALAIQGRRQW LQVLGGGVSF LDISLCVGLY
SVSFMGLLAM YTYFRARMRT PKGHVSYPTA
