SRXN1_HUMAN
ID SRXN1_HUMAN Reviewed; 137 AA.
AC Q9BYN0; B2R543; Q8NDM3; Q96AK6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Sulfiredoxin-1;
DE EC=1.8.98.2 {ECO:0000269|PubMed:15448164, ECO:0000269|PubMed:15590625};
GN Name=SRXN1; Synonyms=C20orf139, SRX, SRX1;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary cancer;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, Lung, and Uterus;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15448164; DOI=10.1074/jbc.m409482200;
RA Chang T.-S., Jeong W., Woo H.A., Lee S.M., Park S., Rhee S.G.;
RT "Characterization of mammalian sulfiredoxin and its reactivation of
RT hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in
RT the active site to cysteine.";
RL J. Biol. Chem. 279:50994-51001(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-99.
RX PubMed=15590625; DOI=10.1074/jbc.c400496200;
RA Woo H.A., Jeong W., Chang T.-S., Park K.J., Park S.J., Yang J.S.,
RA Rhee S.G.;
RT "Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-cys
RT peroxiredoxins.";
RL J. Biol. Chem. 280:3125-3128(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-11 AND ARG-16, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [11]
RP STRUCTURE BY NMR OF 17-137.
RA Gruschus J.M., Lee D.Y., Ferretti J.A., Rhee S.G.;
RT "Solution structure of human sulfiredoxin (SRX).";
RL Submitted (FEB-2004) to the PDB data bank.
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 32-137 IN COMPLEX WITH ADP.
RX PubMed=15952770; DOI=10.1021/bi050131i;
RA Jonsson T.J., Murray M.S., Johnson L.C., Poole L.B., Lowther W.T.;
RT "Structural basis for the retroreduction of inactivated peroxiredoxins by
RT human sulfiredoxin.";
RL Biochemistry 44:8634-8642(2005).
CC -!- FUNCTION: Contributes to oxidative stress resistance by reducing
CC cysteine-sulfinic acid formed under exposure to oxidants in the
CC peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4 (PubMed:15448164,
CC PubMed:15590625). Does not act on PRDX5 or PRDX6 (PubMed:15448164,
CC PubMed:15590625). May catalyze the reduction in a multi-step process by
CC acting both as a specific phosphotransferase and a thioltransferase
CC (PubMed:15448164, PubMed:15590625). {ECO:0000269|PubMed:15448164,
CC ECO:0000269|PubMed:15590625}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-dithiol + ATP + S-hydroxy-S-oxy-L-cysteinyl-
CC [peroxiredoxin] = [protein]-disulfide + ADP + phosphate + S-hydroxy-
CC L-cysteinyl-[peroxiredoxin]; Xref=Rhea:RHEA:17545, Rhea:RHEA-
CC COMP:10593, Rhea:RHEA-COMP:10594, Rhea:RHEA-COMP:13681, Rhea:RHEA-
CC COMP:17976, ChEBI:CHEBI:29950, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:50058, ChEBI:CHEBI:61973, ChEBI:CHEBI:61974,
CC ChEBI:CHEBI:456216; EC=1.8.98.2;
CC Evidence={ECO:0000269|PubMed:15448164, ECO:0000269|PubMed:15590625};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P36077};
CC -!- INTERACTION:
CC Q9BYN0; Q06830: PRDX1; NbExp=3; IntAct=EBI-15678820, EBI-353193;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15448164}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in kidney,
CC lung, spleen and thymus. {ECO:0000269|PubMed:15448164}.
CC -!- SIMILARITY: Belongs to the sulfiredoxin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SRXN1ID52295ch20p13.html";
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; AK312054; BAG34990.1; -; mRNA.
DR EMBL; AL833944; CAD38799.1; -; mRNA.
DR EMBL; AL121758; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017001; AAH17001.1; -; mRNA.
DR EMBL; BC032604; AAH32604.1; -; mRNA.
DR EMBL; BC047707; AAH47707.1; -; mRNA.
DR CCDS; CCDS13005.1; -.
DR RefSeq; NP_542763.1; NM_080725.2.
DR PDB; 1XW3; X-ray; 1.65 A; A=32-137.
DR PDB; 1XW4; X-ray; 2.00 A; X=32-137.
DR PDB; 1YZS; NMR; -; A=17-137.
DR PDB; 2B6F; NMR; -; A=17-137.
DR PDB; 2RII; X-ray; 2.60 A; X/Y=32-137.
DR PDB; 3CYI; X-ray; 1.80 A; A=32-137.
DR PDB; 3HY2; X-ray; 2.10 A; X/Y=32-137.
DR PDB; 7LJ1; X-ray; 2.97 A; a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t=32-137.
DR PDBsum; 1XW3; -.
DR PDBsum; 1XW4; -.
DR PDBsum; 1YZS; -.
DR PDBsum; 2B6F; -.
DR PDBsum; 2RII; -.
DR PDBsum; 3CYI; -.
DR PDBsum; 3HY2; -.
DR PDBsum; 7LJ1; -.
DR AlphaFoldDB; Q9BYN0; -.
DR BMRB; Q9BYN0; -.
DR SMR; Q9BYN0; -.
DR BioGRID; 126716; 46.
DR CORUM; Q9BYN0; -.
DR DIP; DIP-59836N; -.
DR IntAct; Q9BYN0; 2.
DR STRING; 9606.ENSP00000371388; -.
DR iPTMnet; Q9BYN0; -.
DR PhosphoSitePlus; Q9BYN0; -.
DR BioMuta; SRXN1; -.
DR DMDM; 30315944; -.
DR EPD; Q9BYN0; -.
DR jPOST; Q9BYN0; -.
DR MassIVE; Q9BYN0; -.
DR MaxQB; Q9BYN0; -.
DR PaxDb; Q9BYN0; -.
DR PeptideAtlas; Q9BYN0; -.
DR PRIDE; Q9BYN0; -.
DR ProteomicsDB; 79670; -.
DR Antibodypedia; 69340; 97 antibodies from 30 providers.
DR DNASU; 140809; -.
DR Ensembl; ENST00000381962.4; ENSP00000371388.4; ENSG00000271303.2.
DR GeneID; 140809; -.
DR KEGG; hsa:140809; -.
DR MANE-Select; ENST00000381962.4; ENSP00000371388.4; NM_080725.3; NP_542763.1.
DR UCSC; uc002wea.5; human.
DR CTD; 140809; -.
DR DisGeNET; 140809; -.
DR GeneCards; SRXN1; -.
DR HGNC; HGNC:16132; SRXN1.
DR HPA; ENSG00000271303; Low tissue specificity.
DR MIM; 617583; gene.
DR neXtProt; NX_Q9BYN0; -.
DR OpenTargets; ENSG00000271303; -.
DR PharmGKB; PA25681; -.
DR VEuPathDB; HostDB:ENSG00000271303; -.
DR eggNOG; KOG3388; Eukaryota.
DR GeneTree; ENSGT00390000007832; -.
DR HOGENOM; CLU_124532_1_0_1; -.
DR InParanoid; Q9BYN0; -.
DR OMA; CHRFAAY; -.
DR OrthoDB; 1421270at2759; -.
DR PhylomeDB; Q9BYN0; -.
DR TreeFam; TF300230; -.
DR BRENDA; 1.8.98.2; 2681.
DR PathwayCommons; Q9BYN0; -.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SignaLink; Q9BYN0; -.
DR BioGRID-ORCS; 140809; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; SRXN1; human.
DR EvolutionaryTrace; Q9BYN0; -.
DR GeneWiki; SRXN1; -.
DR GenomeRNAi; 140809; -.
DR Pharos; Q9BYN0; Tbio.
DR PRO; PR:Q9BYN0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BYN0; protein.
DR Bgee; ENSG00000271303; Expressed in islet of Langerhans and 95 other tissues.
DR Genevisible; Q9BYN0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016667; F:oxidoreductase activity, acting on a sulfur group of donors; IDA:UniProtKB.
DR GO; GO:0032542; F:sulfiredoxin activity; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR InterPro; IPR003115; ParB/Sulfiredoxin_dom.
DR InterPro; IPR036086; ParB/Sulfiredoxin_sf.
DR InterPro; IPR016692; Sulfiredoxin.
DR PANTHER; PTHR21348; PTHR21348; 1.
DR Pfam; PF02195; ParBc; 1.
DR PIRSF; PIRSF017267; Sulfiredoxin; 1.
DR SMART; SM00470; ParB; 1.
DR SUPFAM; SSF110849; SSF110849; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; ATP-binding; Cytoplasm; Disulfide bond;
KW Magnesium; Methylation; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..137
FT /note="Sulfiredoxin-1"
FT /id="PRO_0000211431"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98..101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15952770"
FT MOD_RES 11
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 16
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 99
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P36077"
FT MUTAGEN 99
FT /note="C->S: No effect on association with PRDX1, PRDX2,
FT PRDX3 or PRDX4."
FT /evidence="ECO:0000269|PubMed:15590625"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1YZS"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:1YZS"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 59..71
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1XW3"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:1XW3"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 99..107
FT /evidence="ECO:0007829|PDB:1XW3"
FT STRAND 111..120
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 122..129
FT /evidence="ECO:0007829|PDB:1XW3"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:1XW3"
SQ SEQUENCE 137 AA; 14259 MW; 44F2C4256E5574D0 CRC64;
MGLRAGGTLG RAGAGRGAPE GPGPSGGAQG GSIHSGRIAA VHNVPLSVLI RPLPSVLDPA
KVQSLVDTIR EDPDSVPPID VLWIKGAQGG DYFYSFGGCH RYAAYQQLQR ETIPAKLVQS
TLSDLRVYLG ASTPDLQ
