SODE_HUMAN
ID SODE_HUMAN Reviewed; 240 AA.
AC P08294; Q5U781; Q6FHA2;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Extracellular superoxide dismutase [Cu-Zn];
DE Short=EC-SOD;
DE EC=1.15.1.1;
DE Flags: Precursor;
GN Name=SOD3;
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], PARTIAL PROTEIN SEQUENCE, AND VARIANT THR-58.
RX PubMed=3476950; DOI=10.1073/pnas.84.18.6340;
RA Hjalmarsson K., Marklund S.L., Engstroem A., Edlund T.;
RT "Isolation and sequence of complementary DNA encoding human extracellular
RT superoxide dismutase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6340-6344(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-58.
RC TISSUE=Blood;
RX PubMed=7959763; DOI=10.1006/geno.1994.1357;
RA Folz R.J., Crapo J.D.;
RT "Extracellular superoxide dismutase (SOD3): tissue-specific expression,
RT genomic characterization, and computer-assisted sequence analysis of the
RT human EC SOD gene.";
RL Genomics 22:162-171(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-58.
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-58; THR-91 AND GLY-231.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-58.
RC TISSUE=Colon;
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 [6]
RP GLYCATION AT LYS-229 AND LYS-230.
RX PubMed=1505778; DOI=10.1016/0891-5849(92)90016-a;
RA Adachi T., Ohta H., Hayashi K., Hirano K., Marklund S.L.;
RT "The site of nonenzymic glycation of human extracellular-superoxide
RT dismutase in vitro.";
RL Free Radic. Biol. Med. 13:205-210(1992).
RN [7]
RP REVIEW.
RX PubMed=16087389; DOI=10.1016/j.biocel.2005.06.012;
RA Nozik-Grayck E., Suliman H.B., Piantadosi C.A.;
RT "Extracellular superoxide dismutase.";
RL Int. J. Biochem. Cell Biol. 37:2466-2471(2005).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107.
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 [9]
RP INTERACTION WITH SOD3.
RX PubMed=16371425; DOI=10.1096/fj.05-4564fje;
RA Qin Z., Itoh S., Jeney V., Ushio-Fukai M., Fukai T.;
RT "Essential role for the Menkes ATPase in activation of extracellular
RT superoxide dismutase: implication for vascular oxidative stress.";
RL FASEB J. 20:334-336(2006).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 19-240, SUBUNIT, METAL-BINDING
RP SITES, AND DISULFIDE BONDS.
RX PubMed=19289127; DOI=10.1016/j.jmb.2009.03.026;
RA Antonyuk S.V., Strange R.W., Marklund S.L., Hasnain S.S.;
RT "The structure of human extracellular copper-zinc superoxide dismutase at
RT 1.7 A resolution: insights into heparin and collagen binding.";
RL J. Mol. Biol. 388:310-326(2009).
RN [12]
RP VARIANT GLY-231.
RX PubMed=8034674; DOI=10.1016/s0021-9258(17)32289-5;
RA Sandstrom J., Nilsson P., Karlsson K., Marklund S.L.;
RT "10-fold increase in human plasma extracellular superoxide dismutase
RT content caused by a mutation in heparin-binding domain.";
RL J. Biol. Chem. 269:19163-19166(1994).
RN [13]
RP VARIANT GLY-231.
RX PubMed=7662997; DOI=10.1007/bf01883574;
RA Yamada H., Yamada Y., Adachi T., Goto H., Ogasawara N., Futenma A.,
RA Kitano M., Hirano K., Kato K.;
RT "Molecular analysis of extracellular-superoxide dismutase gene associated
RT with high level in serum.";
RL Jpn. J. Hum. Genet. 40:177-184(1995).
RN [14]
RP VARIANT GLY-231.
RX PubMed=8546689; DOI=10.1042/bj3130235;
RA Adachi T., Yamada H., Yamada Y., Morihara N., Yamazaki N., Murakami T.,
RA Futenma A., Kato K., Hirano K.;
RT "Substitution of glycine for arginine-213 in extracellular-superoxide
RT dismutase impairs affinity for heparin and endothelial cell surface.";
RL Biochem. J. 313:235-239(1996).
RN [15]
RP VARIANT GLY-231.
RX PubMed=8864862; DOI=10.1093/oxfordjournals.jbchem.a021383;
RA Adachi T., Morihara N., Yamazaki N., Yamada H., Futenma A., Kato K.,
RA Hirano K.;
RT "An arginine-213 to glycine mutation in human extracellular-superoxide
RT dismutase reduces susceptibility to trypsin-like proteinases.";
RL J. Biochem. 120:184-188(1996).
CC -!- FUNCTION: Protect the extracellular space from toxic effect of reactive
CC oxygen intermediates by converting superoxide radicals into hydrogen
CC peroxide and oxygen.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:18421; EC=1.15.1.1;
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000250};
CC Note=Binds 1 copper ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homotetramer (PubMed:19289127). Directly interacts with ATP7A;
CC this interaction is copper-dependent and is required for SOD3 activity
CC (PubMed:16371425). {ECO:0000269|PubMed:16371425,
CC ECO:0000269|PubMed:19289127}.
CC -!- INTERACTION:
CC P08294; Q12797-6: ASPH; NbExp=3; IntAct=EBI-10195782, EBI-12092171;
CC P08294; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-10195782, EBI-22452746;
CC P08294; Q9Y2W7: KCNIP3; NbExp=6; IntAct=EBI-10195782, EBI-751501;
CC P08294; O43765: SGTA; NbExp=3; IntAct=EBI-10195782, EBI-347996;
CC P08294; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-10195782, EBI-744081;
CC P08294; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-10195782, EBI-741480;
CC P08294; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-10195782, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. Golgi apparatus,
CC trans-Golgi network {ECO:0000250|UniProtKB:O09164}. Note=99% of EC-SOD
CC is anchored to heparan sulfate proteoglycans in the tissue
CC interstitium, and 1% is located in the vasculature in equilibrium
CC between the plasma and the endothelium.
CC -!- TISSUE SPECIFICITY: Expressed in blood vessels, heart, lung, kidney and
CC placenta. Major SOD isoenzyme in extracellular fluids such as plasma,
CC lymph and synovial fluid.
CC -!- POLYMORPHISM: The variant Gly-231 which is found in about 2.2% of
CC individual displays a 10-fold increased plasma EC-SOD content due to
CC reduced heparin-binding affinity and thus the impairment of its binding
CC ability to endothelial cell surface. {ECO:0000269|PubMed:7662997,
CC ECO:0000269|PubMed:8034674, ECO:0000269|PubMed:8546689}.
CC -!- SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/sod3/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Superoxide dismutase entry;
CC URL="https://en.wikipedia.org/wiki/Superoxide_dismutase";
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; J02947; AAA66000.1; -; mRNA.
DR EMBL; U10116; AAA62278.1; -; Genomic_DNA.
DR EMBL; CR541853; CAG46651.1; -; mRNA.
DR EMBL; AY787834; AAV40827.1; -; Genomic_DNA.
DR EMBL; BC014418; AAH14418.1; -; mRNA.
DR CCDS; CCDS3430.1; -.
DR PIR; A28301; DSHUEC.
DR RefSeq; NP_003093.2; NM_003102.2.
DR PDB; 2JLP; X-ray; 1.70 A; A/B/C/D=19-240.
DR PDBsum; 2JLP; -.
DR AlphaFoldDB; P08294; -.
DR SMR; P08294; -.
DR BioGRID; 112532; 10.
DR IntAct; P08294; 7.
DR STRING; 9606.ENSP00000371554; -.
DR BindingDB; P08294; -.
DR ChEMBL; CHEMBL2069159; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR GlyConnect; 1233; 3 N-Linked glycans (1 site).
DR GlyGen; P08294; 2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P08294; -.
DR PhosphoSitePlus; P08294; -.
DR BioMuta; SOD3; -.
DR DMDM; 108885292; -.
DR EPD; P08294; -.
DR jPOST; P08294; -.
DR MassIVE; P08294; -.
DR MaxQB; P08294; -.
DR PaxDb; P08294; -.
DR PeptideAtlas; P08294; -.
DR PRIDE; P08294; -.
DR ProteomicsDB; 52104; -.
DR Antibodypedia; 3278; 578 antibodies from 36 providers.
DR DNASU; 6649; -.
DR Ensembl; ENST00000382120.4; ENSP00000371554.3; ENSG00000109610.6.
DR GeneID; 6649; -.
DR KEGG; hsa:6649; -.
DR MANE-Select; ENST00000382120.4; ENSP00000371554.3; NM_003102.4; NP_003093.2.
DR UCSC; uc003gqz.4; human.
DR CTD; 6649; -.
DR DisGeNET; 6649; -.
DR GeneCards; SOD3; -.
DR HGNC; HGNC:11181; SOD3.
DR HPA; ENSG00000109610; Tissue enhanced (choroid).
DR MIM; 185490; gene.
DR neXtProt; NX_P08294; -.
DR OpenTargets; ENSG00000109610; -.
DR PharmGKB; PA36018; -.
DR VEuPathDB; HostDB:ENSG00000109610; -.
DR eggNOG; KOG0441; Eukaryota.
DR GeneTree; ENSGT00940000162224; -.
DR HOGENOM; CLU_056632_3_1_1; -.
DR InParanoid; P08294; -.
DR OMA; MHAKITE; -.
DR OrthoDB; 1574423at2759; -.
DR PhylomeDB; P08294; -.
DR TreeFam; TF105133; -.
DR BioCyc; MetaCyc:HS03242-MON; -.
DR BRENDA; 1.15.1.1; 2681.
DR PathwayCommons; P08294; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR SignaLink; P08294; -.
DR BioGRID-ORCS; 6649; 11 hits in 1073 CRISPR screens.
DR ChiTaRS; SOD3; human.
DR EvolutionaryTrace; P08294; -.
DR GeneWiki; SOD3; -.
DR GenomeRNAi; 6649; -.
DR Pharos; P08294; Tbio.
DR PRO; PR:P08294; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P08294; protein.
DR Bgee; ENSG00000109610; Expressed in descending thoracic aorta and 148 other tissues.
DR ExpressionAtlas; P08294; baseline and differential.
DR Genevisible; P08294; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0004784; F:superoxide dismutase activity; IBA:GO_Central.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IBA:GO_Central.
DR GO; GO:0046688; P:response to copper ion; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR CDD; cd00305; Cu-Zn_Superoxide_Dismutase; 1.
DR DisProt; DP02656; -.
DR Gene3D; 2.60.40.200; -; 1.
DR InterPro; IPR024141; EC-SOD.
DR InterPro; IPR036423; SOD-like_Cu/Zn_dom_sf.
DR InterPro; IPR024134; SOD_Cu/Zn_/chaperone.
DR InterPro; IPR018152; SOD_Cu/Zn_BS.
DR InterPro; IPR001424; SOD_Cu_Zn_dom.
DR PANTHER; PTHR10003; PTHR10003; 1.
DR PANTHER; PTHR10003:SF77; PTHR10003:SF77; 1.
DR Pfam; PF00080; Sod_Cu; 1.
DR PRINTS; PR00068; CUZNDISMTASE.
DR SUPFAM; SSF49329; SSF49329; 1.
DR PROSITE; PS00087; SOD_CU_ZN_1; 1.
DR PROSITE; PS00332; SOD_CU_ZN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Copper; Direct protein sequencing;
KW Disulfide bond; Glycation; Glycoprotein; Golgi apparatus; Heparin-binding;
KW Metal-binding; Oxidoreductase; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..18
FT CHAIN 19..240
FT /note="Extracellular superoxide dismutase [Cu-Zn]"
FT /id="PRO_0000032855"
FT BINDING 114
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 116
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 131
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT BINDING 181
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT SITE 41
FT /note="Not glycated"
FT SITE 92
FT /note="Not glycated"
FT SITE 238
FT /note="Not glycated"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 229
FT /note="N-linked (Glc) (glycation) lysine; in vitro"
FT /evidence="ECO:0000269|PubMed:1505778"
FT CARBOHYD 230
FT /note="N-linked (Glc) (glycation) lysine; in vitro"
FT /evidence="ECO:0000269|PubMed:1505778"
FT DISULFID 63..208
FT /evidence="ECO:0000269|PubMed:19289127"
FT DISULFID 125..207
FT /evidence="ECO:0000269|PubMed:19289127"
FT VARIANT 58
FT /note="A -> T (in dbSNP:rs2536512)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:3476950, ECO:0000269|PubMed:7959763,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.4"
FT /id="VAR_020776"
FT VARIANT 91
FT /note="A -> T (in dbSNP:rs17879876)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020777"
FT VARIANT 231
FT /note="R -> G (in dbSNP:rs1799895)"
FT /evidence="ECO:0000269|PubMed:7662997,
FT ECO:0000269|PubMed:8034674, ECO:0000269|PubMed:8546689,
FT ECO:0000269|PubMed:8864862, ECO:0000269|Ref.4"
FT /id="VAR_014705"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 79..88
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 104..117
FT /evidence="ECO:0007829|PDB:2JLP"
FT HELIX 124..128
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 155..164
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 176..183
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2JLP"
FT HELIX 195..198
FT /evidence="ECO:0007829|PDB:2JLP"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:2JLP"
FT HELIX 216..222
FT /evidence="ECO:0007829|PDB:2JLP"
SQ SEQUENCE 240 AA; 25851 MW; 585B8DEBFC506CF4 CRC64;
MLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGALH
AACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGD
LSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVV
HAGEDDLGRG GNQASVENGN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAA
