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P08294 (SODE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Extracellular superoxide dismutase [Cu-Zn]

Short name=EC-SOD
EC=1.15.1.1
Gene names
Name:SOD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length240 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen.

Catalytic activity

2 superoxide + 2 H+ = O2 + H2O2.

Cofactor

Binds 1 copper ion per subunit By similarity.

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Homotetramer. Ref.10

Subcellular location

Secretedextracellular space. Note: 99% of EC-SOD is anchored to heparan sulfate proteoglycans in the tissue interstitium, and 1% is located in the vasculature in equilibrium between the plasma and the endothelium.

Tissue specificity

Expressed in blood vessels, heart, lung, kidney and placenta. Major SOD isoenzyme in extracellular fluids such as plasma, lymph and synovial fluid.

Polymorphism

The variant Gly-231 which is found in about 2.2% of individual displays a 10-fold increased plasma EC-SOD content due to reduced heparin-binding affinity and thus the impairment of its binding ability to endothelial cell surface.

Sequence similarities

Belongs to the Cu-Zn superoxide dismutase family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandCopper
Heparin-binding
Metal-binding
Zinc
   Molecular functionAntioxidant
Oxidoreductase
   PTMDisulfide bond
Glycation
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processremoval of superoxide radicals

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to copper ion

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular matrix

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 20551380. Source: BHF-UCL

nucleus

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncopper ion binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15528465. Source: BHF-UCL

superoxide dismutase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

zinc ion binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818
Chain19 – 240222Extracellular superoxide dismutase [Cu-Zn]
PRO_0000032855

Sites

Metal binding1141Copper; catalytic
Metal binding1161Copper; catalytic
Metal binding1311Copper; catalytic
Metal binding1311Zinc; structural
Metal binding1391Zinc; structural
Metal binding1421Zinc; structural
Metal binding1451Zinc; structural
Metal binding1811Copper; catalytic
Site411Not glycated
Site921Not glycated
Site2381Not glycated

Amino acid modifications

Glycosylation1071N-linked (GlcNAc...) Ref.8 Ref.9
Glycosylation2291N-linked (Glc) (glycation); in vitro Ref.6
Glycosylation2301N-linked (Glc) (glycation); in vitro Ref.6
Disulfide bond63 ↔ 208 Ref.10
Disulfide bond125 ↔ 207 Ref.10

Natural variations

Natural variant581A → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
Corresponds to variant rs2536512 [ dbSNP | Ensembl ].
VAR_020776
Natural variant911A → T. Ref.4
Corresponds to variant rs17879876 [ dbSNP | Ensembl ].
VAR_020777
Natural variant2311R → G. Ref.4 Ref.11 Ref.12 Ref.13 Ref.14
Corresponds to variant rs1799895 [ dbSNP | Ensembl ].
VAR_014705

Secondary structure

........................... 240
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08294 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: 585B8DEBFC506CF4

FASTA24025,851
        10         20         30         40         50         60 
MLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGALH 

        70         80         90        100        110        120 
AACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGD 

       130        140        150        160        170        180 
LSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVV 

       190        200        210        220        230        240 
HAGEDDLGRG GNQASVENGN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAA 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase."
Hjalmarsson K., Marklund S.L., Engstroem A., Edlund T.
Proc. Natl. Acad. Sci. U.S.A. 84:6340-6344(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT THR-58.
[2]"Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC SOD gene."
Folz R.J., Crapo J.D.
Genomics 22:162-171(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-58.
Tissue: Blood.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-58.
[4]NIEHS SNPs program
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-58; THR-91 AND GLY-231.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-58.
Tissue: Colon.
[6]"The site of nonenzymic glycation of human extracellular-superoxide dismutase in vitro."
Adachi T., Ohta H., Hayashi K., Hirano K., Marklund S.L.
Free Radic. Biol. Med. 13:205-210(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCATION AT LYS-229 AND LYS-230.
[7]"Extracellular superoxide dismutase."
Nozik-Grayck E., Suliman H.B., Piantadosi C.A.
Int. J. Biochem. Cell Biol. 37:2466-2471(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107.
Tissue: Plasma.
[9]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107.
Tissue: Liver.
[10]"The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding."
Antonyuk S.V., Strange R.W., Marklund S.L., Hasnain S.S.
J. Mol. Biol. 388:310-326(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 19-240, SUBUNIT, METAL-BINDING SITES, DISULFIDE BONDS.
[11]"10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain."
Sandstrom J., Nilsson P., Karlsson K., Marklund S.L.
J. Biol. Chem. 269:19163-19166(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-231.
[12]"Molecular analysis of extracellular-superoxide dismutase gene associated with high level in serum."
Yamada H., Yamada Y., Adachi T., Goto H., Ogasawara N., Futenma A., Kitano M., Hirano K., Kato K.
Jpn. J. Hum. Genet. 40:177-184(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-231.
[13]"Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface."
Adachi T., Yamada H., Yamada Y., Morihara N., Yamazaki N., Murakami T., Futenma A., Kato K., Hirano K.
Biochem. J. 313:235-239(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-231.
[14]"An arginine-213 to glycine mutation in human extracellular-superoxide dismutase reduces susceptibility to trypsin-like proteinases."
Adachi T., Morihara N., Yamazaki N., Yamada H., Futenma A., Kato K., Hirano K.
J. Biochem. 120:184-188(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-231.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Superoxide dismutase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02947 mRNA. Translation: AAA66000.1.
U10116 Genomic DNA. Translation: AAA62278.1.
CR541853 mRNA. Translation: CAG46651.1.
AY787834 Genomic DNA. Translation: AAV40827.1.
BC014418 mRNA. Translation: AAH14418.1.
CCDSCCDS3430.1.
PIRDSHUEC. A28301.
RefSeqNP_003093.2. NM_003102.2.
UniGeneHs.2420.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JLPX-ray1.70A/B/C/D19-240[»]
ProteinModelPortalP08294.
SMRP08294. Positions 55-223.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000371554.

Chemistry

ChEMBLCHEMBL2069159.

PTM databases

PhosphoSiteP08294.

Polymorphism databases

DMDM108885292.

Proteomic databases

MaxQBP08294.
PaxDbP08294.
PeptideAtlasP08294.
PRIDEP08294.

Protocols and materials databases

DNASU6649.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382120; ENSP00000371554; ENSG00000109610.
GeneID6649.
KEGGhsa:6649.
UCSCuc003gqz.3. human.

Organism-specific databases

CTD6649.
GeneCardsGC04P024798.
HGNCHGNC:11181. SOD3.
HPACAB008671.
MIM185490. gene.
neXtProtNX_P08294.
PharmGKBPA36018.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2032.
HOGENOMHOG000263447.
HOVERGENHBG000062.
InParanoidP08294.
KOK16627.
OMAHPRHPGD.
PhylomeDBP08294.
TreeFamTF105133.

Enzyme and pathway databases

ReactomeREACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressP08294.
BgeeP08294.
CleanExHS_SOD3.
GenevestigatorP08294.

Family and domain databases

Gene3D2.60.40.200. 1 hit.
InterProIPR018152. SOD_Cu/Zn_BS.
IPR024141. SOD_Cu/Zn_extracel.
IPR001424. SOD_Cu_Zn_dom.
[Graphical view]
PANTHERPTHR10003:SF36. PTHR10003:SF36. 1 hit.
PfamPF00080. Sod_Cu. 1 hit.
[Graphical view]
PRINTSPR00068. CUZNDISMTASE.
SUPFAMSSF49329. SSF49329. 1 hit.
PROSITEPS00087. SOD_CU_ZN_1. 1 hit.
PS00332. SOD_CU_ZN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSOD3. human.
EvolutionaryTraceP08294.
GeneWikiSOD3.
GenomeRNAi6649.
NextBio25915.
PMAP-CutDBP08294.
PROP08294.
SOURCESearch...

Entry information

Entry nameSODE_HUMAN
AccessionPrimary (citable) accession number: P08294
Secondary accession number(s): Q5U781, Q6FHA2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM