[1]	NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT THR-58. PubMed=3476950 [NCBI, ExPASy, EBI, Israel, Japan] Hjalmarsson K., Marklund S.L., Engstroem A., Edlund T.; "Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase."; Proc. Natl. Acad. Sci. U.S.A. 84:6340-6344(1987).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-58. TISSUE=Blood; DOI=10.1006/geno.1994.1357; PubMed=7959763 [NCBI, ExPASy, EBI, Israel, Japan] Folz R.J., Crapo J.D.; "Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC SOD gene."; Genomics 22:162-171(1994).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-58. 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.; "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."; Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-58; THR-91 AND GLY-231. Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Chambers S.W., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A.; "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-58. TISSUE=Colon; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[6]	GLYCATION AT LYS-229 AND LYS-230. DOI=10.1016/0891-5849(92)90016-A; PubMed=1505778 [NCBI, ExPASy, EBI, Israel, Japan] Adachi T., Ohta H., Hayashi K., Hirano K., Marklund S.L.; "The site of nonenzymic glycation of human extracellular-superoxide dismutase in vitro."; Free Radic. Biol. Med. 13:205-210(1992).
[7]	REVIEW. DOI=10.1016/j.biocel.2005.06.012; PubMed=16087389 [NCBI, ExPASy, EBI, Israel, Japan] Nozik-Grayck E., Suliman H.B., Piantadosi C.A.; "Extracellular superoxide dismutase."; Int. J. Biochem. Cell Biol. 37:2466-2471(2005).
[8]	GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107, AND MASS SPECTROMETRY. TISSUE=Plasma; DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan] Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.; "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."; J. Proteome Res. 4:2070-2080(2005).
[9]	VARIANT GLY-231. PubMed=8034674 [NCBI, ExPASy, EBI, Israel, Japan] Sandstrom J., Nilsson P., Karlsson K., Marklund S.L.; "10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain."; J. Biol. Chem. 269:19163-19166(1994).
[10]	VARIANT GLY-231. PubMed=7662997 [NCBI, ExPASy, EBI, Israel, Japan] Yamada H., Yamada Y., Adachi T., Goto H., Ogasawara N., Futenma A., Kitano M., Hirano K., Kato K.; "Molecular analysis of extracellular-superoxide dismutase gene associated with high level in serum."; Jpn. J. Hum. Genet. 40:177-184(1995).
[11]	VARIANT GLY-231. PubMed=8546689 [NCBI, ExPASy, EBI, Israel, Japan] Adachi T., Yamada H., Yamada Y., Morihara N., Yamazaki N., Murakami T., Futenma A., Kato K., Hirano K.; "Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface."; Biochem. J. 313:235-239(1996).
[12]	VARIANT GLY-231. PubMed=8864862 [NCBI, ExPASy, EBI, Israel, Japan] Adachi T., Morihara N., Yamazaki N., Yamada H., Futenma A., Kato K., Hirano K.; "An arginine-213 to glycine mutation in human extracellular-superoxide dismutase reduces susceptibility to trypsin-like proteinases."; J. Biochem. 120:184-188(1996).

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).
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: Homotetramer.
SUBCELLULAR LOCATION: Secreted, extracellular 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, lungs, 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.
SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family.
WEB RESOURCE: Name=Wikipedia; Note=Superoxide dismutase entry; URL="http://en.wikipedia.org/wiki/Superoxide_dismutase";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

J02947; AAA66000.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U10116; AAA62278.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CR541853; CAG46651.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY787834; AAV40827.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC014418; AAH14418.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A28301; DSHUEC.

NP_003093.2; -.

3D structure databases

HSSP

P00441; 1OZU. [HSSP ENTRY / PDB]

ModBase

P08294.

Polymorphism databases

NIEHS-SNPs

SOD3.

Organism-specific databases

HIX0004137; -.

HGNC:11181; SOD3.

CAB008671; -.

185490; gene. [NCBI / EBI]

PharmGKB

PA36018; -.

GeneCards

P08294.

Gene expression databases

ArrayExpress

P08294; -.

CleanEx

HS_SOD3; -.

GermOnline

ENSG00000109610; Homo sapiens.

Ontologies

GO:0005625;	Cellular component: soluble fraction (traceable author statement from ProtInc).
GO:0004784;	Molecular function: superoxide dismutase activity (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR001424; SOD_Cu_Zn.
Graphical view of domain structure.

Gene3D

G3DSA:2.60.40.200; SOD_Cu_Zn; 1.

PANTHER

PTHR10003; SOD_Cu_Zn; 1.

Pfam

PF00080; Sod_Cu; 1.
Pfam graphical view of domain structure.

PRINTS

PR00068; CUZNDISMTASE.

ProDom

PD000469; SOD_CU_ZN; 1.
[Domain structure / List of seq. sharing at least 1 domain]

PROSITE

PS00087; SOD_CU_ZN_1; 1.
PS00332; SOD_CU_ZN_2; 1.

BLOCKS

P08294.

Proteomic databases

PeptideAtlas

P08294; -.

Genome annotation databases

Ensembl

ENSG00000109610; Homo sapiens. [Contig view]

GeneID

6649; -.

KEGG

hsa:6649; -.

Phylogenomic databases

HOGENOM

P08294; -.

HOVERGEN

P08294; -.

Other

SOD3; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Antioxidant; Copper; Direct protein sequencing; Glycation; Glycoprotein; Heparin-binding; Metal-binding; Oxidoreductase; Polymorphism; Secreted; Signal; Zinc.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 18`	`18`
`CHAIN`	`19 240`	`222`	`Extracellular superoxide dismutase [Cu-Zn].`	`PRO_0000032855`
`METAL`	`114 114`		`Copper; catalytic (By similarity).`
`METAL`	`116 116`		`Copper; catalytic (By similarity).`
`METAL`	`131 131`		`Copper; catalytic (By similarity).`
`METAL`	`131 131`		`Zinc; structural (By similarity).`
`METAL`	`139 139`		`Zinc; structural (By similarity).`
`METAL`	`142 142`		`Zinc; structural (By similarity).`
`METAL`	`145 145`		`Zinc; structural (By similarity).`
`METAL`	`181 181`		`Copper; catalytic (By similarity).`
`SITE`	`41 41`	`1`	`Not glycated.`
`SITE`	`92 92`	`1`	`Not glycated.`
`SITE`	`238 238`	`1`	`Not glycated.`
`CARBOHYD`	`107 107`		`N-linked (GlcNAc...).`
`CARBOHYD`	`229 229`		`N-linked (Glc) (glycation); in vitro.`
`CARBOHYD`	`230 230`		`N-linked (Glc) (glycation); in vitro.`
`DISULFID`	`125 207`		`By similarity.`
`VARIANT`	`58 58`	`1`	`A -> T (in dbSNP:rs2536512 [NCBI]).`	`VAR_020776`
`VARIANT`	`91 91`	`1`	`A -> T (in dbSNP:rs17879876 [NCBI]).`	`VAR_020777`
`VARIANT`	`231 231`	`1`	`R -> G (in dbSNP:rs1799895 [NCBI]).`	`VAR_014705`

Sequence information

Length: 240 AA [This is the length of the unprocessed precursor]

Molecular weight: 25851 Da [This is the MW of the unprocessed precursor]

CRC64: 585B8DEBFC506CF4 [This is a checksum on the sequence]

        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

P08294 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools