P08294 (SODE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Extracellular superoxide dismutase [Cu-Zn]
Short name=EC-SOD
EC=1.15.1.1

Gene names

Name:

SOD3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	240 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	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, 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 component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Copper Heparin-binding Metal-binding Zinc
Molecular function	Antioxidant Oxidoreductase
PTM	Disulfide bond Glycation Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	removal of superoxide radicals Inferred from Biological aspect of Ancestor. Source: RefGenome response to copper ion Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular matrix Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL mitochondrion Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome trans-Golgi network Inferred from electronic annotation. Source: Compara
Molecular_function	copper ion binding Inferred from Biological aspect of Ancestor. Source: RefGenome heparin binding Inferred from electronic annotation. Source: UniProtKB-KW 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Chain

19 – 240

222

Extracellular superoxide dismutase [Cu-Zn]

PRO_0000032855

Sites

Metal binding

114

1

Copper; catalytic

Metal binding

116

1

Copper; catalytic

Metal binding

131

1

Copper; catalytic

Metal binding

131

1

Zinc; structural

Metal binding

139

1

Zinc; structural

Metal binding

142

1

Zinc; structural

Metal binding

145

1

Zinc; structural

Metal binding

181

1

Copper; catalytic

Site

41

1

Not glycated

Site

92

1

Not glycated

Site

238

1

Not glycated

Amino acid modifications

Glycosylation

107

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

229

1

N-linked (Glc) (glycation); in vitro Ref.6

Glycosylation

230

1

N-linked (Glc) (glycation); in vitro Ref.6

Disulfide bond

63 ↔ 208

Ref.10

Disulfide bond

125 ↔ 207

Ref.10

Natural variations

Natural variant

58

1

A → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
Corresponds to variant rs2536512 [ dbSNP | Ensembl ].

VAR_020776

Natural variant

91

1

A → T. Ref.4
Corresponds to variant rs17879876 [ dbSNP | Ensembl ].

VAR_020777

Natural variant

231

1

R → G. Ref.4 Ref.11 Ref.12 Ref.13 Ref.14
Corresponds to variant rs1799895 [ dbSNP | Ensembl ].

VAR_014705

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

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.

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.

.

.

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.

.

.

.

.

.

.

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240

Helix Strand Turn

Details...

Beta strand

59 – 67

9

Beta strand

79 – 88

10

Beta strand

93 – 100

8

Beta strand

104 – 117

14

Helix

124 – 128

5

Beta strand

145 – 152

8

Beta strand

155 – 164

10

Beta strand

166 – 169

4

Beta strand

176 – 183

8

Beta strand

190 – 192

3

Helix

195 – 198

4

Beta strand

204 – 209

6

Helix

216 – 222

7

Sequences

	Sequence		Length	Mass (Da)
	P08294 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 585B8DEBFC506CF4	FASTA	240	25,851
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.

IPI

IPI00027827.

PIR

DSHUEC. A28301.

RefSeq

NP_003093.2. NM_003102.2.

UniGene

Hs.2420.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JLP	X-ray	1.70	A/B/C/D	19-240	[»]

ProteinModelPortal

P08294.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000371554.

PTM databases

PhosphoSite

P08294.

Polymorphism databases

DMDM

108885292.

Proteomic databases

PaxDb

P08294.

PeptideAtlas

P08294.

PRIDE

P08294.

Protocols and materials databases

DNASU

6649.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000382120; ENSP00000371554; ENSG00000109610.

GeneID

6649.

KEGG

hsa:6649.

UCSC

uc003gqz.3. human.

Organism-specific databases

CTD

6649.

GeneCards

GC04P024798.

HGNC

HGNC:11181. SOD3.

HPA

CAB008671.

MIM

185490. gene.

neXtProt

NX_P08294.

PharmGKB

PA36018.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2032.

HOGENOM

HOG000263447.

HOVERGEN

HBG000062.

InParanoid

P08294.

KO

K16627.

OMA

CCVIGIC.

OrthoDB

EOG4MCX1S.

PhylomeDB

P08294.

Gene expression databases

Bgee

P08294.

CleanEx

HS_SOD3.

Genevestigator

P08294.

GermOnline

ENSG00000109610. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.200. 1 hit.

InterPro

IPR024134. SOD_Cu/Zn_/chaperones.
IPR018152. SOD_Cu/Zn_BS.
IPR024141. SOD_Cu/Zn_extracel.
IPR001424. SOD_Cu_Zn_dom.
[Graphical view]

PANTHER

PTHR10003. PTHR10003. 1 hit.
PTHR10003:SF10. PTHR10003:SF10. 1 hit.

Pfam

PF00080. Sod_Cu. 1 hit.
[Graphical view]

PRINTS

PR00068. CUZNDISMTASE.

SUPFAM

SSF49329. SOD_Cu_Zn. 1 hit.

PROSITE

PS00087. SOD_CU_ZN_1. 1 hit.
PS00332. SOD_CU_ZN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SOD3. human.

EvolutionaryTrace

P08294.

GenomeRNAi

6649.

NextBio

25915.

PMAP-CutDB

P08294.

SOURCE

Search...

Entry information

Entry name

SODE_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 147 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.