Extracellular superoxide dismutase [Cu-Zn] precursor

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P08294 (SODE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 133. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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
Cellular component	extracellular space Inferred from direct assay. Source: BHF-UCL nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome soluble fraction Traceable author statement. Source: ProtInc
Molecular function	copper 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. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

Chain

19 – 240

222

Extracellular superoxide dismutase [Cu-Zn]

PRO_0000032855

Sites

Metal binding

114

Copper; catalytic

Metal binding

116

Copper; catalytic

Metal binding

131

Copper; catalytic

Metal binding

131

Zinc; structural

Metal binding

139

Zinc; structural

Metal binding

142

Zinc; structural

Metal binding

145

Zinc; structural

Metal binding

181

Copper; catalytic

Site

Not glycated

Site

Not glycated

Site

238

Not glycated

Amino acid modifications

Glycosylation

107

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

Glycosylation

229

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

Glycosylation

230

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

Disulfide bond

Disulfide bond

Natural variations

Natural variant

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

VAR_020776

Natural variant

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

VAR_020777

Natural variant

231

R → 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

Length

Mass (Da)

Tools

P08294 [UniParc].

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

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

« Hide

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: 3476950] [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: 7959763] [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: 15489334] [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: 1505778] [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: 16087389] [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: 16335952] [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: 19159218] [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: 19289127] [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: 8034674] [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: 7662997] [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: 8546689] [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: 8864862] [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.

SMR

P08294. Positions 55-223.

ModBase

Search...

Protein-protein interaction databases

STRING

P08294.

Polymorphism databases

DMDM

108885292.

Proteomic databases

PeptideAtlas

P08294.

PRIDE

P08294.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000382120; ENSP00000371554; ENSG00000109610.

GeneID

6649.

KEGG

hsa:6649.

UCSC

uc003gqz.1. human.

Organism-specific databases

CTD

6649.

GeneCards

GC04P024798.

H-InvDB

HIX0004137.

HGNC

HGNC:11181. SOD3.

HPA

CAB008671.

MIM

185490. gene.

neXtProt

NX_P08294.

PharmGKB

PA36018.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14694.

HOGENOM

HBG609879.

HOVERGEN

HBG000062.

InParanoid

P08294.

OMA

HPRHPGD.

OrthoDB

EOG4MCX1S.

PhylomeDB

P08294.

Gene expression databases

ArrayExpress

P08294.

Bgee

P08294.

CleanEx

HS_SOD3.

Genevestigator

P08294.

GermOnline

ENSG00000109610. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:2.60.40.200. SOD_Cu_Zn. 1 hit.

K00518.

PANTHER

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

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:	January 25, 2012
This is version 133 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.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents