Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Extracellular superoxide dismutase [Cu-Zn]

Gene

SOD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

2 superoxide + 2 H+ = O2 + H2O2.

Cofactori

Protein has several cofactor binding sites:
  • Cu cationBy similarityNote: Binds 1 copper ion per subunit.By similarity
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei41 – 411Not glycated
Sitei92 – 921Not glycated
Metal bindingi114 – 1141Copper; catalytic
Metal bindingi116 – 1161Copper; catalytic
Metal bindingi131 – 1311Copper; catalytic
Metal bindingi131 – 1311Zinc; structural
Metal bindingi139 – 1391Zinc; structural
Metal bindingi142 – 1421Zinc; structural
Metal bindingi145 – 1451Zinc; structural
Metal bindingi181 – 1811Copper; catalytic
Sitei238 – 2381Not glycated

GO - Molecular functioni

  1. copper ion binding Source: GO_Central
  2. heparin binding Source: UniProtKB-KW
  3. superoxide dismutase activity Source: GO_Central
  4. zinc ion binding Source: GO_Central

GO - Biological processi

  1. removal of superoxide radicals Source: GO_Central
  2. response to copper ion Source: Ensembl
  3. response to hypoxia Source: Ensembl
  4. response to reactive oxygen species Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Antioxidant, Oxidoreductase

Keywords - Ligandi

Copper, Heparin-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_264249. Detoxification of Reactive Oxygen Species.

Names & Taxonomyi

Protein namesi
Recommended name:
Extracellular superoxide dismutase [Cu-Zn] (EC:1.15.1.1)
Short name:
EC-SOD
Gene namesi
Name:SOD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:11181. SOD3.

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. extracellular matrix Source: Ensembl
  3. extracellular region Source: Reactome
  4. extracellular space Source: BHF-UCL
  5. extracellular vesicular exosome Source: UniProtKB
  6. Golgi lumen Source: Reactome
  7. nucleus Source: Ensembl
  8. trans-Golgi network Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36018.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Chaini19 – 240222Extracellular superoxide dismutase [Cu-Zn]PRO_0000032855Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi63 ↔ 2081 Publication
Glycosylationi107 – 1071N-linked (GlcNAc...)2 Publications
Disulfide bondi125 ↔ 2071 Publication
Glycosylationi229 – 2291N-linked (Glc) (glycation); in vitro
Glycosylationi230 – 2301N-linked (Glc) (glycation); in vitro

Keywords - PTMi

Disulfide bond, Glycation, Glycoprotein

Proteomic databases

MaxQBiP08294.
PaxDbiP08294.
PeptideAtlasiP08294.
PRIDEiP08294.

PTM databases

PhosphoSiteiP08294.

Miscellaneous databases

PMAP-CutDBP08294.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP08294.
CleanExiHS_SOD3.
ExpressionAtlasiP08294. baseline and differential.
GenevestigatoriP08294.

Organism-specific databases

HPAiHPA042110.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Protein-protein interaction databases

BioGridi112532. 1 interaction.
STRINGi9606.ENSP00000371554.

Structurei

Secondary structure

1
240
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi59 – 679Combined sources
Beta strandi79 – 8810Combined sources
Beta strandi93 – 1008Combined sources
Beta strandi104 – 11714Combined sources
Helixi124 – 1285Combined sources
Beta strandi145 – 1528Combined sources
Beta strandi155 – 16410Combined sources
Beta strandi166 – 1694Combined sources
Beta strandi176 – 1838Combined sources
Beta strandi190 – 1923Combined sources
Helixi195 – 1984Combined sources
Beta strandi204 – 2096Combined sources
Helixi216 – 2227Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JLPX-ray1.70A/B/C/D19-240[»]
ProteinModelPortaliP08294.
SMRiP08294. Positions 55-223.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08294.

Family & Domainsi

Sequence similaritiesi

Belongs to the Cu-Zn superoxide dismutase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG2032.
GeneTreeiENSGT00530000063226.
HOGENOMiHOG000263447.
HOVERGENiHBG000062.
InParanoidiP08294.
KOiK16627.
OMAiHPRHPGD.
PhylomeDBiP08294.
TreeFamiTF105133.

Family and domain databases

Gene3Di2.60.40.200. 1 hit.
InterProiIPR018152. SOD_Cu/Zn_BS.
IPR024141. SOD_Cu/Zn_extracel.
IPR001424. SOD_Cu_Zn_dom.
[Graphical view]
PANTHERiPTHR10003:SF36. PTHR10003:SF36. 1 hit.
PfamiPF00080. Sod_Cu. 1 hit.
[Graphical view]
PRINTSiPR00068. CUZNDISMTASE.
SUPFAMiSSF49329. SSF49329. 1 hit.
PROSITEiPS00087. SOD_CU_ZN_1. 1 hit.
PS00332. SOD_CU_ZN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08294-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM
60 70 80 90 100
QRRDDDGALH AACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE
110 120 130 140 150
GFPTEPNSSS RAIHVHQFGD LSQGCESTGP HYNPLAVPHP QHPGDFGNFA
160 170 180 190 200
VRDGSLWRYR AGLAASLAGP HSIVGRAVVV HAGEDDLGRG GNQASVENGN
210 220 230 240
AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAA
Length:240
Mass (Da):25,851
Last modified:May 30, 2006 - v2
Checksum:i585B8DEBFC506CF4
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581A → T.5 Publications
Corresponds to variant rs2536512 [ dbSNP | Ensembl ].
VAR_020776
Natural varianti91 – 911A → T.1 Publication
Corresponds to variant rs17879876 [ dbSNP | Ensembl ].
VAR_020777
Natural varianti231 – 2311R → G.5 Publications
Corresponds to variant rs1799895 [ dbSNP | Ensembl ].
VAR_014705

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3430.1.
PIRiA28301. DSHUEC.
RefSeqiNP_003093.2. NM_003102.2.
UniGeneiHs.2420.

Genome annotation databases

EnsembliENST00000382120; ENSP00000371554; ENSG00000109610.
GeneIDi6649.
KEGGihsa:6649.
UCSCiuc003gqz.3. human.

Polymorphism databases

DMDMi108885292.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Superoxide dismutase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3430.1.
PIRiA28301. DSHUEC.
RefSeqiNP_003093.2. NM_003102.2.
UniGeneiHs.2420.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JLPX-ray1.70A/B/C/D19-240[»]
ProteinModelPortaliP08294.
SMRiP08294. Positions 55-223.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112532. 1 interaction.
STRINGi9606.ENSP00000371554.

Chemistry

BindingDBiP08294.
ChEMBLiCHEMBL2069159.

PTM databases

PhosphoSiteiP08294.

Polymorphism databases

DMDMi108885292.

Proteomic databases

MaxQBiP08294.
PaxDbiP08294.
PeptideAtlasiP08294.
PRIDEiP08294.

Protocols and materials databases

DNASUi6649.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382120; ENSP00000371554; ENSG00000109610.
GeneIDi6649.
KEGGihsa:6649.
UCSCiuc003gqz.3. human.

Organism-specific databases

CTDi6649.
GeneCardsiGC04P024798.
HGNCiHGNC:11181. SOD3.
HPAiHPA042110.
MIMi185490. gene.
neXtProtiNX_P08294.
PharmGKBiPA36018.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2032.
GeneTreeiENSGT00530000063226.
HOGENOMiHOG000263447.
HOVERGENiHBG000062.
InParanoidiP08294.
KOiK16627.
OMAiHPRHPGD.
PhylomeDBiP08294.
TreeFamiTF105133.

Enzyme and pathway databases

ReactomeiREACT_264249. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

EvolutionaryTraceiP08294.
GeneWikiiSOD3.
GenomeRNAii6649.
NextBioi25915.
PMAP-CutDBP08294.
PROiP08294.
SOURCEiSearch...

Gene expression databases

BgeeiP08294.
CleanExiHS_SOD3.
ExpressionAtlasiP08294. baseline and differential.
GenevestigatoriP08294.

Family and domain databases

Gene3Di2.60.40.200. 1 hit.
InterProiIPR018152. SOD_Cu/Zn_BS.
IPR024141. SOD_Cu/Zn_extracel.
IPR001424. SOD_Cu_Zn_dom.
[Graphical view]
PANTHERiPTHR10003:SF36. PTHR10003:SF36. 1 hit.
PfamiPF00080. Sod_Cu. 1 hit.
[Graphical view]
PRINTSiPR00068. CUZNDISMTASE.
SUPFAMiSSF49329. SSF49329. 1 hit.
PROSITEiPS00087. SOD_CU_ZN_1. 1 hit.
PS00332. SOD_CU_ZN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1986) [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(1993) [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 (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-58.
  4. NIEHS SNPs program
    Submitted (SEP-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(2003) [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(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCATION AT LYS-229 AND LYS-230.
  7. 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(2004) [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(2008) [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(2008) [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(1993) [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(1994) [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(1995) [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(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLY-231.

Entry informationi

Entry nameiSODE_HUMAN
AccessioniPrimary (citable) accession number: P08294
Secondary accession number(s): Q5U781, Q6FHA2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: May 30, 2006
Last modified: April 1, 2015
This is version 167 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.