SOD2

Protein identityUniProt · HPA

UniProt accession

P04179

Gene

SOD2

Ensembl

ENSG00000291237

Chromosome

6

Canonical length

222 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

222 residues, UniProt reviewed canonical sequence.

>P04179|SOD2
     1  MLSRAVCGTS RQLAPVLGYL GSRQKHSLPD LPYDYGALEP HINAQIMQLH HSKHHAAYVN
    61  NLNVTEEKYQ EALAKGDVTA QIALQPALKF NGGGHINHSI FWTNLSPNGG GEPKGELLEA
   121  IKRDFGSFDK FKEKLTAASV GVQGSGWGWL GFNKERGHLQ IAACPNQDPL QGTTGLIPLL
   181  GIDVWEHAYY LQYKNVRPDY LKAIWNVINW ENVTERYMAC KK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SOD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

1,022 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SOD2.

Disease | AllUniProt

Conditions SOD2 is implicated in, by any mechanism.

• Microvascular complications of diabetes 6 (MVCD6) MIM:612634

Disease | ImmuneIEDB

Conditions an epitope on SOD2 was assayed in.

• type 1 diabetes mellitus T cell

ReferencesPubMed · IEDB

Publications for SOD2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.75

gnomAD pLI

0.15

gnomAD missense Z

0.89

DepMap mean gene effect

-0.7

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to ethanol
• cellular response to oxidative stress
• detection of oxygen
• glutathione metabolic process
• heart development
• hemopoiesis
• hydrogen peroxide biosynthetic process
• intracellular oxygen homeostasis
• intrinsic apoptotic signaling pathway in response to DNA damage
• intrinsic apoptotic signaling pathway in response to oxidative stress
• liver development
• locomotory behavior
• multicellular organismal-level iron ion homeostasis
• negative regulation of cell population proliferation
• negative regulation of fat cell differentiation
• negative regulation of fibroblast proliferation
• negative regulation of membrane hyperpolarization
• negative regulation of neuron apoptotic process
• negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
• negative regulation of vascular associated smooth muscle cell proliferation
• neuron development
• positive regulation of cell migration
• positive regulation of hydrogen peroxide biosynthetic process
• positive regulation of nitric oxide biosynthetic process
• positive regulation of vascular associated smooth muscle cell apoptotic process
• post-embryonic development
• protein homotetramerization
• regulation of blood pressure
• regulation of mitochondrial membrane potential
• regulation of transcription by RNA polymerase II
• release of cytochrome c from mitochondria
• removal of superoxide radicals
• respiratory electron transport chain
• response to activity
• response to axon injury
• response to cadmium ion
• response to electrical stimulus
• response to gamma radiation
• response to hydrogen peroxide
• response to hyperoxia
• response to hypoxia
• response to immobilization stress
• response to isolation stress
• response to L-ascorbic acid
• response to lipopolysaccharide
• response to manganese ion
• response to selenium ion
• response to silicon dioxide
• response to superoxide
• response to xenobiotic stimulus
• response to zinc ion
• superoxide anion generation
• superoxide metabolic process
• acetylcholine-mediated vasodilation involved in regulation of systemic arterial blood pressure
• erythrophore differentiation
• positive regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching
• response to magnetism

Molecular functions

• DNA binding
• enzyme binding
• identical protein binding
• manganese ion binding
• oxygen binding
• superoxide dismutase activity

Cellular components

• extracellular exosome
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Manganese/iron superoxide dismutase
• Manganese/iron superoxide dismutase, N-terminal
• Manganese/iron superoxide dismutase, C-terminal
• Manganese/iron superoxide dismutase, binding site
• Manganese/iron superoxide dismutase, C-terminal domain superfamily
• Manganese/iron superoxide dismutase, N-terminal domain superfamily
• Iron/Manganese Superoxide Dismutase
• Iron/manganese superoxide dismutases, alpha-hairpin domain
• Iron/manganese superoxide dismutases, C-terminal domain

KeywordsUniProt

• Acetylation
• Manganese
• Metal-binding
• Mitochondrion
• Nitration
• Oxidoreductase
• Transit peptide
• Ubl conjugation