SOD1/YJR104C Summary Help

Standard Name SOD1
Systematic Name YJR104C
Alias CRS4
Feature Type ORF, Verified
Description Cytosolic copper-zinc superoxide dismutase; detoxifies superoxide; stabilizes Yck1p and Yck2p kinases in glucose to repress respiration; phosphorylated by Dun1p and enters the nucleus under oxidative stress to promote transcription of stress response genes; human ortholog implicated in ALS; abundance increases under DNA replication stress and during exposure to boric acid; localization of a fraction to the mitochondrial intermembrane space is modulated by the MICOS complex (1, 2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description SuperOxide Dismutase
Chromosomal Location
ChrX:623014 to 622550 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All SOD1 GO evidence and references
  View Computational GO annotations for SOD1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 19 genes
Classical genetics
Large-scale survey
300 total interaction(s) for 210 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 23
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 3
  • Biochemical Activity: 1
  • Co-crystal Structure: 2
  • Co-purification: 1
  • PCA: 5
  • Reconstituted Complex: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 10
  • Negative Genetic: 99
  • Phenotypic Enhancement: 27
  • Phenotypic Suppression: 12
  • Positive Genetic: 12
  • Synthetic Growth Defect: 28
  • Synthetic Lethality: 42
  • Synthetic Rescue: 27

Expression Summary
Length (a.a.) 154
Molecular Weight (Da) 15,855
Isoelectric Point (pI) 5.93
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:623014 to 622550 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..465 623014..622550 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003865

SOD1 encodes a Cu-Zn superoxide dismutase that plays a role in oxygen radical detoxification and in copper ion buffering. SODs catalyze the breakdown of the superoxide radical, O2-, to an oxygen molecule (dioxygen) and hydrogen peroxide (8, 9). The active form of Sod1p is a homodimer, with each 32kD subunit containing one catalytic copper ion and one zinc ion. Two conserved cysteine residues of each monomer are joined together in a disulfide bond and this bond is critical for enzymatic activity. The specific copper chaperone Ccs1p delivers the copper ion to Sod1p and also facilitates formation of the intramolecular disulfide bond (10). The Cu-Zn-Sod1p is cytosolic; however, a fraction of both Sod1p and its metallochaperone, Ccs1p, localize to the intermembrane space (IMS) of mitochondria where Sod1p performs a physiological role in scavenging mitochondrial reactive oxygen species (ROS). Accumulation of Sod1p within mitochondria is dependent on the presence of the mitochondrial form of Ccs1p, which enhances retention of the immature Sod1p within the IMS (11). S. cerevisiae also synthesizes a Mn-Sod2p, which is mitochondrial.

Null mutations in SOD1 are associated with a number of defects such as sensitivity to oxidative stress, including the inability to grow in aerobic conditions on rich medium, and hypersensitivity to superoxide-generating drugs such as paraquat. Null mutants are also tightly auxotrophic for methionine and lysine and display a leaky leucine auxotrophy, defects considered to result from oxidative damage to relevant metabolic enzymes (12, 13, 14, 15, 16). sod1 null mutants also exhibit mitochondrial defects including poor growth on non-fermentable carbon sources, a deficiency in mitochondrial aconitase, and rapid death in stationary phase.

Increased oxidative damage exhibited by sod1 mutants can be suppressed by mutations or overexpression of several genes. Overexpression of ATX1 or ATX2 or mutation of PMR1 or BSD2 is thought to suppress by altering metal ion homeostasis while overexpression of TKL1 may mediate suppression through enhanced production of NADPH by the pentose phosphate pathway (17). Mutations in SSQ1, JAC1, NFS11 and ISU1 suppress the auxotrophies caused by a sod1 mutations, but do not reverse the sensitivity of sod1delta strains to paraquat (18).

SOD1 and SOD2 are among the first genes to be implicated in the chronological aging of yeast (8, 9, 19). Deletion of SOD1 or both SOD1 and SOD2 dramatically reduces the chronological and replicative life span of yeast (20), while overexpression of both SOD1 and SOD2 extends survival but does not affect metabolic rates (21). Overexpression of SOD1 and CCS1 elevates the levels of Sod1p activity six- to eight-fold in vegetative cultures and increases the survival of stationary phase cells up to two-fold, showing that chronological lifespan is ultimately limited by oxidative stress (22).

Activation of Sod1p in vitro requires both copper-bound Ccs1p and O2 exposure. Transition of anaerobic cultures to aerobic conditions results in the rapid appearance of Sod1p activity. Ccs1p mediates O2 or O-2 responsive activation of apo-Sod1p, thereby playing a direct posttranslational role in controlling the amount of the active form of enzyme (23). Ace1p, a transcriptional activator protein responsible for the induction of metallothionein CUP1, is also responsible for the induction of SOD1 expression in response to copper; the SOD1 promoter contains a single Ace1p binding site (24).

Superoxide dismutases (SODs) are abundant enzymes present in prokaryotes and eukaryotes. Prokaryotes have two forms, one containing iron (Fe) and another containing manganese (Mn). The Cu-Zn form is found in few distantly related bacterial species. Eukaryotes have a Mn-containing form in the mitochondrion and a Cu-Zn containing form in the cytoplasm. The Mn and Fe proteins are related to each other, while the Cu-Zn protein is unrelated to either (9).

Mutations in the human SOD1 are associated with familial Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease, a degenerative disorder of the motor neurons that may be caused by accumulation of reactive oxygen radicals (25, 26, 27, 28).

Last updated: 2007-04-09 Contact SGD

References cited on this page View Complete Literature Guide for SOD1
1) Lyons TJ, et al.  (2000) The metal binding properties of the zinc site of yeast copper-zinc superoxide dismutase: implications for amyotrophic lateral sclerosis. J Biol Inorg Chem 5(2):189-203
2) Saffi J, et al.  (2006) Antioxidant activity of L-ascorbic acid in wild-type and superoxide dismutase deficient strains of Saccharomyces cerevisiae. Redox Rep 11(4):179-84
3) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
4) Schmidt M, et al.  (2012) Role of Hog1, Tps1 and Sod1 in boric acid tolerance of Saccharomyces cerevisiae. Microbiology 158(Pt 10):2667-78
5) Reddi AR and Culotta VC  (2013) SOD1 integrates signals from oxygen and glucose to repress respiration. Cell 152(1-2):224-35
6) Varabyova A, et al.  (2013) Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1. FEBS J 280(20):4943-4959
7) Tsang CK, et al.  (2014) Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun 5():3446
8) Steinman HM  (1980) The amino acid sequence of copper-zinc superoxide dismutase from bakers' yeast. J Biol Chem 255(14):6758-65
9) Bermingham-McDonogh O, et al.  (1988) The copper, zinc-superoxide dismutase gene of Saccharomyces cerevisiae: cloning, sequencing, and biological activity. Proc Natl Acad Sci U S A 85(13):4789-93
10) Furukawa Y, et al.  (2004) Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. EMBO J 23(14):2872-81
11) Sturtz LA, et al.  (2001) A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J Biol Chem 276(41):38084-9
12) Chang EC, et al.  (1991) Genetic and biochemical characterization of Cu,Zn superoxide dismutase mutants in Saccharomyces cerevisiae. J Biol Chem 266(7):4417-24
13) Chang EC and Kosman DJ  (1990) O2-dependent methionine auxotrophy in Cu,Zn superoxide dismutase-deficient mutants of Saccharomyces cerevisiae. J Bacteriol 172(4):1840-5
14) Liu XF, et al.  (1992) Yeast lacking superoxide dismutase. Isolation of genetic suppressors. J Biol Chem 267(26):18298-302
15) Corson LB, et al.  (1999) Oxidative stress and iron are implicated in fragmenting vacuoles of Saccharomyces cerevisiae lacking Cu,Zn-superoxide dismutase. J Biol Chem 274(39):27590-6
16) Wallace MA, et al.  (2004) Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis. Cross-compartment protection by CuZn-superoxide dismutase. J Biol Chem 279(31):32055-62
17) Slekar KH, et al.  (1996) The yeast copper/zinc superoxide dismutase and the pentose phosphate pathway play overlapping roles in oxidative stress protection. J Biol Chem 271(46):28831-6
18) Jensen LT, et al.  (2004) Mutations in Saccharomyces cerevisiae iron-sulfur cluster assembly genes and oxidative stress relevant to Cu,Zn superoxide dismutase. J Biol Chem 279(29):29938-43
19) Culotta VC, et al.  (1995) A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. J Biol Chem 270(50):29991-7
20) Longo VD, et al.  (1996) Superoxide dismutase activity is essential for stationary phase survival in Saccharomyces cerevisiae. Mitochondrial production of toxic oxygen species in vivo. J Biol Chem 271(21):12275-80
21) Fabrizio P and Longo VD  (2003) The chronological life span of Saccharomyces cerevisiae. Aging Cell 2(2):73-81
22) Harris N, et al.  (2005) Overexpressed Sod1p acts either to reduce or to increase the lifespans and stress resistance of yeast, depending on whether it is Cu(2+)-deficient or an active Cu,Zn-superoxide dismutase. Aging Cell 4(1):41-52
23) Brown NM, et al.  (2004) Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase. Proc Natl Acad Sci U S A 101(15):5518-23
24) Gralla EB, et al.  (1991) ACE1, a copper-dependent transcription factor, activates expression of the yeast copper, zinc superoxide dismutase gene. Proc Natl Acad Sci U S A 88(19):8558-62
25) Tamai KT, et al.  (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Proc Natl Acad Sci U S A 90(17):8013-7
26) Nishida CR, et al.  (1994) Characterization of three yeast copper-zinc superoxide dismutase mutants analogous to those coded for in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 91(21):9906-10
27) Corson LB, et al.  (1998) Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants. Proc Natl Acad Sci U S A 95(11):6361-6
28) Gunther MR, et al.  (2004) Expression of a familial amyotrophic lateral sclerosis-associated mutant human superoxide dismutase in yeast leads to decreased mitochondrial electron transport. Arch Biochem Biophys 431(2):207-14