RBCC Red Blood Cell Collection

CCS [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Copper chaperone for superoxide dismutase (Superoxide dismutase copper chaperone)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00021389
IPI00021389 Copper chaperone for superoxide dismutase Superoxide dismutase copper chaperone, Delivers copper to copper zinc superoxide dismutase (SOD1), copper binding soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt O14618
ID CCS_HUMAN Reviewed; 274 AA.
AC O14618; Q2M366;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Copper chaperone for superoxide dismutase;
DE AltName: Full=Superoxide dismutase copper chaperone;
GN Name=CCS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9295278; DOI=10.1074/jbc.272.38.23469;
RA Culotta V.C., Klomp L.W., Strain J., Casareno R.L.B., Krems B.,
RA Gitlin J.D.;
RT "The copper chaperone for superoxide dismutase.";
RL J. Biol. Chem. 272:23469-23472(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=9726962; DOI=10.1074/jbc.273.37.23625;
RA Casareno R.L.B., Waggoner D., Gitlin J.D.;
RT "The copper chaperone CCS directly interacts with copper/zinc
RT superoxide dismutase.";
RL J. Biol. Chem. 273:23625-23628(1998).
RN [5]
RP MUTAGENESIS OF CYS-22; CYS-25; CYS-244 AND CYS-246, AND METAL-BINDING.
RX PubMed=15736924; DOI=10.1021/bi0478392;
RA Stasser J.P., Eisses J.F., Barry A.N., Kaplan J.H., Blackburn N.J.;
RT "Cysteine-to-serine mutants of the human copper chaperone for
RT superoxide dismutase reveal a copper cluster at a domain III dimer
RT interface.";
RL Biochemistry 44:3143-3152(2005).
RN [6]
RP INTERACTION WITH COMMD1.
RX PubMed=20595380; DOI=10.1074/jbc.M110.101477;
RA Vonk W.I., Wijmenga C., Berger R., van de Sluis B., Klomp L.W.;
RT "Cu,Zn superoxide dismutase maturation and activity are regulated by
RT COMMD1.";
RL J. Biol. Chem. 285:28991-29000(2010).
RN [7]
RP UBIQUITINATION AT LYS-76; LYS-189; LYS-216 AND LYS-241 BY XIAP/BIRC4,
RP AND INTERACTION WITH XIAP/BIRC4.
RX PubMed=20154138; DOI=10.1128/MCB.00900-09;
RA Brady G.F., Galban S., Liu X., Basrur V., Gitlin J.D.,
RA Elenitoba-Johnson K.S., Wilson T.E., Duckett C.S.;
RT "Regulation of the copper chaperone CCS by XIAP-mediated
RT ubiquitination.";
RL Mol. Cell. Biol. 30:1923-1936(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INTERACTION WITH SOD1, VARIANT TRP-163, AND CHARACTERIZATION OF
RP VARIANT TRP-163.
RX PubMed=22508683; DOI=10.1002/humu.22099;
RA Huppke P., Brendel C., Korenke G.C., Marquardt I., Donsante A., Yi L.,
RA Hicks J.D., Steinbach P.J., Wilson C., Elpeleg O., Moller L.B.,
RA Christodoulou J., Kaler S.G., Gartner J.;
RT "Molecular and biochemical characterization of a unique mutation in
RT CCS, the human copper chaperone to superoxide dismutase.";
RL Hum. Mutat. 33:1207-1215(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 84-237 IN COMPLEX WITH ZINC,
RP SUBUNIT, AND DISULFIDE BOND.
RX PubMed=10677207; DOI=10.1021/bi992822i;
RA Lamb A.L., Wernimont A.K., Pufahl R.A., O'Halloran T.V.,
RA Rosenzweig A.C.;
RT "Crystal structure of the second domain of the human copper chaperone
RT for superoxide dismutase.";
RL Biochemistry 39:1589-1595(2000).
RN [11]
RP STRUCTURE BY NMR OF 1-87.
RG RIKEN structural genomics initiative (RSGI);
RT "The apo form of HMA domain of copper chaperone for superoxide
RT dismutase.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Delivers copper to copper zinc superoxide dismutase
CC (SOD1).
CC -!- COFACTOR: Binds 2 copper ions per subunit.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Homodimer, and heterodimer with SOD1. Interacts with
CC COMMD1. Interacts with XIAP/BIRC4.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Ubiquitinion by XIAP/BIRC4 leads to enhancement of its
CC chaperone activity toward its physiologic target, SOD1, rather
CC than proteasomal degradation. XIAP/BIRC4 preferentially
CC ubiquitinates at Lys-241.
CC -!- SIMILARITY: In the C-terminal section; belongs to the Cu-Zn
CC superoxide dismutase family.
CC -!- SIMILARITY: Contains 1 HMA domain.
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DR EMBL; AF002210; AAC51764.1; -; mRNA.
DR EMBL; CR541928; CAG46726.1; -; mRNA.
DR EMBL; BC105016; AAI05017.1; -; mRNA.
DR EMBL; BC112055; AAI12056.1; -; mRNA.
DR RefSeq; NP_005116.1; NM_005125.1.
DR UniGene; Hs.502917; -.
DR PDB; 1DO5; X-ray; 2.75 A; A/B/C/D=84-237.
DR PDB; 2CRL; NMR; -; A=1-85.
DR PDB; 2RSQ; NMR; -; A=1-85.
DR PDBsum; 1DO5; -.
DR PDBsum; 2CRL; -.
DR PDBsum; 2RSQ; -.
DR ProteinModelPortal; O14618; -.
DR SMR; O14618; 9-79, 84-237.
DR MINT; MINT-153485; -.
DR STRING; 9606.ENSP00000307870; -.
DR PhosphoSite; O14618; -.
DR OGP; O14618; -.
DR PaxDb; O14618; -.
DR PRIDE; O14618; -.
DR DNASU; 9973; -.
DR Ensembl; ENST00000533244; ENSP00000436318; ENSG00000173992.
DR GeneID; 9973; -.
DR KEGG; hsa:9973; -.
DR UCSC; uc001oir.3; human.
DR CTD; 9973; -.
DR GeneCards; GC11P066360; -.
DR HGNC; HGNC:1613; CCS.
DR HPA; CAB008672; -.
DR MIM; 603864; gene.
DR neXtProt; NX_O14618; -.
DR PharmGKB; PA26177; -.
DR eggNOG; COG2032; -.
DR HOGENOM; HOG000263450; -.
DR HOVERGEN; HBG018933; -.
DR InParanoid; O14618; -.
DR KO; K04569; -.
DR OMA; WEERDRP; -.
DR OrthoDB; EOG776SR4; -.
DR PhylomeDB; O14618; -.
DR EvolutionaryTrace; O14618; -.
DR GeneWiki; CCS_(gene); -.
DR GenomeRNAi; 9973; -.
DR NextBio; 37666; -.
DR PRO; PR:O14618; -.
DR ArrayExpress; O14618; -.
DR Bgee; O14618; -.
DR CleanEx; HS_CCS; -.
DR Genevestigator; O14618; -.
DR GO; GO:0005829; C:cytosol; IBA:RefGenome.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0004784; F:superoxide dismutase activity; IBA:RefGenome.
DR GO; GO:0016532; F:superoxide dismutase copper chaperone activity; IBA:RefGenome.
DR GO; GO:0008270; F:zinc ion binding; IBA:RefGenome.
DR GO; GO:0015680; P:intracellular copper ion transport; IBA:RefGenome.
DR GO; GO:0051353; P:positive regulation of oxidoreductase activity; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IBA:RefGenome.
DR Gene3D; 2.60.40.200; -; 1.
DR InterPro; IPR006121; HeavyMe-assoc_HMA.
DR InterPro; IPR024134; SOD_Cu/Zn_/chaperone.
DR InterPro; IPR018152; SOD_Cu/Zn_BS.
DR InterPro; IPR001424; SOD_Cu_Zn_dom.
DR PANTHER; PTHR10003; PTHR10003; 1.
DR Pfam; PF00403; HMA; 1.
DR Pfam; PF00080; Sod_Cu; 1.
DR PRINTS; PR00068; CUZNDISMTASE.
DR SUPFAM; SSF49329; SSF49329; 1.
DR SUPFAM; SSF55008; SSF55008; 1.
DR PROSITE; PS01047; HMA_1; FALSE_NEG.
DR PROSITE; PS50846; HMA_2; 1.
DR PROSITE; PS00087; SOD_CU_ZN_1; FALSE_NEG.
DR PROSITE; PS00332; SOD_CU_ZN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Complete proteome; Copper; Cytoplasm;
KW Disulfide bond; Isopeptide bond; Metal-binding; Polymorphism;
KW Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1 274 Copper chaperone for superoxide
FT dismutase.
FT /FTId=PRO_0000213543.
FT DOMAIN 12 75 HMA.
FT REGION 88 234 Superoxide dismutase-like.
FT METAL 22 22 Copper 1.
FT METAL 25 25 Copper 1.
FT METAL 147 147 Zinc.
FT METAL 155 155 Zinc.
FT METAL 164 164 Zinc.
FT METAL 167 167 Zinc.
FT METAL 244 244 Copper 2.
FT METAL 246 246 Copper 2.
FT DISULFID 141 227
FT CROSSLNK 76 76 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 189 189 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 216 216 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 241 241 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VARIANT 163 163 R -> W (found in a patient with
FT congenital cataracts, hearing loss,
FT neurodegeneration, neonatal hypotonia and
FT hypoglycemia, pericardial effusion and
FT neurodevelopmental regression after
FT infection; the patient also carries a
FT mutation in SLC33A1; mutant protein does
FT not interact with SOD1;
FT dbSNP:rs142340643).
FT /FTId=VAR_068078.
FT MUTAGEN 22 22 C->S: Reduces copper binding by half;
FT when associated with S-25. Negligible
FT effect on zinc binding.
FT MUTAGEN 25 25 C->S: Reduces copper binding by half;
FT when associated with S-22. Negligible
FT effect on zinc binding.
FT MUTAGEN 244 244 C->S: Reduces copper binding by half;
FT when associated with S-246. Negligible
FT effect on zinc binding.
FT MUTAGEN 246 246 C->S: Reduces copper binding by half;
FT when associated with S-244. Negligible
FT effect on zinc binding.
FT STRAND 12 18
FT HELIX 23 31
FT TURN 32 35
FT STRAND 41 45
FT TURN 46 49
FT STRAND 50 57
FT HELIX 59 67
FT TURN 68 70
FT STRAND 73 78
FT STRAND 87 94
FT STRAND 96 98
FT STRAND 100 109
FT STRAND 112 121
FT STRAND 124 133
FT HELIX 140 142
FT STRAND 161 163
FT STRAND 167 173
FT STRAND 177 187
FT HELIX 190 193
FT STRAND 196 203
FT TURN 213 220
FT STRAND 224 229
FT STRAND 231 233
SQ SEQUENCE 274 AA; 29041 MW; A392432954B65760 CRC64;
MASDSGNQGT LCTLEFAVQM TCQSCVDAVR KSLQGVAGVQ DVEVHLEDQM VLVHTTLPSQ
EVQALLEGTG RQAVLKGMGS GQLQNLGAAV AILGGPGTVQ GVVRFLQLTP ERCLIEGTID
GLEPGLHGLH VHQYGDLTNN CNSCGNHFNP DGASHGGPQD SDRHRGDLGN VRADADGRAI
FRMEDEQLKV WDVIGRSLII DEGEDDLGRG GHPLSKITGN SGERLACGII ARSAGLFQNP
KQICSCDGLT IWEERGRPIA GKGRKESAQP PAHL
//

MIM 603864
*RECORD*
*FIELD* NO
603864
*FIELD* TI
*603864 COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE; CCS
*FIELD* TX

CLONING

Copper (Cu) is required for aerobic life and yet, paradoxically, is
read morehighly toxic. This apparent contradiction has been rationalized by
assuming that Cu, like other redox-active metals, is sequestered in
nonreactive forms as it is transported into cells and moves through
cellular compartments. Culotta et al. (1997) determined that one such Cu
chaperone protein, Lys7, specifically delivers Cu to copper/zinc
superoxide dismutase (Sod1; 147450) in S. cerevisiae. By searching EST
databases, they identified cDNAs encoding the human Lys7 homolog, which
they named CCS (copper chaperone for SOD1). The predicted 274-amino acid
human protein is 28% identical to Lys7. CCS complemented a yeast Lys7
mutation, demonstrating that CCS is a functional homolog of Lys7.
Northern blot analysis revealed that CCS was expressed as a 1.2-kb mRNA
in all tissues and cell lines tested.

MAPPING

Bartnikas et al. (2000) mapped the CCS gene to chromosome 11q13 by
fluorescence in situ hybridization. They mapped the mouse Ccs gene to
the proximal or centromeric end of chromosome 9 by haplotype analysis of
a backcross panel.

GENE FUNCTION

Casareno et al. (1998) found that the region of CCS encompassing amino
acids 86-234 shares 47% identity with human SOD1. The residues of SOD1
identical to those of CCS include all of the known Cu and zinc ligands,
the dimerization interface, and most of the amino acid residues mutated
in familial ALS (105400). Binding assays and coimmunoprecipitation
studies indicated that SOD1 and CCS directly interact in vitro and in
vivo via the homologous domains in each protein. Immunofluorescence
analysis experiments showed that CCS and SOD1 were distributed in an
identical pattern throughout the cytoplasm and nucleus of mammalian
cells. The authors proposed that Cu delivery to SOD1 is mediated via a
direct interaction with CCS.

Rae et al. (1999) demonstrated that the yeast Lys7 gene product, yCCS,
activates Sod1 through direct insertion of the Cu cofactor. They found
that the concentration of intracellular free Cu is limited to less than
one free Cu ion per cell, suggesting that a pool of free Cu ions is not
used in physiologic activation of metalloenzymes. Instead, Cu-dependent
enzymes require accessory factors, such as the metallochaperone CCS, to
compete with chelators and processes that sequester essentially all
intracellular free Cu.

Casareno et al. (1998) demonstrated that CCS interacts not only with
wildtype SOD1 but also with SOD1 containing the common missense mutation
resulting in familial amyotrophic lateral sclerosis (FALS), A4V
(147450.0012), which is responsible for almost 50% of SOD1 mutations in
FALS cases. The findings revealed a common mechanism whereby different
SOD1 FALS mutants may result in neuronal injury and suggested a novel
therapeutic approach in patients affected by this fatal disease. The
delivery of copper by CCS to a target protein either unable or less able
to incorporate this metal would inevitably lead to copper-mediated
toxicity. Such a model is consistent with the failure to observe FALS in
transgenic mice lacking SOD1, because under such circumstances no
CCS-SOD1 interaction, and thus no copper transfer, will occur.

MOLECULAR GENETICS

Huppke et al. (2012) identified mutations in the SLC33A1 gene (603690)
in patients with an autosomal recessive disorder of congenital
cataracts, hearing loss, and neurodegeneration (CCHLND; 614482). One of
the patients, who had a nonsense mutation (603690.0004), was a Turkish
boy who had additional features not found in the other patients,
including neonatal hypotonia, hypoglycemia, and a pericardial effusion.
In this patient, Huppke et al. (2012) later identified a homozygous
missense mutation in the CCS gene (603864.0001) and suggested that a
defect in copper homeostasis or SOD1 deficiency may have contributed to
the phenotype.

ANIMAL MODEL

Wong et al. (2000) generated mice deficient in Ccs by targeted
disruption. Although the Ccs -/- mice were viable and possessed normal
levels of Sod1 protein, they revealed marked reductions in Sod1 activity
when compared with control littermates. Metabolic labeling with
copper-64 demonstrated that the reduction of Sod1 activity in Ccs -/-
mice was the direct result of impaired copper incorporation into Sod1
and that this effect was specific because no abnormalities were observed
in copper uptake, distribution, or incorporation into other copper
enzymes. Consistent with this loss of Sod1 activity, Ccs -/- mice showed
increased sensitivity to paraquat and reduced female fertility,
phenotypes that are characteristic of Sod1-deficient mice. Wong et al.
(2000) concluded that their results demonstrate the essential role of
any mammalian copper chaperone.

Subramaniam et al. (2002) bred Ccs heterozygotes to Sod1 heterozygotes
generate double-knockout mice. Motor neurons in Ccs -/- mice showed
increased rate of death after facial nerve axotomy, a response
documented for Sod1 -/- mice. Thus, CCS is necessary for the efficient
incorporation of copper into SOD1 in motor neurons. Although the absence
of Ccs led to a significant reduction in the amount of copper-loaded
mutant Sod1, it did not modify the onset and progression of motor neuron
disease in Sod1-mutant mice. Subramaniam et al. (2002) concluded that
CCS-dependent copper loading of mutant SOD1 plays no role in the
pathogenesis of motor neuron disease in these mouse models.

*FIELD* AV
.0001
VARIANT OF UNKNOWN SIGNIFICANCE
CCS, ARG163TRP

This variant is classified as a variant of unknown significance because
its contribution to an early-onset neurodegenerative disorder has not
been confirmed.

In a Turkish boy, born of consanguineous parents, with an early-onset
neurodegenerative disorder resulting in death at age 3.5 years, Huppke
et al. (2012) identified a homozygous 487C-T transition in exon 5 of the
CCS gene, resulting in an arg163-to-trp (R163W) substitution at a highly
conserved residue in domain II. The patient had previously been reported
by Huppke et al. (2012) as having congenital cataracts, hearing loss,
and neurodegeneration (CCHLND; 614482) due to a homozygous truncating
mutation in the SLC33A1 gene (Y366X; 603690.0004). Complementation
studies in yeast lacking Ccs indicated that the mutant CCS protein
showed about 50% complementation compared to wildtype, and studies in
HeLa cells showed that the mutant CCS protein had decreased binding with
SOD1 (147450). Studies in patient fibroblasts showed that CCS protein
levels were about 40% of controls and that SOD1 (147450) enzyme activity
was significantly decreased. Patient fibroblasts also showed evidence of
the unfolded protein response, which may reflect cellular oxidative
stress. The patient with the CCS variant had additional symptoms not
present in the other patients with SLC33A1 mutations, including neonatal
hypotonia, hypoglycemia, and a pericardial effusion. At age 18 months,
he had rapid developmental regression and epilepsy with persistent
bilateral thalamic lesions on brain MRI. Huppke et al. (2012) suggested
that a defect in copper homeostasis or SOD1 deficiency may have
contributed to the phenotype in this patient. Direct DNA sequencing
excluded mutations in the CCS gene in 35 patients with developmental
delay and low serum copper and ceruloplasmin who did not have mutations
in the ATP7A (300011) or ATP7B (606882) genes.

*FIELD* RF
1. Bartnikas, T. B.; Waggoner, D. J.; Casareno, R. L. B.; Gaedigk,
R.; White, R. A.; Gitlin, J. D.: Chromosomal localization of CCS,
the copper chaperone for Cu/Zn superoxide dismutase. Mammalian Genome 11:
409-411, 2000.

2. Casareno, R. L. B.; Waggoner, D.; Gitlin, J. D.: The copper chaperone
CCS directly interacts with copper/zinc superoxide dismutase. J.
Biol. Chem. 273: 23625-23628, 1998.

3. Culotta, V. C.; Klomp, L. W. J.; Strain, J.; Casareno, R. L. B.;
Krems, B.; Gitlin, J. D.: The copper chaperone for superoxide dismutase. J.
Biol. Chem. 272: 23469-23472, 1997.

4. Huppke, P.; Brendel, C.; Kalscheuer, V.; Korenke, G. C.; Marquardt,
I.; Freisinger, P.; Christodoulou, J.; Hillebrand, M.; Pitelet, G.;
Wilson, C.; Gruber-Sedlmayr, U.; Ullmann, R.; Haas, S.; Elpeleg, O.;
Nurnberg, G.; Nurnberg, P.; Dad, S.; Moller, L. B.; Kaler, S. G.;
Gartner, J.: Mutations in SLC33A1 cause a lethal autosomal-recessive
disorder with congenital cataracts, hearing loss, and low serum copper
and ceruloplasmin. Am. J. Hum. Genet. 90: 61-68, 2012. Note: Erratum:
Am. J. Hum. Genet. 90: 378 only, 2012.

5. Huppke, P.; Brendel, C.; Korenke, G. C.; Marquardt, I.; Donsante,
A.; Yi, L.; Hicks, J. D.; Steinbach, P. J.; Wilson, C.; Elpeleg, O.;
Moller, L. B.; Christodoulou, J.; Kaler, S. G.; Gartner, J.: Molecular
and biochemical characterization of a unique mutation in CCS, the
human copper chaperone to superoxide dismutase. Hum. Mutat. 33:
1207-1215, 2012.

6. Rae, T. D.; Schmidt, P. J.; Pufahl, R. A.; Culotta, V. C.; O'Halloran,
T. V.: Undetectable intracellular free copper: the requirement of
a copper chaperone for superoxide dismutase. Science 284: 805-808,
1999.

7. Subramaniam, J. R.; Lyons, W. E.; Liu, J.; Bartnikas, T. B.; Rothstein,
J.; Price, D. L.; Cleveland, D. W.; Gitlin, J. D.; Wong, P. C.: Mutant
SOD1 causes motor neuron disease independent of copper chaperone-mediated
copper loading. Nature Neurosci. 5: 301-307, 2002.

8. Wong, P. C.; Waggoner, D.; Subramaniam, J. R.; Tessarollo, L.;
Bartnikas, T. B.; Culotta, V. C.; Price, D. L.; Rothstein, J.; Gitlin,
J. D.: Copper chaperone for superoxide dismutase is essential to
activate mammalian Cu/Zn superoxide dismutase. Proc. Nat. Acad. Sci. 97:
2886-2891, 2000.

*FIELD* CN
Cassandra L. Kniffin - updated: 9/4/2012
Ada Hamosh - updated: 3/28/2002
Victor A. McKusick - updated: 5/18/2000
Victor A. McKusick - updated: 9/20/1999

*FIELD* CD
Rebekah S. Rasooly: 6/2/1999

*FIELD* ED
carol: 07/26/2013
carol: 9/5/2012
ckniffin: 9/4/2012
carol: 12/13/2011
alopez: 4/12/2002
mgross: 3/29/2002
terry: 3/28/2002
carol: 5/25/2000
terry: 5/18/2000
jlewis: 9/29/1999
terry: 9/20/1999
carol: 7/26/1999
alopez: 6/2/1999