O14618 (CCS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Copper chaperone for superoxide dismutase

Alternative name(s):
Superoxide dismutase copper chaperone

Gene names

Name:

CCS

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	274 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Delivers copper to copper zinc superoxide dismutase (SOD1).
Cofactor	Binds 2 copper ions per subunit. Binds 1 zinc ion per subunit.
Subunit structure	Homodimer, and heterodimer with SOD1. Interacts with COMMD1. Ref.4 Ref.7 Ref.9
Subcellular location	Cytoplasm Ref.4.
Tissue specificity	Ubiquitous.
Sequence similarities	In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family. Contains 1 HMA domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Copper Metal-binding Zinc
Molecular function	Chaperone
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular copper ion transport Inferred from Biological aspect of Ancestor. Source: RefGenome removal of superoxide radicals Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrial inner membrane Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from direct assay Ref.4. Source: UniProtKB soluble fraction Traceable author statement. Source: ProtInc
Molecular function	copper ion transmembrane transporter activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction Ref.4. Source: UniProtKB superoxide dismutase activity Inferred from electronic annotation. Source: InterPro superoxide dismutase copper chaperone 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

Chain

1 – 274

274

Copper chaperone for superoxide dismutase

PRO_0000213543

Regions

Domain

12 – 75

64

HMA

Region

88 – 234

147

Superoxide dismutase-like

Sites

Metal binding

22

1

Copper 1

Metal binding

25

1

Copper 1

Metal binding

147

1

Zinc

Metal binding

155

1

Zinc

Metal binding

164

1

Zinc

Metal binding

167

1

Zinc

Metal binding

244

1

Copper 2

Metal binding

246

1

Copper 2

Amino acid modifications

Modified residue

267

1

Phosphoserine Ref.6

Disulfide bond

141 ↔ 227

Ref.9

Experimental info

Mutagenesis

22

1

C → S: Reduces copper binding by half; when associated with S-25. Negligible effect on zinc binding. Ref.5

Mutagenesis

25

1

C → S: Reduces copper binding by half; when associated with S-22. Negligible effect on zinc binding. Ref.5

Mutagenesis

244

1

C → S: Reduces copper binding by half; when associated with S-246. Negligible effect on zinc binding. Ref.5

Mutagenesis

246

1

C → S: Reduces copper binding by half; when associated with S-244. Negligible effect on zinc binding. Ref.5

Secondary structure

1

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274

Helix Strand Turn

Details...

Beta strand

12 – 18

7

Helix

23 – 31

9

Turn

32 – 35

4

Beta strand

41 – 45

5

Turn

46 – 49

4

Beta strand

50 – 57

8

Helix

59 – 67

9

Turn

68 – 70

3

Beta strand

73 – 78

6

Beta strand

87 – 94

8

Beta strand

96 – 98

3

Beta strand

100 – 109

10

Beta strand

112 – 121

10

Beta strand

124 – 133

10

Helix

140 – 142

3

Beta strand

161 – 163

3

Beta strand

167 – 173

7

Beta strand

177 – 187

11

Helix

190 – 193

4

Beta strand

196 – 203

8

Turn

213 – 220

8

Beta strand

224 – 229

6

Beta strand

231 – 233

3

Sequences

	Sequence		Length	Mass (Da)
	O14618 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: A392432954B65760	FASTA	274	29,041
	10 20 30 40 50 60 MASDSGNQGT LCTLEFAVQM TCQSCVDAVR KSLQGVAGVQ DVEVHLEDQM VLVHTTLPSQ 70 80 90 100 110 120 EVQALLEGTG RQAVLKGMGS GQLQNLGAAV AILGGPGTVQ GVVRFLQLTP ERCLIEGTID 130 140 150 160 170 180 GLEPGLHGLH VHQYGDLTNN CNSCGNHFNP DGASHGGPQD SDRHRGDLGN VRADADGRAI 190 200 210 220 230 240 FRMEDEQLKV WDVIGRSLII DEGEDDLGRG GHPLSKITGN SGERLACGII ARSAGLFQNP 250 260 270 KQICSCDGLT IWEERGRPIA GKGRKESAQP PAHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The copper chaperone for superoxide dismutase." Culotta V.C., Klomp L.W., Strain J., Casareno R.L.B., Krems B., Gitlin J.D. J. Biol. Chem. 272:23469-23472(1997) [PubMed: 9295278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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].
[3]	"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]. Tissue: Brain.
[4]	"The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase." Casareno R.L.B., Waggoner D., Gitlin J.D. J. Biol. Chem. 273:23625-23628(1998) [PubMed: 9726962] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[5]	"Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface." Stasser J.P., Eisses J.F., Barry A.N., Kaplan J.H., Blackburn N.J. Biochemistry 44:3143-3152(2005) [PubMed: 15736924] [Abstract] Cited for: MUTAGENESIS OF CYS-22; CYS-25; CYS-244 AND CYS-246, METAL-BINDING.
[6]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-267, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1." Vonk W.I., Wijmenga C., Berger R., van de Sluis B., Klomp L.W. J. Biol. Chem. 285:28991-29000(2010) [PubMed: 20595380] [Abstract] Cited for: INTERACTION WITH COMMD1.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystal structure of the second domain of the human copper chaperone for superoxide dismutase." Lamb A.L., Wernimont A.K., Pufahl R.A., O'Halloran T.V., Rosenzweig A.C. Biochemistry 39:1589-1595(2000) [PubMed: 10677207] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 84-237 IN COMPLEX WITH ZINC, SUBUNIT, DISULFIDE BOND.
[10]	"The apo form of HMA domain of copper chaperone for superoxide dismutase." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-87.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF002210 mRNA. Translation: AAC51764.1.
CR541928 mRNA. Translation: CAG46726.1.
BC105016 mRNA. Translation: AAI05017.1.
BC112055 mRNA. Translation: AAI12056.1.

IPI

IPI00021389.

RefSeq

NP_005116.1. NM_005125.1.

UniGene

Hs.502917.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DO5	X-ray	2.75	A/B/C/D	84-237	[»]
2CRL	NMR	-	A	1-85	[»]

ProteinModelPortal

O14618.

SMR

O14618. Positions 7-237.

ModBase

Search...

Protein-protein interaction databases

STRING

O14618.

PTM databases

PhosphoSite

O14618.

2D gel databases

OGP

O14618.

Proteomic databases

PRIDE

O14618.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310190; ENSP00000307870; ENSG00000173992.

GeneID

9973.

KEGG

hsa:9973.

UCSC

uc001oir.1. human.

Organism-specific databases

CTD

9973.

GeneCards

GC11P066360.

H-InvDB

HIX0035845.

HGNC

HGNC:1613. CCS.

HPA

CAB008672.

MIM

603864. gene.

neXtProt

NX_O14618.

PharmGKB

PA26177.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17226.

HOGENOM

HBG324056.

HOVERGEN

HBG018933.

InParanoid

O14618.

OMA

CDGVTLW.

OrthoDB

EOG45TCNZ.

PhylomeDB

O14618.

Gene expression databases

ArrayExpress

O14618.

Bgee

O14618.

CleanEx

HS_CCS.

Genevestigator

O14618.

GermOnline

ENSG00000173992. Homo sapiens.

Family and domain databases

InterPro

IPR006121. HeavyMe-assoc_HMA.
IPR024134. SOD_Cu/Zn_/chaperones.
IPR018152. SOD_Cu/Zn_BS.
IPR024142. SOD_Cu_chaperone.
IPR001424. SOD_Cu_Zn_dom.
[Graphical view]

Gene3D

G3DSA:2.60.40.200. SOD_Cu_Zn. 1 hit.

KO

K04569.

PANTHER

PTHR10003:SF27. PTHR10003:SF27. 1 hit.
PTHR10003. SOD_Cu_Zn. 1 hit.

Pfam

PF00403. HMA. 1 hit.
PF00080. Sod_Cu. 1 hit.
[Graphical view]

PRINTS

PR00068. CUZNDISMTASE.

SUPFAM

SSF55008. HeavyMe_transpt. 1 hit.
SSF49329. SOD_Cu_Zn. 1 hit.

PROSITE

PS01047. HMA_1. False negative.
PS50846. HMA_2. 1 hit.
PS00087. SOD_CU_ZN_1. False negative.
PS00332. SOD_CU_ZN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

37666.

SOURCE

Search...

Entry information

Entry name

CCS_HUMAN

Accession

Primary (citable) accession number: O14618
Secondary accession number(s): Q2M366

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 112 of the entry and version 1 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.