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UniProtKB/Swiss-Prot Q04656: Variant p.Cys1000Arg

Copper-transporting ATPase 1
Gene: ATP7A
Variant information

Variant position:  1000
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Cysteine (C) to Arginine (R) at position 1000 (C1000R, p.Cys1000Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In MNK; decreased protein abundance; increased protein degradation; does not affect interaction with ATOX1; does not affect interaction with COMMD1; subcellular location restricted to TGN; does not localizes to the plasma membrane in response to elevated copper levels; impaired copper transport activity.
Any additional useful information about the variant.



Sequence information

Variant position:  1000
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1500
The length of the canonical sequence.

Location on the sequence:   RTETIIRFAFQASITVLCIA  C PCSLGLATPTAVMVGTGVGA
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGA

Mouse                         RTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGA

Rat                           RTETIIRFAFQASITVLCIACPCSLGLATPTAVMVGTGVGA

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 1500 Copper-transporting ATPase 1
Transmembrane 990 – 1011 Helical
Alternative sequence 42 – 1038 Missing. In isoform 3.
Alternative sequence 82 – 1499 Missing. In isoform 6.


Literature citations

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression.
Vonk W.I.; de Bie P.; Wichers C.G.; van den Berghe P.V.; van der Plaats R.; Berger R.; Wijmenga C.; Klomp L.W.; van de Sluis B.;
Cell. Mol. Life Sci. 69:149-163(2012)
Cited for: INTERACTION WITH ATOX1 AND COMMD1; CHARACTERIZATION OF VARIANT OHS SER-1304; CHARACTERIZATION OF VARIANTS MNK ARG-873; ARG-1000 AND ASP-1362;

Identification and analysis of 21 novel disease-causing amino acid substitutions in the conserved part of ATP7A.
Moeller L.B.; Bukrinsky J.T.; Moelgaard A.; Paulsen M.; Lund C.; Tuemer Z.; Larsen S.; Horn N.;
Hum. Mutat. 26:84-93(2005)
Cited for: VARIANTS MNK HIS-844; ARG-853; VAL-860; ARG-876; GLU-876; ARG-924; ARG-1000; VAL-1007; ASP-1015; GLY-1044; PRO-1100; GLU-1282; GLU-1300; VAL-1302; LYS-1304; ALA-1305; ARG-1315; VAL-1325; ARG-1369 AND PHE-1397;

Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease.
Skjoerringe T.; Amstrup Pedersen P.; Salling Thorborg S.; Nissen P.; Gourdon P.; Birk Moeller L.;
Sci. Rep. 7:757-757(2017)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS MNK VAL-628; ARG-633; TYR-653; ARG-666; ARG-727; ASP-728; PRO-761; ASN-802; HIS-844; VAL-860; ARG-876; GLU-876; ARG-1000; ARG-1005; VAL-1007; ASP-1015; ASN-1037; GLY-1044; ARG-1255; GLU-1282; GLU-1300; GLY-1301; GLU-1302; VAL-1302; LYS-1304; ALA-1305; GLY-1305; ASP-1308; ARG-1315; VAL-1325; VAL-1362; ARG-1369; PRO-1373; THR-1393 AND PHE-1397; CHARACTERIZATION OF VARIANT OHS ARG-924;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.