UniProtKB/Swiss-Prot P35670: Variant p.Gly875Arg

Copper-transporting ATPase 2
Gene: ATP7B
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Variant information Variant position:

875 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Glycine (G) to Arginine (R) at position 875 (G875R, p.Gly875Arg). 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 glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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:

Individuals heterozygous for Wilson disease mutations on the R-875 background may manifest the disease phenotype under conditions of copper deficiency; affects protein folding; localized to the ER and absent from TGN under low copper conditions; in response to high copper levels it relocalizes to vesicles and properly cycle back to TGN. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs587783304 [ dbSNP | Ensembl ]

Sequence information Variant position:

875 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1465 The length of the canonical sequence.
Location on the sequence:

SLITGEAMPVTKKPGSTVIA G SINAHGSVLIKATHVGNDTT 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                         SLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTT

Mouse                         SLITGEAMPVTKKPGSIVIAGSINAHGSVLLKATHVGNDTT

Rat                           SLITGEAMPVTKKPGSIVIAGSINAHGSVLIKATHVGNDTT

Sheep                         SLITGEAMPVTKKPGSMVIAGSMNAHGSVLITATHVGNDTT

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.

Type	Positions	Description
Chain	1 – 1465	Copper-transporting ATPase 2
Topological domain	786 – 919	Cytoplasmic
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.

Literature citations
Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions.
Petrukhin K.; Lutsenko S.; Chernov I.; Ross B.M.; Kaplan J.H.; Gilliam T.C.;
Hum. Mol. Genet. 3:1647-1656(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS ASP-96; ARG-875 AND LYS-952; The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.
Tanzi R.E.; Petrukhin K.; Chernov I.; Pellequer J.L.; Wasco W.; Ross B.; Romano D.M.; Parano E.; Pavone L.; Brzustowicz L.M.; Devoto M.; Peppercorn J.; Bush A.I.; Sternlieb I.; Pirastu M.; Gusella J.F.; Evgrafov O.; Penchaszadeh G.K.; Honig B.; Edelman I.S.; Soares M.B.; Scheinberg I.H.; Gilliam T.C.;
Nat. Genet. 5:344-350(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 149-1465 (ISOFORM 2); VARIANTS WD GLN-1069 AND SER-1270; VARIANT ARG-875; Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease.
Wu Z.Y.; Wang N.; Lin M.T.; Fang L.; Murong S.X.; Yu L.;
Arch. Neurol. 58:971-976(2001)
Cited for: VARIANTS VAL-390; ALA-406; LEU-456; GLY-723; ARG-832; ARG-875; VAL-929; LYS-952 AND ALA-1140; VARIANTS WD VAL-769; GLN-778; LEU-778; VAL-874; GLY-919; MET-935; ASP-943; PRO-1041; ILE-1106; HIS-1142; LYS-1173 AND SER-1270; Cellular copper levels determine the phenotype of the Arg875 variant of ATP7B/Wilson disease protein.
Gupta A.; Bhattacharjee A.; Dmitriev O.Y.; Nokhrin S.; Braiterman L.; Hubbard A.L.; Lutsenko S.;
Proc. Natl. Acad. Sci. U.S.A. 108:5390-5395(2011)
Cited for: CHARACTERIZATION OF VARIANT ARG-875;

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.