UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1064

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 Glutamate (E) to Alanine (A) at position 1064 (E1064A, p.Glu1064Ala).

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 acidic (E) to small size and hydrophobic (A)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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 WD; does not bind ATP; the mutant is stable and is properly targeted to the TGN.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs374094065 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1064

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:

LLGDVATLPLRKVLAVVGTA E ASSEHPLGVAVTKYCKEELG

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                         LLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELG

Mouse                         LLADVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELG

Rat                           LLVDVATLSLRKVLAVVGTAEASSEHPLGVAVTKYCKEELG

Sheep                         LLVDLATLPLRKVLAVVGTAEASSEHPLGVAVTRYCKEELG

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	995 – 1322	Cytoplasmic
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.
Mutagenesis	1069 – 1069	H -> AC. Loss of ATPase activity. Cannot form an acylphosphate intermediate during catalysis. Does not alter folding of the nucleotide-binding domain.
Helix	1053 – 1064

Literature citations

Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A and H1069Q mutants of copper-transporting ATPase ATP7B.
Dmitriev O.Y.; Bhattacharjee A.; Nokhrin S.; Uhlemann E.M.; Lutsenko S.;
J. Biol. Chem. 286:16355-16362(2011)
Cited for: CHARACTERIZATION OF VARIANTS WD ALA-1064 AND GLN-1069;

Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups.
Kalinsky H.; Funes A.; Zeldin A.; Pel-Or Y.; Korostishevsky M.; Gershoni-Baruch R.; Farrer L.A.; Bonne-Tamir B.;
Hum. Mutat. 11:145-151(1998)
Cited for: VARIANTS WD ARG-645; ASN-765; GLN-969; ALA-1064; GLN-1069; VAL-1213 AND 1216-VAL-VAL-1217 DEL; VARIANTS SER-565; GLY-723; ARG-832 AND ALA-1140;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35670: Variant p.Glu1064Ala