UniProtKB/Swiss-Prot P35670 : Variant p.Gly626Ala
Copper-transporting ATPase 2
Gene: ATP7B
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Variant information
Variant position:
626
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
US
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 Alanine (A) at position 626 (G626A, p.Gly626Ala).
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 small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
0
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; uncertain significance; no effect on protein abundance; no effect on protein localization; may have an effect on copper transport activity; no effect on ATPase activity; does not affect interaction with COMMD1.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
626
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:
VKFDPEIIGPRDIIKIIEEI
G FHASLAQRNPNAHHLDHKME
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 VKFDPEIIGPRDIIKIIEEIG FHASLAQRNPNAHHLDHKME
Mouse VKFDPEIVGPRDIIKIIEEIG FHASLAQRNPNAHHLDHKTE
Rat VKFDPEIIGPRDIIKVIEEIG FHASLAHRNPNAHHLDHKTE
Sheep VKFDPEIIGPRDIVKLIEEIG FRASLAQRIPNAHHLDHKVE
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
1 – 653
Cytoplasmic
Domain
564 – 630
HMA 6
Alternative sequence
234 – 1465
RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.
Alternative sequence
624 – 785
Missing. In isoform 2.
Literature citations
Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B.
de Bie P.; van de Sluis B.; Burstein E.; van de Berghe P.V.; Muller P.; Berger R.; Gitlin J.D.; Wijmenga C.; Klomp L.W.;
Gastroenterology 133:1316-1326(2007)
Cited for: SUBCELLULAR LOCATION; INTERACTION WITH COMMD1 AND ATOX1; CHARACTERIZATION OF VARIANTS WD SER-41; VAL-85; SER-486; SER-492; HIS-532; LYS-541; ASP-591; PRO-604; GLN-616; TRP-616; ALA-626; SER-641; HIS-642 AND ARG-645;
Diverse functional properties of Wilson disease ATP7B variants.
Huster D.; Kuehne A.; Bhattacharjee A.; Raines L.; Jantsch V.; Noe J.; Schirrmeister W.; Sommerer I.; Sabri O.; Berr F.; Moessner J.; Stieger B.; Caca K.; Lutsenko S.;
Gastroenterology 142:947-956(2012)
Cited for: CHARACTERIZATION OF VARIANTS WD VAL-85; SER-492; TRP-616; ALA-626; ARG-645; SER-710; LEU-760; ASN-765; VAL-769; LEU-840; THR-857; VAL-874; GLN-969; LEU-992; LEU-1052; LYS-1064; GLN-1069; PHE-1083; VAL-1213; VAL-1222; ARG-1266; SER-1270 AND LEU-1273; CHARACTERIZATION OF VARIANTS ALA-406; LEU-456 AND ARG-832; MUTAGENESIS OF ASP-1027 AND THR-1031; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION;
Distinct phenotype of a Wilson disease mutation reveals a novel trafficking determinant in the copper transporter ATP7B.
Braiterman L.T.; Murthy A.; Jayakanthan S.; Nyasae L.; Tzeng E.; Gromadzka G.; Woolf T.B.; Lutsenko S.; Hubbard A.L.;
Proc. Natl. Acad. Sci. U.S.A. 111:E1364-E1373(2014)
Cited for: CHARACTERIZATION OF VARIANTS WD ALA-626; TYR-639; SER-641; HIS-642; ARG-645 AND TYR-653; MUTAGENESIS OF SER-653; FUNCTION; SUBCELLULAR LOCATION;
Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.
Figus A.; Angius A.; Loudianos G.; Bertini C.; Dessi V.; Loi A.; Deiana M.; Lovicu M.; Olla N.; Sole G.; de Virgiliis S.; Lilliu F.; Farci A.M.G.; Nurchi A.; Giacchino R.; Barabino A.; Marazzi M.; Zancan L.; Greggio N.A.; Macellini M.; Solinas A.; Deplano A.; Barbera C.; Devoto M.; Ozsoylu S.; Kocak N.; Akar N.; Karayalcin S.; Mokini V.; Cullufi P.; Balestrieri A.; Cao A.; Pirastu M.;
Am. J. Hum. Genet. 57:1318-1324(1995)
Cited for: VARIANTS WD ALA-626; ASN-765; GLY-778; THR-857; GLN-969; LYS-1064 AND SER-1270;
Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses.
Shah A.B.; Chernov I.; Zhang H.T.; Ross B.M.; Das K.; Lutsenko S.; Parano E.; Pavone L.; Evgrafov O.; Ivanova-Smolenskaya I.A.; Anneren G.; Westermark K.; Urrutia F.H.; Penchaszadeh G.K.; Sternlieb I.; Scheinberg I.H.; Gilliam T.C.; Petrukhin K.;
Am. J. Hum. Genet. 61:317-328(1997)
Cited for: VARIANTS WD ALA-626; ARG-645; PRO-708; SER-710; TRP-778; PHE-795; ARG-869; VAL-1035; ALA-1064; GLN-1069; CYS-1186; TYR-1222; VAL-1266; SER-1270; PRO-1322 AND ARG-1353;
Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population.
Todorov T.; Savov A.; Jelev H.; Panteleeva E.; Konstantinova D.; Krustev Z.; Mihaylova V.; Tournev I.; Tankova L.; Tzolova N.; Kremensky I.;
Clin. Genet. 68:474-476(2005)
Cited for: VARIANTS WD GLN-616; ALA-626; TRP-778; GLY-778; VAL-874; GLN-969; THR-1003; GLN-1069; 1217-VAL-LEU-1218 DEL; SER-1270; TYR-1279; ASP-1341; SER-1352 AND PRO-1368;
Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system.
Hsi G.; Cullen L.M.; Macintyre G.; Chen M.M.; Glerum D.M.; Cox D.W.;
Hum. Mutat. 29:491-501(2008)
Cited for: CHARACTERIZATION OF VARIANTS WD HIS-532; ALA-626; HIS-642; TRP-1041; LYS-1064; PHE-1083; ASP-1106; VAL-1169; THR-1183 AND SER-1186; CHARACTERIZATION OF VARIANT ALA-1140; FUNCTION;
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.