UniProtKB/Swiss-Prot P78363 : Variant p.Thr959Ile
Retinal-specific phospholipid-transporting ATPase ABCA4
Gene: ABCA4
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Variant information
Variant position:
959
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Threonine (T) to Isoleucine (I) at position 959 (T959I, p.Thr959Ile).
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 (T) to medium size and hydrophobic (I)
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 STGD1; likely pathogenic; highly decreased ATPase activity; highly decreased phospholipid translocase activity.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
959
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
2273
The length of the canonical sequence.
Location on the sequence:
EPCGRPAVDRLNITFYENQI
T AFLGHNGAGKTTTLSILTGL
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 EP--CGRPAVDRLNITFYENQIT AFLGHNGAGKTTTLSILTGL
Mouse EP--SGRPAVDRLNITFYENQIT AFLGHNGAGKTTTLSILT
Bovine EP--YGRPAVDRLNITFYESQIT AFLGHNGAGKTTTLSIMT
Slime mold KTGDGNRIAVNDLSIDMYKNRIH SFLGPNGSGKSTTLSMLT
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 – 2273
Retinal-specific phospholipid-transporting ATPase ABCA4
Topological domain
857 – 1376
Cytoplasmic
Domain
929 – 1160
ABC transporter 1
Binding site
966 – 966
Binding site
969 – 969
Binding site
970 – 970
Binding site
971 – 971
Disulfide bond
641 – 1490
Interchain
Mutagenesis
940 – 940
P -> R. Decreases 11-cis-Retinal binding affinity by 50%.
Mutagenesis
965 – 965
N -> A. No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity.
Mutagenesis
965 – 965
N -> DK. Decreased N-Ret-PE binding to 50%-63% of wild-type values.
Mutagenesis
965 – 965
N -> DK. Results in minimal, if any, basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity.
Mutagenesis
965 – 965
N -> Q. Decreased basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity.
Mutagenesis
966 – 966
G -> D. Abolishes basal and retinal-stimulated ATP hydrolysis.
Mutagenesis
969 – 969
K -> M. Abolishes basal and retinal-stimulated ATP hydrolysis.
Mutagenesis
969 – 969
K -> M. Inhibits ATPase activity; when associated with M-1978. Decreases translocase activity; when associated with M-1978. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-1978. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect N-retinylidene-PE binding. Impairs ATP-dependent release of N-retinylidene-PE. Significantly reduces PE flippase activity.
Beta strand
956 – 960
Literature citations
Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
Quazi F.; Molday R.S.;
J. Biol. Chem. 288:34414-34426(2013)
Cited for: CATALYTIC ACTIVITY; ACTIVITY REGULATION; FUNCTION; SUBCELLULAR LOCATION; VARIANTS STGD1 PRO-100; LEU-608; ILE-959; SER-965 AND MET-1537; CHARACTERIZATION OF VARIANTS STGD1 PRO-100; LEU-608; ILE-959; SER-965 AND MET-1537; MUTAGENESIS OF CYS-1502; ARG-2107 AND PRO-2180;
A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.
Rivera A.; White K.; Stoehr H.; Steiner K.; Hemmrich N.; Grimm T.; Jurklies B.; Lorenz B.; Scholl H.P.N.; Apfelstedt-Sylla E.; Weber B.H.F.;
Am. J. Hum. Genet. 67:800-813(2000)
Cited for: VARIANTS STGD1 GLU-60; THR-60; GLU-65; LEU-68; ARG-72; CYS-212; SER-230; SER-247; VAL-328; LYS-471; PRO-541; GLN-572; ARG-607; LYS-635; CYS-653; TYR-764; ARG-765; ALA-901; ILE-959; LYS-1036; VAL-1038; PRO-1063; ASP-1087; CYS-1097; CYS-1108; LEU-1380; LYS-1399; PRO-1430; VAL-1440; HIS-1443; LEU-1486; TYR-1488; MET-1537; PRO-1689; LEU-1705; THR-1733; ARG-1748; PRO-1763; LYS-1885; HIS-1898; GLU-1961; ARG-1975; SER-1977; GLY-2077; TRP-2077 AND VAL-2241; VARIANTS GLN-152; HIS-212; ARG-423; ILE-552; ARG-914; GLN-943; THR-1562; ILE-1868; MET-1921; LEU-1948; PHE-1970; ALA-2059; ASN-2177 AND VAL-2216;
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.