UniProtKB/SwissProt variant VAR

Variant information

Variant position:

201

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 Glycine (G) to Cysteine (C) at position 201 (G201C, p.Gly201Cys).

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 medium size and polar (C)

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 LESKRES; impairs shRNA-mediated silencing. Does not affect targeting to P-bodies. Increases binding to mRNA targets. Does not affect interaction with DICER1. Decreased phosphorylation of the C-terminal serine cluster. Does not affect phosphorylation of Ser-387.

Any additional useful information about the variant.

Sequence information

Variant position:

201

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

Protein sequence length:

859

The length of the canonical sequence.

Location on the sequence:

FFTASEGCSNPLGGGREVWF G FHQSVRPSLWKMMLNIDVSA

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                         FFTASE-GCSNPLGGGREVWFGFHQSV----RPSLWKMMLNIDVSA

Mouse                         FFTASE-GCSNPLGGGREVWFGFHQSV----RPSLWKMMLN

Rat                           FFTASE-GCSNPLGGGREVWFGFHQSV----RPSLWKMMLN

Bovine                        FFTASE-GCSNPLGGGREVWFGFHQSV----RPSLWKMMLN

Xenopus laevis                FFTASE-GCANPLGGGREVWFGFHQSV----RPSLWKMMLN

Xenopus tropicalis            FFTASE-GCANPLGGGREVWFGFHQSV----RPSLWKMMLN

Drosophila                    FFKMSDPNNRHELDDGYEALVGLYQAFMLGDRP-----FLN

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 – 859	Protein argonaute-2
Beta strand	196 – 207

Literature citations

Germline AGO2 mutations impair RNA interference and human neurological development.
Lessel D.; Zeitler D.M.; Reijnders M.R.F.; Kazantsev A.; Hassani Nia F.; Bartholomaeus A.; Martens V.; Bruckmann A.; Graus V.; McConkie-Rosell A.; McDonald M.; Lozic B.; Tan E.S.; Gerkes E.; Johannsen J.; Denecke J.; Telegrafi A.; Zonneveld-Huijssoon E.; Lemmink H.H.; Cham B.W.M.; Kovacevic T.; Ramsdell L.; Foss K.; Le Duc D.; Mitter D.; Syrbe S.; Merkenschlager A.; Sinnema M.; Panis B.; Lazier J.; Osmond M.; Hartley T.; Mortreux J.; Busa T.; Missirian C.; Prasun P.; Luettgen S.; Mannucci I.; Lessel I.; Schob C.; Kindler S.; Pappas J.; Rabin R.; Willemsen M.; Gardeitchik T.; Loehner K.; Rump P.; Dias K.R.; Evans C.A.; Andrews P.I.; Roscioli T.; Brunner H.G.; Chijiwa C.; Lewis M.E.S.; Jamra R.A.; Dyment D.A.; Boycott K.M.; Stegmann A.P.A.; Kubisch C.; Tan E.C.; Mirzaa G.M.; McWalter K.; Kleefstra T.; Pfundt R.; Ignatova Z.; Meister G.; Kreienkamp H.J.;
Nat. Commun. 11:5797-5797(2020)
Cited for: INVOLVEMENT IN LESKRES; VARIANTS LESKRES CYS-201; VAL-201; GLN-203; MET-357; THR-364; PRO-367; SER-573; ARG-733; TYR-751 AND ARG-760; CHARACTERIZATION OF VARIANTS LESKRES PRO-192; CYS-201; VAL-201; GLN-203; MET-357; THR-364; PRO-367; SER-573; ARG-733; TYR-751 AND ARG-760; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-387; INTERACTION WITH DICER1;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UKV8: Variant p.Gly201Cys