UniProtKB/Swiss-Prot Q13283: Variant p.Val366Met

Ras GTPase-activating protein-binding protein 1
Gene: G3BP1
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Variant information Variant position:

366 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 Valine (V) to Methionine (M) at position 366 (V366M, p.Val366Met). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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:

Found in a patient with a neurodevelopmental disorder; uncertain significance; no effect on function in stress granule formation shown by rescue assays in transfected G3BP1-deficient cells. Any additional useful information about the variant.

Sequence information Variant position:

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

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

NLPHEVDKSELKDFFQSYGN V VELRINSGGKLPNFGFVVFD 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                         NLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFD

Mouse                         NLPHEVDKSELKDFFQNFGNVVELRINSGGKLPNFGFVVFD

Bovine                        NLPHEVDKSELKDFFQNYGNVVELRINSGGKLPNFGFVVFD

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	2 – 466	Ras GTPase-activating protein-binding protein 1
Domain	340 – 415	RRM
Modified residue	373 – 373	Phosphoserine
Modified residue	376 – 376	N6-acetyllysine; alternate
Cross	353 – 353	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	357 – 357	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	376 – 376	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Cross	376 – 376	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence	123 – 466	Missing. In isoform 2.
Mutagenesis	353 – 353	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123,R-357, R-376 and R-393.
Mutagenesis	357 – 357	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123, R-353, R-376 and R-393.
Mutagenesis	376 – 376	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123, R-353, R-357 and R-393.

Literature citations
De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders.
Jia X.; Zhang S.; Tan S.; Du B.; He M.; Qin H.; Chen J.; Duan X.; Luo J.; Chen F.; Ouyang L.; Wang J.; Chen G.; Yu B.; Zhang G.; Zhang Z.; Lyu Y.; Huang Y.; Jiao J.; Chen J.Y.H.; Swoboda K.J.; Agolini E.; Novelli A.; Leoni C.; Zampino G.; Cappuccio G.; Brunetti-Pierri N.; Gerard B.; Ginglinger E.; Richer J.; McMillan H.; White-Brown A.; Hoekzema K.; Bernier R.A.; Kurtz-Nelson E.C.; Earl R.K.; Meddens C.; Alders M.; Fuchs M.; Caumes R.; Brunelle P.; Smol T.; Kuehl R.; Day-Salvatore D.L.; Monaghan K.G.; Morrow M.M.; Eichler E.E.; Hu Z.; Yuan L.; Tan J.; Xia K.; Shen Y.; Guo H.;
Sci. Adv. 8:eabo7112-eabo7112(2022)
Cited for: FUNCTION; VARIANTS CYS-78; ILE-132; CYS-208; CYS-320 AND MET-366; CHARACTERIZATION OF VARIANTS CYS-78; ILE-132; CYS-208; CYS-320 AND MET-366;

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.