UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1073

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 Serine (S) to Arginine (R) at position 1073 (S1073R, p.Ser1073Arg).

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 small size and polar (S) to large size and basic (R)

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 FFEVF1; inhibits slightly DEPDC5 signaling; does not change kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs754608531 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1073

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

Protein sequence length:

1603

The length of the canonical sequence.

Location on the sequence:

CLGEQQAAVHGGKSSAQSAE S SSVAMTPTYMDSPRKDGAFF

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                         CLGEQQAAVHGGKSSAQSAESSSVAMTPTYMDSPRKDGAFF

Mouse                         SLGEQQTTVHG-KSSTQPAENSSVAMTPTYVDSPRKDGAFF

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 – 1603	GATOR complex protein DEPDC5
Alternative sequence	560 – 1603	Missing. In isoform 2.
Mutagenesis	1065 – 1065	K -> R. No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1088 and R-1574.
Mutagenesis	1088 – 1088	K -> R. No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1065 and R-1574.

Literature citations

Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
Dibbens L.M.; de Vries B.; Donatello S.; Heron S.E.; Hodgson B.L.; Chintawar S.; Crompton D.E.; Hughes J.N.; Bellows S.T.; Klein K.M.; Callenbach P.M.; Corbett M.A.; Gardner A.E.; Kivity S.; Iona X.; Regan B.M.; Weller C.M.; Crimmins D.; O'Brien T.J.; Guerrero-Lopez R.; Mulley J.C.; Dubeau F.; Licchetta L.; Bisulli F.; Cossette P.; Thomas P.Q.; Gecz J.; Serratosa J.; Brouwer O.F.; Andermann F.; Andermann E.; van den Maagdenberg A.M.; Pandolfo M.; Berkovic S.F.; Scheffer I.E.;
Nat. Genet. 45:546-551(2013)
Cited for: VARIANTS FFEVF1 VAL-452; ARG-1073 AND LEU-1104; INVOLVEMENT IN FFEVF1;

Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy.
van Kranenburg M.; Hoogeveen-Westerveld M.; Nellist M.;
Hum. Mutat. 36:200-209(2015)
Cited for: VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452; GLN-485; MET-864; ARG-1073 AND GLY-1162; CHARACTERIZATION OF VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452; GLN-485; MET-864; ARG-1073 AND GLY-1162; IDENTIFICATION IN GATOR COMPLEX;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75140: Variant p.Ser1073Arg