UniProtKB/SwissProt variant VAR

Variant information

Variant position:

12

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Glycine (G) to Valine (V) at position 12 (G12V, p.Gly12Val).

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 hydrophobic (V)

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 CSTLO, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894230 [ dbSNP | Ensembl ]

Sequence information

Variant position:

12

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

Protein sequence length:

189

The length of the canonical sequence.

Location on the sequence:

MTEYKLVVVGA G GVGKSALTIQLIQNHFVDEY

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                         MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEY

Mouse                         MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEY

Rat                           MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEY

Chicken                       MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEY

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 – 186	GTPase HRas
Initiator methionine	1 – 1	Removed; alternate
Chain	2 – 186	GTPase HRas, N-terminally processed
Nucleotide binding	10 – 17	GTP
Modified residue	1 – 1	N-acetylmethionine; in GTPase HRas; alternate
Modified residue	2 – 2	N-acetylthreonine; in GTPase HRas, N-terminally processed
Mutagenesis	17 – 17	S -> N. Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. No effect on subcellular location of isoform 2.
Mutagenesis	26 – 26	N -> G. Loss of interaction with PLCE1; when associated with V-12.
Mutagenesis	29 – 29	V -> A. No effect on interaction with PLCE1; when associated with V-12.
Mutagenesis	32 – 32	Y -> F. Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12.
Beta strand	12 – 15

Literature citations

Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras.
Song C.; Hu C.-D.; Masago M.; Kariya K.; Yamawaki-Kataoka Y.; Shibatohge M.; Wu D.; Satoh T.; Kataoka T.;
J. Biol. Chem. 276:2752-2757(2001)
Cited for: INTERACTION WITH PLCE1; CHARACTERIZATION OF VARIANT VAL-12; MUTAGENESIS OF SER-17; ASN-26; VAL-29; TYR-32; PRO-34; THR-35; GLU-37; ASP-38 AND SER-39;

Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease.
Liu F.; Iqbal K.; Grundke-Iqbal I.; Rossie S.; Gong C.X.;
J. Biol. Chem. 280:1790-1796(2005)
Cited for: CHARACTERIZATION OF CSTLO VARIANT VAL-12;

Germline mutations in HRAS proto-oncogene cause Costello syndrome.
Aoki Y.; Niihori T.; Kawame H.; Kurosawa K.; Ohashi H.; Tanaka Y.; Filocamo M.; Kato K.; Suzuki Y.; Kure S.; Matsubara Y.;
Nat. Genet. 37:1038-1040(2005)
Cited for: VARIANTS CSTLO ALA-12; SER-12; VAL-12 AND ASP-13;

Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation.
van der Burgt I.; Kupsky W.; Stassou S.; Nadroo A.; Barroso C.; Diem A.; Kratz C.P.; Dvorsky R.; Ahmadian M.R.; Zenker M.;
J. Med. Genet. 44:459-462(2007)
Cited for: VARIANTS CMEMS VAL-12; SER-12; LYS-22 AND LYS-63;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01112: Variant p.Gly12Val