UniProtKB/SwissProt variant VAR

Variant information

Variant position:

393

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

Type of variant:

Unclassified

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 Proline (P) to Leucine (L) at position 393 (P393L, p.Pro393Leu).

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:

-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

Involvement in disease:

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:16959974}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In a colorectal cancer sample; somatic mutation.

Any additional useful information about the variant.

Sequence information

Variant position:

393

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

Protein sequence length:

425

The length of the canonical sequence.

Location on the sequence:

RMSFVKGWGAEYRRQTVTST P CWIELHLNGPLQWLDKVLTQ

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                         RMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQ

Mouse                         RMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQ

Rat                           RMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQ

Pig                           RMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQ

Chicken                       RMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQ

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 – 425	Mothers against decapentaplegic homolog 3
Domain	232 – 425	MH2
Modified residue	378 – 378	N6-acetyllysine
Mutagenesis	378 – 378	K -> Q. Increased transcriptional activity. No further increase in transcriptional activity with EP300.
Mutagenesis	378 – 378	K -> R. Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409.
Mutagenesis	409 – 409	K -> R. No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378.
Beta strand	392 – 400

Literature citations

The consensus coding sequences of human breast and colorectal cancers.
Sjoeblom T.; Jones S.; Wood L.D.; Parsons D.W.; Lin J.; Barber T.D.; Mandelker D.; Leary R.J.; Ptak J.; Silliman N.; Szabo S.; Buckhaults P.; Farrell C.; Meeh P.; Markowitz S.D.; Willis J.; Dawson D.; Willson J.K.V.; Gazdar A.F.; Hartigan J.; Wu L.; Liu C.; Parmigiani G.; Park B.H.; Bachman K.E.; Papadopoulos N.; Vogelstein B.; Kinzler K.W.; Velculescu V.E.;
Science 314:268-274(2006)
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-393; INVOLVEMENT IN COLORECTAL CANCER;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P84022: Variant p.Pro393Leu