UniProtKB/SwissProt variant VAR

Variant information

Variant position:

275

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 Cysteine (C) to Tyrosine (Y) at position 275 (C275Y, p.Cys275Tyr).

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 medium size and polar (C) to large size and aromatic (Y)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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 LFS; germline mutation and in sporadic cancers; somatic mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs863224451 [ dbSNP | Ensembl ]

Sequence information

Variant position:

275

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

Protein sequence length:

393

The length of the canonical sequence.

Location on the sequence:

ITLEDSSGNLLGRNSFEVRV C ACPGRDRRTEEENLRKKGEP

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                         ITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEP

                              ITLEDSSGNVLGRNSFEVRVCACPGRDRRTEEENFHKKGEP

Rhesus macaque                ITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKGEP

Mouse                         ITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVL

Rat                           ITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEEH

Pig                           ITLEDASGNLLGRNSFEVRVCACPGRDRRTEEENFLKKGQS

Bovine                        ITLEDSCGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGQS

Rabbit                        ITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKGEP

Sheep                         ITLEDSRGNLLGRSSFEVRVCACPGRDRRTEEENFRKKGQS

Cat                           ITLEDSNGKLLGRNSFEVRVCACPGRDRRTEEENFRKKGEP

Chicken                       LTLEGPGGQLLGRRCFEVRVCACPGRDRKIEEENFRKRGGA

Xenopus laevis                ITLETPQGLLLGRRCFEVRVCACPGRDRRTEEDNYTKKRGL

Zebrafish                     ITLETQEGQLLGRRSFEVRVCACPGRDRKTEESNFKKDQET

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 – 393	Cellular tumor antigen p53
DNA binding	102 – 292
Region	1 – 320	Interaction with CCAR2
Region	100 – 370	Interaction with HIPK1
Region	100 – 300	Required for interaction with ZNF385A
Region	116 – 292	Interaction with AXIN1
Region	256 – 294	Interaction with E4F1
Region	273 – 280	Interaction with DNA
Modified residue	269 – 269	Phosphoserine; by AURKB
Modified residue	284 – 284	Phosphothreonine; by AURKB
Cross	291 – 291	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	292 – 292	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	269 – 269	S -> A. Abolishes phosphorylation.
Mutagenesis	269 – 269	S -> E. Inhibits strongly its transcriptional activity.
Mutagenesis	284 – 284	T -> E. Inhibits strongly its transcriptional activity.

Literature citations

Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.
Frebourg T.; Barbier N.; Yan Y.-X.; Garber J.E.; Dreyfus M.; Fraumeni J.F. Jr.; Li F.P.; Friend S.H.;
Am. J. Hum. Genet. 56:608-615(1995)
Cited for: VARIANTS LFS HIS-175; ARG-193; GLN-248; CYS-273 AND TYR-275;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04637: Variant p.Cys275Tyr