UniProtKB/SwissProt variant VAR

Variant information

Variant position:

248

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 Arginine (R) to Tryptophan (W) at position 248 (R248W, p.Arg248Trp).

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 large size and basic (R) to large size and aromatic (W)

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 LFS; germline mutation and in sporadic cancers; somatic mutation; no effect on susceptibility to calpain.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121912651 [ dbSNP | Ensembl ]

Sequence information

Variant position:

248

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:

DCTTIHYNYMCNSSCMGGMN R RPILTIITLEDSSGNLLGRN

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                         DCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRN

                              DYTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNVLGRN

Rhesus macaque                DCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRN

Mouse                         EYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRD

Rat                           DYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRD

Pig                           DCTTIHYNFMCNSSCMGGMNRRPILTIITLEDASGNLLGRN

Bovine                        ECTTIHYNFMCNSSCMGGMNRRPILTIITLEDSCGNLLGRN

Rabbit                        DCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRN

Sheep                         ECTTIHYNFMCNSSCMGGMNRRPILTIITLEDSRGNLLGRS

Cat                           DCTTIHYNFMCNSSCMGGMNRRPIITIITLEDSNGKLLGRN

Chicken                       DCTTVLYNFMCNSSCMGGMNRRPILTILTLEGPGGQLLGRR

Xenopus laevis                ECTTVLYNYMCNSSCMGGMNRRPILTIITLETPQGLLLGRR

Zebrafish                     EWTTVLLNYMCNSSCMGGMNRRPILTIITLETQEGQLLGRR

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	241 – 248	Interaction with the 53BP2 SH3 domain
Metal binding	238 – 238	Zinc
Metal binding	242 – 242	Zinc
Mutagenesis	248 – 248	R -> S. Does not induce SNAI1 degradation.
Turn	243 – 248

Literature citations

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.
Malkin D.; Li F.P.; Strong L.C.; Fraumeni J.F. Jr.; Nelson C.E.; Kim D.H.; Kassel J.; Gryka M.A.; Bischoff F.Z.; Tainsky M.A.; Friend S.H.;
Science 250:1233-1238(1990)
Cited for: VARIANTS LFS CYS-245; TRP-248; PRO-252 AND LYS-258;

Molecular analysis of the TP53 gene in Barrett's adenocarcinoma.
Audrezet M.-P.; Robaszkiewicz M.; Mercier B.; Nousbaum J.-B.; Hardy E.; Bail J.-P.; Volant A.; Lozac'H P.; Gouerou H.; Ferec C.;
Hum. Mutat. 7:109-113(1996)
Cited for: VARIANTS SPORADIC CANCERS PHE-176; SER-245; TRP-248; TRP-282 AND GLN-286;

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: VARIANTS [LARGE SCALE ANALYSIS] LEU-134; PHE-157; CYS-163; HIS-175; ARG-177; ARG-193; PRO-213; PHE-241; PHE-242; GLN-248; TRP-248; SER-249; TRP-267; LYS-271; CYS-273; HIS-273; LEU-273; SER-278; ILE-280 AND HIS-281;

Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3.
Guan Y.; Huang D.; Chen F.; Gao C.; Tao T.; Shi H.; Zhao S.; Liao Z.; Lo L.J.; Wang Y.; Chen J.; Peng J.;
PLoS Biol. 14:e1002555-e1002555(2016)
Cited for: CHARACTERIZATION OF VARIANTS VAL-138; HIS-175; ILE-237; TRP-248 AND PRO-273;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04637: Variant p.Arg248Trp