UniProtKB/SwissProt variant VAR

Variant information

Variant position:

258

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 Glutamate (E) to Lysine (K) at position 258 (E258K, p.Glu258Lys).

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 acidic (E) to large size and basic (K)

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

Involvement in disease:

Li-Fraumeni syndrome (LFS) [MIM:151623]: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269|PubMed:10484981, ECO:0000269|PubMed:1565144, ECO:0000269|PubMed:1737852, ECO:0000269|PubMed:1933902, ECO:0000269|PubMed:1978757, ECO:0000269|PubMed:2259385, ECO:0000269|PubMed:7887414, ECO:0000269|PubMed:8825920, ECO:0000269|PubMed:9452042}. Note=The disease is 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 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 rs121912652 [ dbSNP | Ensembl ]

Sequence information

Variant position:

258

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:

CNSSCMGGMNRRPILTIITL E DSSGNLLGRNSFEVRVCACP

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                         CNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACP

                              CNSSCMGGMNRRPILTIITLEDSSGNVLGRNSFEVRVCACP

Rhesus macaque                CNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACP

Mouse                         CNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACP

Rat                           CNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACP

Pig                           CNSSCMGGMNRRPILTIITLEDASGNLLGRNSFEVRVCACP

Bovine                        CNSSCMGGMNRRPILTIITLEDSCGNLLGRNSFEVRVCACP

Rabbit                        CNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACP

Sheep                         CNSSCMGGMNRRPILTIITLEDSRGNLLGRSSFEVRVCACP

Cat                           CNSSCMGGMNRRPIITIITLEDSNGKLLGRNSFEVRVCACP

Chicken                       CNSSCMGGMNRRPILTILTLEGPGGQLLGRRCFEVRVCACP

Xenopus laevis                CNSSCMGGMNRRPILTIITLETPQGLLLGRRCFEVRVCACP

Zebrafish                     CNSSCMGGMNRRPILTIITLETQEGQLLGRRSFEVRVCACP

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
Metal binding	238 – 238	Zinc
Metal binding	242 – 242	Zinc
Modified residue	269 – 269	Phosphoserine; by AURKB
Mutagenesis	248 – 248	R -> S. Does not induce SNAI1 degradation.
Mutagenesis	269 – 269	S -> A. Abolishes phosphorylation.
Mutagenesis	269 – 269	S -> E. Inhibits strongly its transcriptional activity.
Beta strand	251 – 258

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04637: Variant p.Glu258Lys