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UniProtKB/Swiss-Prot P04637: Variant p.Leu252Pro

Cellular tumor antigen p53
Gene: TP53
Chromosomal location: 17p13.1
Variant information

Variant position:  252
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 Leucine (L) to Proline (P) at position 252 (L252P, p.Leu252Pro).
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:  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.



Sequence information

Variant position:  252
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:   IHYNYMCNSSCMGGMNRRPI  L TIITLEDSSGNLLGRNSFEV
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                         IHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV

                              IHYNYMCNSSCMGGMNRRPILTIITLEDSSGNVLGRNSFEV

Rhesus macaque                IHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV

Mouse                         IHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEV

Rat                           IHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEV

Pig                           IHYNFMCNSSCMGGMNRRPILTIITLEDASGNLLGRNSFEV

Bovine                        IHYNFMCNSSCMGGMNRRPILTIITLEDSCGNLLGRNSFEV

Rabbit                        IHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV

Sheep                         IHYNFMCNSSCMGGMNRRPILTIITLEDSRGNLLGRSSFEV

Cat                           IHYNFMCNSSCMGGMNRRPIITIITLEDSNGKLLGRNSFEV

Chicken                       VLYNFMCNSSCMGGMNRRPILTILTLEGPGGQLLGRRCFEV

Xenopus laevis                VLYNYMCNSSCMGGMNRRPILTIITLETPQGLLLGRRCFEV

Zebrafish                     VLLNYMCNSSCMGGMNRRPILTIITLETQEGQLLGRRSFEV

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.

TypePositionsDescription
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
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;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.