UniProtKB/SwissProt variant VAR

Variant information

Variant position:

278

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 Proline (P) to Serine (S) at position 278 (P278S, p.Pro278Ser).

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 hydrophobic (P) to small size and polar (S)

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 rs17849781 [ dbSNP | Ensembl ]

Sequence information

Variant position:

278

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:

EDSSGNLLGRNSFEVRVCAC P GRDRRTEEENLRKKGEPHHE

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                         EDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPH--HE

                              EDSSGNVLGRNSFEVRVCACPGRDRRTEEENFHKKGEPC--

Rhesus macaque                EDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKGEPC--

Mouse                         EDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLC--

Rat                           EDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEEHC--

Pig                           EDASGNLLGRNSFEVRVCACPGRDRRTEEENFLKKGQSC--

Bovine                        EDSCGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGQSC--

Rabbit                        EDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKGEPC--

Sheep                         EDSRGNLLGRSSFEVRVCACPGRDRRTEEENFRKKGQSC--

Cat                           EDSNGKLLGRNSFEVRVCACPGRDRRTEEENFRKKGEPC--

Chicken                       EGPGGQLLGRRCFEVRVCACPGRDRKIEEENFRKRGGAG--

Xenopus laevis                ETPQGLLLGRRCFEVRVCACPGRDRRTEEDNYTKKRGLK--

Zebrafish                     ETQEGQLLGRRSFEVRVCACPGRDRKTEESNFKKDQETKTM

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.
Helix	278 – 287

Literature citations

Frequent mutation of the p53 gene in human esophageal cancer.
Hollstein M.C.; Metcalf R.A.; Welsh J.A.; Montesano R.; Harris C.C.;
Proc. Natl. Acad. Sci. U.S.A. 87:9958-9961(1990)
Cited for: VARIANTS SPORADIC CANCER VAL-154; VAL-245; GLN-248; LEU-278 AND SER-278;

Detection of p53 gene mutations in oral squamous cell carcinomas of a black African population sample.
van Rensburg E.J.; Engelbrecht S.; van Heerden W.F.P.; Kotze M.J.; Raubenheimer E.J.;
Hum. Mutat. 11:39-44(1998)
Cited for: VARIANTS SER-152; ILE-169; PHE-176; THR-195; CYS-220; ILE-230; CYS-273 AND SER-278;

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;

UniProtKB/Swiss-Prot P04637: Variant p.Pro278Ser