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UniProtKB/Swiss-Prot P04637: Variant p.Ser376Thr

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

Variant position:  376
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Serine (S) to Threonine (T) at position 376 (S376T, p.Ser376Thr).
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 small size and polar (S) to medium size and polar (T)
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

Variant description:  In a sporadic cancer; somatic mutation.
Any additional useful information about the variant.

Sequence information

Variant position:  376
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  393
The length of the canonical sequence.

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.











Chicken                       APRPSKGRRV---KV-----EGPQPSCGKKLLQK----

Xenopus laevis                QQKVT--------IKCRKCRDEIKPKKGKKLLVKDEQ-


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.

Chain 1 – 393 Cellular tumor antigen p53
Region 300 – 393 Interaction with CARM1
Region 368 – 387 Basic (repression of DNA-binding)
Modified residue 370 – 370 N6,N6-dimethyllysine; alternate
Modified residue 370 – 370 N6-methyllysine; by SMYD2; alternate
Modified residue 372 – 372 N6-methyllysine; by SETD7
Modified residue 373 – 373 N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate
Modified residue 373 – 373 N6-acetyllysine; alternate
Modified residue 381 – 381 N6-acetyllysine
Modified residue 382 – 382 N6,N6-dimethyllysine; alternate
Modified residue 382 – 382 N6-acetyllysine; by KAT6A; alternate
Modified residue 382 – 382 N6-methyllysine; by KMT5A; alternate
Modified residue 392 – 392 Phosphoserine; by CK2, CDK2 and NUAK1
Cross 386 – 386 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Alternative sequence 342 – 393 Missing. In isoform 2, isoform 5 and isoform 8.
Alternative sequence 347 – 393 Missing. In isoform 3, isoform 6 and isoform 9.
Mutagenesis 359 – 359 P -> D. Abolishes binding to USP7.
Mutagenesis 361 – 361 G -> E. Abolishes binding to USP7.
Mutagenesis 362 – 362 S -> A. Abolishes binding to USP7.
Mutagenesis 370 – 370 K -> R. Induces a decrease in methylation by SMYD2.
Mutagenesis 372 – 372 K -> R. Induces a decrease in protein stabilization.
Mutagenesis 373 – 373 K -> R. Abolishes dimethylation by EHMT1 and EHMT2.
Mutagenesis 382 – 382 K -> A. Abolishes acetylation by CREBBP.
Mutagenesis 382 – 382 K -> R. Abolishes monomethylation by KMT5A.
Mutagenesis 383 – 383 L -> A. Abolishes S-315 phosphorylation by CDK2/cyclin A.
Mutagenesis 385 – 385 F -> A. Reduced SUMO1 conjugation.
Mutagenesis 386 – 386 K -> A. Abolishes SUMO1 conjugation, in vitro and in vivo.
Mutagenesis 387 – 387 T -> A. No effect SUMO1 conjugation.
Mutagenesis 388 – 388 E -> A. Abolishes SUMO1 conjugation.
Helix 375 – 380

Literature citations

No reference for the current variant in UniProtKB/Swiss-Prot.

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.