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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04637: Variant p.Arg337Cys

Cellular tumor antigen p53
Gene: TP53
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Variant information Variant position: help 337 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Cysteine (C) at position 337 (R337C, p.Arg337Cys). 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: help Change from large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In LFS; germline mutation and in sporadic cancers; somatic mutation; impaired ability to tetramerize and undergo liquid-liquid phase separation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 337 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 393 The length of the canonical sequence.
Location on the sequence: help QPKKKPLDGEYFTLQIRGRE R FEMFRELNEALELKDAQAGK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QPK--KKPL----DGEYFTLQIRGRERFEMFRELNEALELKDAQAGK

                              PQK--KKPL----DGEYFTLQIRGRERYEMFRNLNEALELK

Rhesus macaque                QPK--KKPL----DGEYFTLQIRGRERFEMFRELNEALELK

Mouse                         PQK--KKPL----DGEYFTLKIRGRKRFEMFRELNEALELK

Rat                           QQK--KKPL----DGEYFTLKIRGRERFEMFRELNEALELK

Pig                           VQK--KKPL----DGEYFTLQIRGRERFEMFRELNDALELK

Bovine                        QPK--KKPL----DGEYFTLQIRGFKRYEMFRELNDALELK

Rabbit                        QTK--KKPL----DGEYFILKIRGRERFEMFRELNEALELK

Sheep                         QQK--KKPL----DGEYFTLQIRGRKRFEMFRELNEALELM

Cat                           PQK--KKPL----DGEYFTLQIRGRERFEMFRELNEALELK

Chicken                       PPK--KRVL--NPDNEIFYLQVRGRRRYEMLKEINEALQLA

Xenopus laevis                LPK--KRLVVVDDDEEIFTLRIKGRSRYEMIKKLNDALELQ

Zebrafish                     RPEGSKKAKGSSSDEEIFTLQVRGRERYEILKKLNDSLELS
Sequence annotation in neighborhood: help 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
Region 100 – 370 Interaction with HIPK1
Region 300 – 393 Interaction with CARM1
Region 319 – 360 Interaction with HIPK2
Region 325 – 356 Oligomerization
Modified residue 321 – 321 N6-acetyllysine
Modified residue 333 – 333 Omega-N-methylarginine; by PRMT5
Modified residue 335 – 335 Symmetric dimethylarginine; by PRMT5
Modified residue 337 – 337 Symmetric dimethylarginine; by PRMT5
Cross 351 – 351 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 357 – 357 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence 332 – 346 IRGRERFEMFRELNE -> MLLDLRWCYFLINSS. In isoform 3, isoform 6 and isoform 9.
Alternative sequence 332 – 341 IRGRERFEMF -> DQTSFQKENC. In isoform 2, isoform 5 and isoform 8.
Mutagenesis 319 – 319 K -> A. Loss of nuclear localization; when associated with A-320 and A-321.
Mutagenesis 320 – 320 K -> A. Loss of nuclear localization; when associated with A-319 and A-321.
Mutagenesis 321 – 321 K -> A. Loss of nuclear localization; when associated with A-319 and A-320.
Mutagenesis 333 – 337 RGRER -> KGKEK. Reduced methylation by PRMT5. Reduced nuclear localization. Decreased binding to promoters of target genes. Reduced transcriptional activity. Decrease in cell cycle arrest.
Helix 335 – 354



Literature citations
Phase separation of p53 induced by its unstructured basic region and prevented by oncogenic mutations in tetramerization domain.
Chen C.; Fu G.; Guo Q.; Xue S.; Luo S.Z.;
Int. J. Biol. Macromol. 222:207-216(2022)
Cited for: DOMAIN; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS LFS CYS-337; HIS-337 AND PRO-344; CHARACTERIZATION OF VARIANT PRO-337; A germline missense mutation R337C in exon 10 of the human p53 gene.
Luca J.W.; Strong L.C.; Hansen M.F.;
Hum. Mutat. Suppl. 1:S58-S61(1998)
Cited for: VARIANT NON-CLASSICAL LFS CYS-337;
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.