UniProtKB/SwissProt variant VAR

Variant information

Variant position:

337

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

Type of variant:

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:

From Arginine (R) to Histidine (H) at position 337 (R337H, p.Arg337His).

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 large size and basic (R) to medium size and polar (H)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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 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 rs121912664 [ dbSNP | Ensembl ]

Sequence information

Variant position:

337

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:

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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QPK----KK----PLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGK

                              PQK----KK----PLDGEYFTLQIRGRERYEMFRNLNEALE

Rhesus macaque                QPK----KK----PLDGEYFTLQIRGRERFEMFRELNEALE

Mouse                         PQK----KK----PLDGEYFTLKIRGRKRFEMFRELNEALE

Rat                           QQK----KK----PLDGEYFTLKIRGRERFEMFRELNEALE

Pig                           VQK----KK----PLDGEYFTLQIRGRERFEMFRELNDALE

Bovine                        QPK----KK----PLDGEYFTLQIRGFKRYEMFRELNDALE

Rabbit                        QTK----KK----PLDGEYFILKIRGRERFEMFRELNEALE

Sheep                         QQK----KK----PLDGEYFTLQIRGRKRFEMFRELNEALE

Cat                           PQK----KK----PLDGEYFTLQIRGRERFEMFRELNEALE

Chicken                       PPK----KR--VLNPDNEIFYLQVRGRRRYEMLKEINEALQ

Xenopus laevis                LPK----KRLVVVDDDEEIFTLRIKGRSRYEMIKKLNDALE

Zebrafish                     RPEGSKKAK--GSSSDEEIFTLQVRGRERYEILKKLNDSLE

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
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
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

An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
Ribeiro R.C.; Sandrini F.; Figueiredo B.; Zambetti G.P.; Michalkiewicz E.; Lafferty A.R.; DeLacerda L.; Rabin M.; Cadwell C.; Sampaio G.; Cat I.; Stratakis C.A.; Sandrini R.;
Proc. Natl. Acad. Sci. U.S.A. 98:9330-9335(2001)
Cited for: VARIANT ADCC HIS-337;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04637: Variant p.Arg337His