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UniProtKB/Swiss-Prot P04637: Variant p.Arg175His

Cellular tumor antigen p53
Gene: TP53
Variant information

Variant position:  175
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 175 (R175H, p.Arg175His).
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; does not induce SNAI1 degradation; reduces interaction with ZNF385A; loss of susceptibility to calpain.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  175
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:   TRVRAMAIYKQSQHMTEVVR  R CPHHERCSDSDGLAPPQHLI
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                         TRVRAMAIYKQSQHMTEVVRRCPHHERCSD-SDGLAPPQHLI

                              TCVRAMAIYKKSEFVTEVVRRCPHHERCSDSSDGLAPPQHL

Rhesus macaque                SRVRAMAIYKQSQHMTEVVRRCPHHERCSD-SDGLAPPQHL

Mouse                         SRVRAMAIYKKSQHMTEVVRRCPHHERCSD-GDGLAPPQHL

Rat                           TRVRAMAIYKKSQHMTEVVRRCPHHERCSD-GDGLAPPQHL

Pig                           TRVRAMAIYKKSEYMTEVVRRCPHHERSSDYSDGLAPPQHL

Bovine                        TRVRAMAIYKKLEHMTEVVRRCPHHERSSDYSDGLAPPQHL

Rabbit                        TRVRAMAIYKKSQHMTEVVRRCPHHERCSD-SDGLAPPQHL

Sheep                         TRVRAMAIYKKLEHMTEVVRRSPHHERSSDYSDGLAPPQHL

Cat                           TCVRAMAIYKKSEFMTEVVRRCPHHERCPDSSDGLAPPQHL

Chicken                       SSLRAVAVYKKSEHVAEVVRRCPHHERCGGGTDGLAPAQHL

Xenopus laevis                SILRATAVYKKSEHVAEVVKRCPHHERSVEPGEDAAPPSHL

Zebrafish                     SVVRATAIYKKSEHVAEVVRRCPHHERTPD-GDNLAPAGHL

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 113 – 236 Required for interaction with FBXO42
Region 116 – 292 Interaction with AXIN1
Metal binding 176 – 176 Zinc
Metal binding 179 – 179 Zinc
Modified residue 183 – 183 Phosphoserine; by AURKB
Mutagenesis 183 – 183 S -> A. Abolishes strongly phosphorylation.
Mutagenesis 183 – 183 S -> E. Inhibits slightly its transcriptional activity.


Literature citations

Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation.
Das S.; Raj L.; Zhao B.; Kimura Y.; Bernstein A.; Aaronson S.A.; Lee S.W.;
Cell 130:624-637(2007)
Cited for: INTERACTION WITH ZNF385A; CHARACTERIZATION OF VARIANTS ALA-143; HIS-175 AND PRO-175;

p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma.
Lim S.O.; Kim H.; Jung G.;
FEBS Lett. 584:2231-2236(2010)
Cited for: INTERACTION WITH SNAI1; CHARACTERIZATION OF VARIANTS LEU-110; PRO-155; HIS-175; SER-232; SER-249; HIS-273 AND TRP-282; MUTAGENESIS OF ARG-248;

p53 gene mutations in Barrett's epithelium and esophageal cancer.
Casson A.G.; Mukhopadhyay T.; Cleary K.R.; Ro J.Y.; Levin B.; Roth J.A.;
Cancer Res. 51:4495-4499(1991)
Cited for: VARIANTS SPORADIC CANCERS LEU-152; ALA-155; HIS-175; PHE-176 AND HIS-273;

Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.
Frebourg T.; Barbier N.; Yan Y.-X.; Garber J.E.; Dreyfus M.; Fraumeni J.F. Jr.; Li F.P.; Friend S.H.;
Am. J. Hum. Genet. 56:608-615(1995)
Cited for: VARIANTS LFS HIS-175; ARG-193; GLN-248; CYS-273 AND TYR-275;

An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53.
Varley J.M.; McGrown G.; Thorncroft M.; Tricker K.J.; Teare M.D.; Santibanez-Koref M.F.; Houlston R.S.; Martin J.; Birch J.M.; Evans D.G.R.;
J. Med. Genet. 32:942-945(1995)
Cited for: VARIANT LFS HIS-175;

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;

Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3.
Guan Y.; Huang D.; Chen F.; Gao C.; Tao T.; Shi H.; Zhao S.; Liao Z.; Lo L.J.; Wang Y.; Chen J.; Peng J.;
PLoS Biol. 14:e1002555-e1002555(2016)
Cited for: CHARACTERIZATION OF VARIANTS VAL-138; HIS-175; ILE-237; TRP-248 AND PRO-273;

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.