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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UNE7: Variant p.Thr246Met

E3 ubiquitin-protein ligase CHIP
Gene: STUB1
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Variant information Variant position: help 246 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 Threonine (T) to Methionine (M) at position 246 (T246M, p.Thr246Met). 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 medium size and polar (T) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In SCAR16; inhibits ubiquitin ligase activity and autoubiquitination. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 246 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 303 The length of the canonical sequence.
Location on the sequence: help DIPDYLCGKISFELMREPCI T PSGITYDRKDIEEHLQRVGH 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                         DIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGH

Mouse                         DIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGH

Chicken                       DIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGH
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 – 303 E3 ubiquitin-protein ligase CHIP
Domain 226 – 300 U-box
Region 143 – 303 Required for ubiquitination of FOXO1
Cross 255 – 255 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 260 – 260 H -> Q. Loss of ability to ubiquitinate FOXP3 and SIRT6. Abolishes STUB1-mediated degradation of CHRNA3. Abolishes autoubiquitination and ubiquitination of ICER-type isoforms of CREM. Reduces interaction, ubiquitination and proteasomal degradation of NFATC3. No effect on localization to the mitochondria following oxygen and glucose deprivation-induced cellular stress.



Literature citations
Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.
Shi C.H.; Schisler J.C.; Rubel C.E.; Tan S.; Song B.; McDonough H.; Xu L.; Portbury A.L.; Mao C.Y.; True C.; Wang R.H.; Wang Q.Z.; Sun S.L.; Seminara S.B.; Patterson C.; Xu Y.M.;
Hum. Mol. Genet. 23:1013-1024(2014)
Cited for: VARIANT SCAR16 MET-246; STUB1 mutations in autosomal recessive ataxias - evidence for mutation-specific clinical heterogeneity.
Heimdal K.; Sanchez-Guixe M.; Aukrust I.; Bollerslev J.; Bruland O.; Jablonski G.E.; Erichsen A.K.; Gude E.; Koht J.A.; Erdal S.; Fiskerstrand T.; Haukanes B.I.; Boman H.; Bjoerkhaug L.; Tallaksen C.M.; Knappskog P.M.; Johansson S.;
Orphanet J. Rare Dis. 9:146-146(2014)
Cited for: VARIANTS SCAR16 LYS-28; SER-65 AND MET-246; CHARACTERIZATION OF VARIANTS SCAR16 LYS-28; SER-65 AND MET-246;
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.