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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q63HN8: Variant p.Cys3997Tyr

E3 ubiquitin-protein ligase RNF213
Gene: RNF213
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Variant information Variant position: help 3997 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Cysteine (C) to Tyrosine (Y) at position 3997 (C3997Y, p.Cys3997Tyr). 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 (C) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 Rare variant detected in a sporadic case of Moyamoya disease in Caucasian population; abolished E3 ubiquitin-protein ligase activity. Any additional useful information about the variant.


Sequence information Variant position: help 3997 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 5207 The length of the canonical sequence.
Location on the sequence: help TLCECKETASKTLSRFGIQP C SICLGDAKDPVCLPCDHVHC 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                         TLCECKETASKTLSRFGIQPCSICLGDAKDPVCLPCDHVHC

Mouse                         TLCDCKDKASKKFSRFGIQPCFICHGDAQDPVCLPCDHVYC

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 – 5207 E3 ubiquitin-protein ligase RNF213
Zinc finger 3997 – 4036 RING-type
Binding site 3997 – 3997
Binding site 4000 – 4000
Binding site 4012 – 4012
Binding site 4014 – 4014
Binding site 4017 – 4017
Alternative sequence 1 – 4650 Missing. In isoform 4.
Alternative sequence 1064 – 5207 Missing. In isoform 3.
Mutagenesis 4014 – 4014 H -> N. Abolished E3 ubiquitin-protein ligase activity; does not affect ubiquitination of lipopolysaccharide.



Literature citations
Moyamoya disease patient mutations in the RING domain of RNF213 reduce its ubiquitin ligase activity and enhance NFkappaB activation and apoptosis in an AAA+ domain-dependent manner.
Takeda M.; Tezuka T.; Kim M.; Choi J.; Oichi Y.; Kobayashi H.; Harada K.H.; Mizushima T.; Taketani S.; Koizumi A.; Youssefian S.;
Biochem. Biophys. Res. Commun. 525:668-674(2020)
Cited for: FUNCTION; CATALYTIC ACTIVITY; PATHWAY; INTERACTION WITH UBE2N; CHARACTERIZATION OF VARIANTS TYR-3997; ARG-4007; ASN-4014; SER-4017; CYS-4019; ARG-4024; ARG-4032 AND LEU-4033; VARIANT MYMY2 ASN-4013; RNF213 rare variants in an ethnically diverse population with Moyamoya disease.
Cecchi A.C.; Guo D.; Ren Z.; Flynn K.; Santos-Cortez R.L.; Leal S.M.; Wang G.T.; Regalado E.S.; Steinberg G.K.; Shendure J.; Bamshad M.J.; Grotta J.C.; Nickerson D.A.; Pannu H.; Milewicz D.M.;
Stroke 45:3200-3207(2014)
Cited for: VARIANTS MYMY2 ASN-4013 AND LYS-4810; VARIANTS ALA-529 DEL; GLN-3922; TYR-3997; CYS-4019; VAL-4076; LYS-4115 DEL; GLU-4237; THR-4732 AND ILE-5163;
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.