UniProtKB/Swiss-Prot Q63HN8: Variant p.Pro4007Arg

E3 ubiquitin-protein ligase RNF213
Gene: RNF213
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Variant information Variant position:

4007 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Proline (P) to Arginine (R) at position 4007 (P4007R, p.Pro4007Arg). 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 medium size and hydrophobic (P) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

Rare variant detected in a sporadic case of Moyamoya disease in East Asian population; abolished E3 ubiquitin-protein ligase activity. Any additional useful information about the variant.

Sequence information Variant position:

4007 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

5207 The length of the canonical sequence.
Location on the sequence:

KTLSRFGIQPCSICLGDAKD P VCLPCDHVHCLRCLRAWFAS 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                         KTLSRFGIQPCSICLGDAKDPVCLPCDHVHCLRCLRAWFAS

Mouse                         KKFSRFGIQPCFICHGDAQDPVCLPCDHVYCLRCIQTWLIP

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 – 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
Binding site	4020 – 4020
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.
Mutagenesis	4024 – 4024	W -> R. 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; Molecular analysis of RNF213 gene for moyamoya disease in the Chinese Han population.
Wu Z.; Jiang H.; Zhang L.; Xu X.; Zhang X.; Kang Z.; Song D.; Zhang J.; Guan M.; Gu Y.;
PLoS ONE 7:E48179-E48179(2012)
Cited for: VARIANTS MYMY2 THR-4399 AND LYS-4810; VARIANTS ARG-4007; LEU-4367; PRO-4586; VAL-4631; ASP-4950; VAL-5021 AND ILE-5136;

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.