UniProtKB/Swiss-Prot O00571: Variant p.Arg528His

ATP-dependent RNA helicase DDX3X
Gene: DDX3X
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Variant information Variant position:

528 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 Arginine (R) to Histidine (H) at position 528 (R528H, p.Arg528His). 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 medulloblastoma; somatic mutation; loss of ATPase activity; interacts with CSNK1E, even in the presence of dsRNA; contrary to wild-type protein, strongly interacts with CSNK1A1 and CSNK1D in vivo; strongly increased ability to activate CSNK1E kinase activity, leading to increased DVL phosphorylation, thereby activating Wnt/beta-catenin signaling; no effect on RNA-binding, nor on subcellular location. Any additional useful information about the variant.

Sequence information Variant position:

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

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

SNVKHVINFDLPSDIEEYVH R IGRTGRVGNLGLATSFFNER 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                         SNVKHVINFDLPSDIEEYVHRIGRTGRVGNLGLATSFFNER

Mouse                         SNVKHVINFDLPSDIEEYVHRIGRTGRVGNLGLATSFFNER

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	2 – 662	ATP-dependent RNA helicase DDX3X
Domain	414 – 575	Helicase C-terminal
Region	100 – 662	Interaction with GSK3B
Region	409 – 662	Interaction with HCV core protein
Modified residue	520 – 520	Phosphoserine; by TBK1; in vitro
Modified residue	542 – 542	Phosphothreonine; by TBK1; in vitro
Modified residue	543 – 543	Phosphoserine; by CSNK1E and TBK1; in vitro
Mutagenesis	520 – 520	S -> A. Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-442 and A-456.
Helix	522 – 529

Literature citations
A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1epsilon.
Dolde C.; Bischof J.; Grueter S.; Montada A.; Halekotte J.; Peifer C.; Kalbacher H.; Baumann U.; Knippschild U.; Suter B.;
J. Cell Sci. 131:0-0(2018)
Cited for: FUNCTION; INTERACTION WITH CSNK1E AND CSNK1D; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-429; THR-469; SER-470 AND SER-543; CHARACTERIZATION OF VARIANTS MEDULLOBLASTOMA CYS-376 AND HIS-528;

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.