UniProtKB/SwissProt variant VAR

Variant information

Variant position:

390

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Tyrosine (Y) to Cysteine (C) at position 390 (Y390C, p.Tyr390Cys).

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 aromatic (Y) to medium size and polar (C)

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

Involvement in disease:

Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12094328, ECO:0000269|PubMed:21618645, ECO:0000269|PubMed:25619829}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In BC; does not phosphorylate p53/TP53.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs200928781 [ dbSNP | Ensembl ]

Sequence information

Variant position:

390

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

543

The length of the canonical sequence.

Location on the sequence:

GHSKILGETSLMRTLCGTPT Y LAPEVLVSVGTAGYNRAVDC

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                         GHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDC

Mouse                         GQSKILGETSLMRTLCGTPTYLAPEVLVSNGTAGYSRAVDC

Caenorhabditis elegans        GMAK--NSVNRMKTRCGTPSYNAPEIVANEGVE-YTPKVDI

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 – 543	Serine/threonine-protein kinase Chk2
Domain	220 – 486	Protein kinase
Region	368 – 394	T-loop/activation segment
Modified residue	379 – 379	Phosphoserine; by autocatalysis
Modified residue	383 – 383	Phosphothreonine; by autocatalysis
Modified residue	387 – 387	Phosphothreonine; by autocatalysis
Alternative sequence	75 – 392	Missing. In isoform 11.
Alternative sequence	107 – 487	Missing. In isoform 3.
Alternative sequence	148 – 543	Missing. In isoform 10.
Alternative sequence	166 – 543	Missing. In isoform 6.
Alternative sequence	204 – 543	Missing. In isoform 5.
Alternative sequence	235 – 543	Missing. In isoform 2.
Alternative sequence	290 – 543	Missing. In isoform 8.
Alternative sequence	340 – 543	Missing. In isoform 7.
Mutagenesis	379 – 379	S -> A. Abrogates autophosphorylation at Ser-379 and prevents ubiquitination.
Mutagenesis	383 – 383	T -> A. Loss of phosphorylation in response to ionizing radiation.
Mutagenesis	387 – 387	T -> A. Loss of phosphorylation in response to ionizing radiation.
Helix	388 – 390

Literature citations

A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast cancer patients impairs its activity and is associated with increased breast cancer risk.
Wang N.; Ding H.; Liu C.; Li X.; Wei L.; Yu J.; Liu M.; Ying M.; Gao W.; Jiang H.; Wang Y.;
Oncogene 34:5198-5205(2015)
Cited for: VARIANT BC CYS-390; CHARACTERIZATION OF VARIANT BC CYS-390; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O96017: Variant p.Tyr390Cys