UniProtKB/Swiss-Prot O96017: Variant p.His371Tyr

Serine/threonine-protein kinase Chk2
Gene: CHEK2
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Variant information Variant position:

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

LB/B 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 Histidine (H) to Tyrosine (Y) at position 371 (H371Y, p.His371Tyr). 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 polar (H) to large size and aromatic (Y) 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:

Confers a moderate risk of breast cancer; partially reduces kinase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs531398630 [ dbSNP | Ensembl ]

Sequence information Variant position:

371 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:

ENVLLSSQEEDCLIKITDFG H SKILGETSLMRTLCGTPTYL 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                         ENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYL

Mouse                         ENVLLSSQEEDCLIKITDFGQSKILGETSLMRTLCGTPTYL

Caenorhabditis elegans        ENILCSDKAERCILKLTDFGMAK--NSVNRMKTRCGTPSYN

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
Binding site	368 – 368
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	368 – 368	D -> N. Loss of autophosphorylation activity.
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	369 – 371

Literature citations
A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.
Liu Y.; Liao J.; Xu Y.; Chen W.; Liu D.; Ouyang T.; Li J.; Wang T.; Fan Z.; Fan T.; Lin B.; Xu X.; Xie Y.;
Hum. Mutat. 32:1000-1003(2011)
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO BC; VARIANTS CYS-180 AND TYR-371; CHARACTERIZATION OF VARIANT TYR-371;

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.