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UniProtKB/Swiss-Prot O96017: Variant p.His371Tyr

Serine/threonine-protein kinase Chk2
Gene: CHEK2
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.

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.

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.




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.

Chain 1 – 543 Serine/threonine-protein kinase Chk2
Domain 220 – 486 Protein kinase
Region 368 – 394 T-loop/activation segment
Binding site 368 – 368 ATP
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)

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.