UniProtKB/SwissProt variant VAR

Variant information

Variant position:

85

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

Type of variant:

Unclassified

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 Proline (P) to Leucine (L) at position 85 (P85L, p.Pro85Leu).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The gene represented in this entry may be involved in disease pathogenesis.

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 an osteogenic sarcoma sample; neutral allele among Ashkenazi Jewish women.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs17883862 [ dbSNP | Ensembl ]

Sequence information

Variant position:

85

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:

TVSTQELYSIPEDQEPEDQE P EEPTPAPWARLWALQDGFAN

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                         TVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFAN

Mouse                         TVSTQELCSIPED-----QEPEEPGPAPWARLWALQDGFSN

Caenorhabditis elegans        ---------MPVDEDLVVGESQCAASKPFAKLVGVRRGISS

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
Modified residue	68 – 68	Phosphothreonine; by ATM and MAP3K20
Modified residue	73 – 73	Phosphoserine; by PLK3
Alternative sequence	1 – 221	Missing. In isoform 13.
Alternative sequence	75 – 392	Missing. In isoform 11.
Mutagenesis	68 – 68	T -> A. Loss of activation and phosphorylation.
Mutagenesis	73 – 73	S -> A. Impaired activation, phosphorylation by ATM and G2/M transition checkpoint.

Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-85; THR-157; MET-436; LYS-446; ILE-447; SER-448; LYS-501 AND VAL-512;

Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors.
Miller C.W.; Ikezoe T.; Krug U.; Hofmann W.K.; Tavor S.; Vegesna V.; Tsukasaki K.; Takeuchi S.; Koeffler H.P.;
Genes Chromosomes Cancer 33:17-21(2002)
Cited for: VARIANTS OSTEOSARCOMA SER-17 AND LEU-85;

Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.
Shaag A.; Walsh T.; Renbaum P.; Kirchhoff T.; Nafa K.; Shiovitz S.; Mandell J.B.; Welcsh P.; Lee M.K.; Ellis N.; Offit K.; Levy-Lahad E.; King M.-C.;
Hum. Mol. Genet. 14:555-563(2005)
Cited for: VARIANTS LEU-85 AND PHE-428;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O96017: Variant p.Pro85Leu