UniProtKB/Swiss-Prot P40692 : Variant p.Ala492Thr
DNA mismatch repair protein Mlh1
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Variant information
Variant position:
492
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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:
492 (A492T, p.Ala492Thr).
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:
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
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).following page
Variant description:
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
492
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
756
The length of the canonical sequence.
Location on the sequence:
A ACTPRRRIINLTSVLSLQEE
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 RHREDSDVEMVEDDSRK-EMTA ACTPRR----RI-INLTSVLSLQEE
Mouse RHREDSDVEMVENASGK-EMTA ACYPRR----RI-INLTSV
Rat RHPEDSDVEMMENDSRK-EMTA ACYPRR----RI-INLTSV
Slime mold TATTKSNSPASKNDIKKLQEHT FITPRKTRKYKQ-VELTSI
Baker's yeast ---EKNALPISKDGYIR----- --VPKE----RVNVNLTSI
Fission yeast DIKDLQTEEIVEEGNS------ -------------IDLESI
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 – 756 DNA mismatch repair protein Mlh1
Region
410 – 650 Interaction with EXO1
Modified residue
477 – 477 Phosphoserine
Mutagenesis
472 – 472 R -> N. Affects binding to importins alpha, including KPNA2, hence may affect import to the nucleus.
Literature citations
Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer.
Moslein G.; Tester D.J.; Lindor N.M.; Honchel R.; Cunningham J.M.; French A.J.; Halling K.C.; Schwab M.; Goretzki P.; Thibodeau S.N.;
Hum. Mol. Genet. 5:1245-1252(1996)
Cited for: VARIANTS LYNCH2 LYS-616 DEL AND THR-618; VARIANT CRC THR-492;
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.
