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UniProtKB/Swiss-Prot P40692: Variant p.Leu574Pro

DNA mismatch repair protein Mlh1
Gene: MLH1
Variant information

Variant position:  574
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Leucine (L) to Proline (P) at position 574 (L574P, p.Leu574Pro).
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

Variant description:  In HNPCC2; type I; abrogates interaction with EXO1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  574
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:   KLSEELFYQILIYDFANFGV  L RLSEPAPLFDLAMLALDSPE
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                         KLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPE

Mouse                         KLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPE

Rat                           KLSEELFYQILIYDFANFGVLRLPEPAPLFDFAMLALDSPE

Slime mold                    NITKELFYQLSLLRFSDFDSIKFSQSLSIYSLLLVSLDSPL

Baker's yeast                 SVCYELFYQIGLTDFANFGKINLQSTNVSDDIVLYNLLSEF

Fission yeast                 KLSYHLFYQICLTEFGNYGEFVLETPLSISDLFEIV-----

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.

TypePositionsDescription
Chain 2 – 756 DNA mismatch repair protein Mlh1
Region 410 – 650 Interaction with EXO1
Beta strand 572 – 581


Literature citations

Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC).
Han H.-J.; Maruyama M.; Baba S.; Park J.-G.; Nakamura Y.;
Hum. Mol. Genet. 4:237-242(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HNPCC2 LEU-542; PRO-574; VAL-582 AND THR-618;

The interaction of DNA mismatch repair proteins with human exonuclease I.
Schmutte C.; Sadoff M.M.; Shim K.-S.; Acharya S.; Fishel R.;
J. Biol. Chem. 276:33011-33018(2001)
Cited for: INTERACTION WITH EXO1 AND PMS2; CHARACTERIZATION OF VARIANTS HNPCC2 PRO-574; LYS-616 DEL; LEU-659 AND THR-681; CHARACTERIZATION OF VARIANT MMRCS LYS-616 DEL;

Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer.
Han H.-J.; Yuan Y.; Ku J.-L.; Oh J.-H.; Won Y.-J.; Kang K.J.; Kim K.Y.; Kim S.; Kim C.Y.; Kim J.-P.; Oh N.-G.; Lee K.H.; Choe K.J.; Nakamura Y.; Park J.-G.;
J. Natl. Cancer Inst. 88:1317-1319(1996)
Cited for: VARIANTS HNPCC2 CYS-217; LEU-542; PRO-549 AND PRO-574;

Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families.
Shin Y.-K.; Heo S.-C.; Shin J.-H.; Hong S.-H.; Ku J.-L.; Yoo B.-C.; Kim I.-J.; Park J.-G.;
Hum. Mutat. 24:351-351(2004)
Cited for: VARIANTS HNPCC2 CYS-217; GLY-282; LEU-542; PRO-542; PRO-549; PRO-574; PRO-636; SER-640 AND MET-724;

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.