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UniProtKB/Swiss-Prot Q9UQ84: Variant p.Pro640Ser

Exonuclease 1
Gene: EXO1
Variant information

Variant position:  640
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Serine (S) at position 640 (P640S, p.Pro640Ser).
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 hydrophobic (P) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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

Polymorphism:  Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non-polyposis colorectal cancer (HNPCC) (PubMed:12517792). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors (PubMed:14623461).
Additional information on the polymorphism described.

Variant description:  Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770.
Any additional useful information about the variant.

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



Sequence information

Variant position:  640
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  846
The length of the canonical sequence.

Location on the sequence:   RTPSPSPSTALQQFRRKSDS  P TSLPENNMSDVSQLKSEESS
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                         RT---------------PSPSPSTALQQFRRKSDSPTSLPENNM---SDVSQLKSEESS

Mouse                         RT---------------PSPSASTTLQQFRRKSDPPACLPE

Xenopus laevis                SS---------------PTPKQSPMLLSLQKFHRTTPYMQN

Zebrafish                     KSVSHPARDSTERQRSSSTPSGLSTLQQFHRNKARISWAGP

Drosophila                    DK---------------GVPSPLESQEDLNNSQPQIPTEGN

Slime mold                    RNSGFSGFLKRKSSSQTAAPTTPTTPTTPKTSSSSSSTLTN

Baker's yeast                 -----------------------KVLQKFRYSSSFSGVNAN

Fission yeast                 ------------------------SYQTPNSASPPFSSLSH

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 1 – 846 Exonuclease 1
Region 600 – 846 Interaction with MSH2
Modified residue 621 – 621 Phosphothreonine
Modified residue 623 – 623 Phosphoserine
Modified residue 639 – 639 Phosphoserine
Modified residue 660 – 660 Phosphoserine
Mutagenesis 621 – 621 T -> A. No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-714.


Literature citations

Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome.
Sun X.; Zheng L.; Shen B.;
Cancer Res. 62:6026-6030(2002)
Cited for: FUNCTION; INTERACTION WITH MLH1 AND MSH2; CHARACTERIZATION OF VARIANTS LYS-109; ARG-410; SER-640; GLU-759 AND LEU-770;

Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms.
Wu Y.; Berends M.J.W.; Post J.G.; Mensink R.G.J.; Verlind E.; van der Sluis T.; Kempinga C.; Sijmons R.H.; van der Zee A.G.J.; Hollema H.; Kleibeuker J.H.; Buys C.H.C.M.; Hofstra R.M.W.;
Gastroenterology 120:1580-1587(2001)
Cited for: VARIANTS ALA-27; LYS-109; ARG-410; GLY-610; ALA-640; SER-640; GLU-759 AND LEU-770;

EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer.
Jagmohan-Changur S.; Poikonen T.; Vilkki S.; Launonen V.; Wikman F.; Orntoft T.F.; Moeller P.; Vasen H.; Tops C.; Kolodner R.D.; Mecklin J.-P.; Jaervinen H.; Bevan S.; Houlston R.S.; Aaltonen L.A.; Fodde R.; Wijnen J.; Karhu A.;
Cancer Res. 63:154-158(2003)
Cited for: VARIANTS SER-137; ARG-410; CYS-438; GLY-610; ALA-640; SER-640; GLU-759 AND VAL-827;

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.