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UniProtKB/Swiss-Prot Q9UQ84: Variant p.Arg723Cys

Exonuclease 1
Gene: EXO1
Variant information

Variant position:  723
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 Arginine (R) to Cysteine (C) at position 723 (R723C, p.Arg723Cys).
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 large size and basic (R) to medium size and polar (C)
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

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.

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



Sequence information

Variant position:  723
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:   EESDCNIKLLDSQSDQTSKL  R LSHFSKKDTPLRNKVPGLYK
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                         EESDCNIKLLDSQSDQTSKLRLSHFSKKDTPL-RNKVPGLYK

Mouse                         EESDCNNKSLDNQGEQNSKQHLPHFSK-KDGLRRNKVPGLC

Xenopus laevis                DEHASTPESPCQFTMKASPAHQSFFPEPKGSAPKSKVPGLL

Zebrafish                     VTEDNSDKEKERDSVVSNSPSSSPLDRLKPAVNRTKVSGLS

Drosophila                    --DSCSSDQRASSTSSSSQQRQNFLPTSKRRV------GLS

Slime mold                    NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNDNNN

Baker's yeast                 RDDDCDDNDGKNQITQRPSLRKSLIGARSQRI---------

Fission yeast                 --------------GHDALNRKNHASLPSRRI-------VY

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 714 – 714 Phosphoserine; by ATR
Mutagenesis 714 – 714 S -> A. No rescue of HU-induced degradation and loss of HU-induced increase of phosphorylation. No rescue of HU-induced degradation; when associated with A-621. No rescue of HU-induced degradation; when associated with A-454. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-621.


Literature citations

Human exonuclease I interacts with the mismatch repair protein hMSH2.
Schmutte C.; Marinescu R.C.; Sadoff M.M.; Guerrette S.; Overhauser J.; Fishel R.;
Cancer Res. 58:4537-4542(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); INTERACTION WITH MSH2; TISSUE SPECIFICITY; VARIANTS ARG-354; LYS-589; GLY-670; CYS-723 AND LEU-757;

Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination.
Tishkoff D.X.; Amin N.S.; Viars C.S.; Arden K.C.; Kolodner R.D.;
Cancer Res. 58:5027-5031(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]; ALTERNATIVE SPLICING; TISSUE SPECIFICITY; VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723;

Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1.
Wilson D.M. III; Carney J.P.; Coleman M.A.; Adamson A.W.; Christensen M.; Lamerdin J.E.;
Nucleic Acids Res. 26:3762-3768(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]; ALTERNATIVE SPLICING; FUNCTION; TISSUE SPECIFICITY; VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723;

Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance.
Qiu J.; Qian Y.; Chen V.; Guan M.-X.; Shen B.;
J. Biol. Chem. 274:17893-17900(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); PROTEIN SEQUENCE OF 1-7 (ISOFORMS 1/2); FUNCTION; VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ILE-76; GLY-93; SER-279; SER-299; ARG-354; ASN-428; MET-439; TYR-456; MET-458; LEU-460; THR-503; LYS-589; GLN-634; GLY-670; CYS-723; LEU-757 AND GLU-759;

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANTS GLY-670 AND CYS-723;

The full-ORF clone resource of the German cDNA consortium.
Bechtel S.; Rosenfelder H.; Duda A.; Schmidt C.P.; Ernst U.; Wellenreuther R.; Mehrle A.; Schuster C.; Bahr A.; Bloecker H.; Heubner D.; Hoerlein A.; Michel G.; Wedler H.; Koehrer K.; Ottenwaelder B.; Poustka A.; Wiemann S.; Schupp I.;
BMC Genomics 8:399-399(2007)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-846 (ISOFORM 1); VARIANTS LYS-589; GLY-670 AND CYS-723;

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.