UniProtKB/SwissProt variant VAR

Variant information

Variant position:

690

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 Tryptophan (W) to Serine (S) at position 690 (W690S, p.Trp690Ser).

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 aromatic (W) to small size and polar (S)

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 XP-C; diminishes repair activity and impairs DNA binding.

Any additional useful information about the variant.

Sequence information

Variant position:

690

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

Protein sequence length:

940

The length of the canonical sequence.

Location on the sequence:

CRGEAVYSRDCVHTLHSRDT W LKKARVVRLGEVPYKMVKGF

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                         CRGEAVYSRDCVHTLHSRDTWLKKARVVRLGEVPYKMVKGF

Mouse                         CRGEAVYSRDCVHTLHSRDTWLKQARVVRLGEVPYKMVKGF

Drosophila                    IRGEAVYSRDCVHLLHSREIWLKSARVVKLGEQPYKVVKA-

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 – 940	DNA repair protein complementing XP-C cells
Region	496 – 734	Interaction with RAD23B
Region	607 – 766	Minimal sensor domain involved in damage recognition
Region	607 – 741	DNA-binding; preference for heteroduplex DNA
Alternative sequence	141 – 940	Missing. In isoform 3.

Literature citations

In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation.
Yasuda G.; Nishi R.; Watanabe E.; Mori T.; Iwai S.; Orioli D.; Stefanini M.; Hanaoka F.; Sugasawa K.;
Mol. Cell. Biol. 27:6606-6614(2007)
Cited for: CHARACTERIZATION OF VARIANT XP-C SER-690;

An aromatic sensor with aversion to damaged strands confers versatility to DNA repair.
Maillard O.; Solyom S.; Naegeli H.;
PLoS Biol. 5:E79-E79(2007)
Cited for: CHARACTERIZATION OF VARIANT XP-C SER-690; MUTAGENESIS OF PHE-733;

Two-stage dynamic DNA quality check by xeroderma pigmentosum group C protein.
Camenisch U.; Trautlein D.; Clement F.C.; Fei J.; Leitenstorfer A.; Ferrando-May E.; Naegeli H.;
EMBO J. 28:2387-2399(2009)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT OF VARIANT XP-C SER-690; MUTAGENESIS OF TRP-531; TRP-542; PHE-733 AND GLU-755;

Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels.
Chavanne F.; Broughton B.C.; Pietra D.; Nardo T.; Browitt A.; Lehmann A.R.; Stefanini M.;
Cancer Res. 60:1974-1982(2000)
Cited for: VARIANT XP-C SER-690;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q01831: Variant p.Trp690Ser