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UniProtKB/Swiss-Prot Q92466: Variant p.Lys244Glu

DNA damage-binding protein 2
Gene: DDB2
Variant information

Variant position:  244
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Lysine (K) to Glutamate (E) at position 244 (K244E, p.Lys244Glu).
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 (K) to medium size and acidic (E)
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

Involvement in disease:  Xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-E patients show a mild phenotype with minimal or no neurologic features. {ECO:0000269|PubMed:8798680}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In XP-E; impairs DNA-binding of the UV-DDB complex.
Any additional useful information about the variant.

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



Sequence information

Variant position:  244
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  427
The length of the canonical sequence.

Location on the sequence:   NVILLNMDGKELWNLRMHKK  K VTHVALNPCCDWFLATASVD
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                         NVILLNMDGKELWNLRMHKKKVTHVALNPCCDWFLATASVD

Mouse                         HVILLSTDGKELWNLRMHKKKVAHVALNPCCDWLLATASID

Bovine                        HVILLNMDGRELWNLRMHKKKVTHVALNPCCDWLLATASVD

Chicken                       NVVLLSTSGEEIWKLKLHKKKVTHVEFNSRCEWLLATASVD

Xenopus tropicalis            NVVLLETCGKEIWKLRLHKKKVTHVEFNPRCDWLLASASVD

Zebrafish                     RLLLLGLDGHEIFKEKLHKAKVTHAEFNPRCDWLMATSSVD

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 – 427 DNA damage-binding protein 2
Repeat 244 – 287 WD 4
Alternative sequence 153 – 341 Missing. In isoform D1.
Alternative sequence 157 – 427 Missing. In isoform D2.
Alternative sequence 236 – 244 WNLRMHKKK -> VSVPMEPGS. In isoform D4.
Mutagenesis 258 – 258 L -> A. Impairs interaction with DDB1.
Mutagenesis 262 – 262 S -> A. Impairs interaction with DDB1.
Mutagenesis 264 – 264 D -> A. Impairs interaction with DDB1.


Literature citations

p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma pigmentosum group E cells that lack binding activity.
Hwang B.J.; Toering S.; Francke U.; Chu G.;
Mol. Cell. Biol. 18:4391-4399(1998)
Cited for: INTERACTION WITH DDB1; DNA-BINDING; CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273;

Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation.
Nichols A.F.; Itoh T.; Graham J.A.; Liu W.; Yamaizumi M.; Linn S.;
J. Biol. Chem. 275:21422-21428(2000)
Cited for: DNA-BINDING; SUBCELLULAR LOCATION; INDUCTION; CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273;

DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.
Wittschieben B.O.; Iwai S.; Wood R.D.;
J. Biol. Chem. 280:39982-39989(2005)
Cited for: INTERACTION WITH DDB1; DNA-BINDING; CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273;

Mutations specific to the xeroderma pigmentosum group E Ddb-phenotype.
Nichols A.F.; Ong P.; Linn S.;
J. Biol. Chem. 271:24317-24320(1996)
Cited for: VARIANTS XP-E GLU-244 AND HIS-273;

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.