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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41181: Variant p.Glu258Lys

Aquaporin-2
Gene: AQP2
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Variant information Variant position: help 258 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glutamate (E) to Lysine (K) at position 258 (E258K, p.Glu258Lys). 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: help Change from medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In NDI2; retained in the Golgi compartment. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 258 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 271 The length of the canonical sequence.
Location on the sequence: help KGLEPDTDWEEREVRRRQSV E LHSPQSLPRGTKA 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA

Mouse                         KGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Rat                           KGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Bovine                        KGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Sheep                         KGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA
Sequence annotation in neighborhood: help 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 – 271 Aquaporin-2
Topological domain 223 – 271 Cytoplasmic
Region 248 – 271 Disordered
Modified residue 256 – 256 Phosphoserine; by PKA
Mutagenesis 244 – 244 T -> A. No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis.
Mutagenesis 244 – 244 T -> E. No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis.
Mutagenesis 256 – 256 S -> A. Retained in vesicles.
Mutagenesis 256 – 256 S -> D. Expressed in the apical membrane.
Mutagenesis 262 – 262 P -> A. No effect on expression at the apical cell membrane.



Literature citations
An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.
Mulders S.M.; Bichet D.G.; Rijss J.P.L.; Kamsteeg E.-J.; Arthus M.-F.; Lonergan M.; Fujiwara M.; Morgan K.; Leijendekker R.; van der Sluijs P.; van Os C.H.; Deen P.M.T.;
J. Clin. Invest. 102:57-66(1998)
Cited for: VARIANT NDI2 LYS-258; Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus.
Kamsteeg E.-J.; Stoffels M.; Tamma G.; Konings I.B.M.; Deen P.M.T.;
Hum. Mutat. 30:1387-1396(2009)
Cited for: MISSORTING MOTIF OF VARIANT NDI2 LYS-258;
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.