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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41181: Variant p.Pro262Leu

Aquaporin-2
Gene: AQP2
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Variant information Variant position: help 262 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 Proline (P) to Leucine (L) at position 262 (P262L, p.Pro262Leu). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In NDI2; mutant protein folds properly and is functional but is retained in intracellular vesicles; able to assemble into tetramers with wild-type AQP2 that properly localize to the apical membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 262 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 PDTDWEEREVRRRQSVELHS P QSLPRGTKA 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                         PDTDWEEREVRRRQSVELHSPQSLPRGTKA

Mouse                         PDTDWEEREVRRRQSVELHSPQSLPRGSKA

Rat                           PDTDWEEREVRRRQSVELHSPQSLPRGSKA

Bovine                        PDTDWEEREVRRRQSVELHSPQSLPRGSKA

Sheep                         PDTDWEEREVRRRQSVELHSPQSLPRGTKA
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
Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus.
Kuwahara M.;
Intern. Med. 37:215-217(1998)
Cited for: VARIANTS NDI2 MET-125; ARG-175; THR-190 AND LEU-262; A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.
de Mattia F.; Savelkoul P.J.M.; Bichet D.G.; Kamsteeg E.-J.; Konings I.B.M.; Marr N.; Arthus M.-F.; Lonergan M.; van Os C.H.; van der Sluijs P.; Robertson G.; Deen P.M.T.;
Hum. Mol. Genet. 13:3045-3056(2004)
Cited for: VARIANTS NDI2 CYS-187; THR-190 AND LEU-262; CHARACTERIZATION OF VARIANTS NDI2 CYS-187; THR-190 AND LEU-262; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; MUTAGENESIS OF PRO-262;
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.