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UniProtKB/Swiss-Prot P15382: Variant p.Pro127Thr

Potassium voltage-gated channel subfamily E member 1
Gene: KCNE1
Variant information

Variant position:  127
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 Proline (P) to Threonine (T) at position 127 (P127T, p.Pro127Thr).
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 medium size and hydrophobic (P) to medium size and polar (T)
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

Variant description:  In LQT5; moderately reduces I(KS) current density; no change of the voltage dependence of channel activation; markedly reduces interaction with KCNQ1 C-terminus; no effect on plasma membrane localization; loss of cAMP-mediated up-regulation of the I(KS) current; no effect on interaction with AKAP9; impairs phosphorylation at S-27 during cAMP-dependent stimulation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  127
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  129
The length of the canonical sequence.

Location on the sequence:   YVVENHLAIEQPNTHLPETK  P SP
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                         YVVENHLAIEQPNTHLPETKPSP

Mouse                         YVIENQAAVEQPATHLPELKPLS

Rat                           YVIENQAAVEQPATHLPELKPLS

Pig                           YAIENQAAVEQPATHLPELKPLS

Rabbit                        YVLENQLAVEHPDTHLPELKPSL

Cat                           YVIENQLAVERPNAHLPEIKPLS

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.

Chain 1 – 129 Potassium voltage-gated channel subfamily E member 1
Topological domain 67 – 129 Cytoplasmic
Region 109 – 129 interaction with KCNQ1 C-terminus
Mutagenesis 109 – 129 Missing. Totally suppressed interaction with KCNQ1 C-terminus.

Literature citations

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.
Splawski I.; Shen J.; Timothy K.W.; Lehmann M.H.; Priori S.G.; Robinson J.L.; Moss A.J.; Schwartz P.J.; Towbin J.A.; Vincent G.M.; Keating M.T.;
Circulation 102:1178-1185(2000)
Cited for: VARIANTS LQT5 HIS-32; TRP-98 AND THR-127;

Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP(2).
Dvir M.; Strulovich R.; Sachyani D.; Ben-Tal Cohen I.; Haitin Y.; Dessauer C.; Pongs O.; Kass R.; Hirsch J.A.; Attali B.;
J. Cell Sci. 127:3943-3955(2014)

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.