UniProtKB/Swiss-Prot P51787: Variant p.Gly589Asp

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information Variant position:

589 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 Glycine (G) to Aspartate (D) at position 589 (G589D, p.Gly589Asp). 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 glycine (G) to medium size and acidic (D) 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 LQT1 and JLNS1; affects plasma membrane localization; strongly reduces potassium current; impairs binding to AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1). Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs120074190 [ dbSNP | Ensembl ]

Sequence information Variant position:

589 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

676 The length of the canonical sequence.
Location on the sequence:

KPSLFISVSEKSKDRGSNTI G ARLNRVEDKVTQLDQRLALI 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                         KPSLFISVSEKSKDRGSNTIGARLNRVEDKVTQLDQRLALI

Mouse                         KPSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVII

Rat                           KPSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVII

Pig                           RPALFISSSEKVKDRGSNTIGARLNRVEDKVTQLDQRLELI

Rabbit                        KPSLFVPISEKSKDRGSNSIGARLNRVEDKVTQLDQRLVLI

Xenopus laevis                KPSLFLSVSDKVKDKGINTIGSRLNRVEDKVTQMDHKLNLI

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	1 – 676	Potassium voltage-gated channel subfamily KQT member 1
Topological domain	349 – 676	Cytoplasmic
Region	588 – 616	Interaction with AKAP9
Region	589 – 620	C-terminal assembly domain
Coiled coil	585 – 621
Mutagenesis	589 – 589	G -> M. No effect.
Mutagenesis	590 – 590	A -> W. Reduced cell surface expression and strongly reduced potassium current.
Mutagenesis	593 – 593	N -> G. Reduced cell surface expression and moderately reduced potassium current.
Mutagenesis	602 – 602	L -> A. Does not interact with AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with I-609.
Mutagenesis	609 – 609	I -> A. Does not interact with AKAP9 and the kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with L-602.
Helix	588 – 609

Literature citations
Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.
Marx S.O.; Kurokawa J.; Reiken S.; Motoike H.; D'Armiento J.; Marks A.R.; Kass R.S.;
Science 295:496-499(2002)
Cited for: INTERACTION WITH AKAP9; PHOSPHORYLATION AT SER-27; CHARACTERIZATION OF VARIANT LQT1 ASP-589; MUTAGENESIS OF SER-27; LEU-602 AND ILE-609; The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction.
Wiener R.; Haitin Y.; Shamgar L.; Fernandez-Alonso M.C.; Martos A.; Chomsky-Hecht O.; Rivas G.; Attali B.; Hirsch J.A.;
J. Biol. Chem. 283:5815-5830(2008)
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 574-622; INTERACTION WITH CALM; SUBCELLULAR LOCATION; MUTAGENESIS OF GLY-589; ALA-590 AND ASN-593; CHARACTERIZATION OF VARIANT LQT1 ASP-589; TETRAMERIZATION; Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Kapplinger J.D.; Tester D.J.; Salisbury B.A.; Carr J.L.; Harris-Kerr C.; Pollevick G.D.; Wilde A.A.; Ackerman M.J.;
Heart Rhythm 6:1297-1303(2009)
Cited for: VARIANTS LQT1 VAL-2; SER-7; THR-46; 64-PRO--PRO-70 DEL; PHE-66; THR-73; CYS-111; LEU-117; LEU-127; ILE-133; PRO-134; ALA-144; MET-153; MET-162; ARG-168; MET-172; CYS-174; HIS-174; THR-178; SER-179; HIS-184; ARG-186; GLN-190; LEU-190; TRP-195; VAL-198; ALA-199; MET-204; MET-215; MET-224; LEU-225; CYS-231; HIS-231; ASN-235; GLY-241; ASN-242; CYS-243; PRO-250; MET-254; CYS-259; LEU-259; VAL-262; PRO-266; SER-268; ASP-269; SER-269; ASP-272; PHE-273; VAL-274; LEU-277; PRO-277; GLU-280; CYS-281; PRO-282; GLY-283; ASP-292; CYS-293; GLU-302; VAL-302; PRO-303; ARG-305; SER-305; ARG-306; ILE-312; CYS-314; SER-314; CYS-315; VAL-316; SER-320; ALA-322; MET-322; ARG-325; TYR-339; GLU-341; GLY-341; VAL-341; PHE-342; LEU-343; ARG-350; SER-351; ARG-354; MET-360; ARG-362; HIS-365; GLN-366; TRP-366; HIS-374; GLY-379; LYS-385; PRO-389; THR-391 INS; TRP-397; ARG-398; GLU-446; LEU-448; TRP-451; SER-460; LEU-477; TRP-511; GLN-518; ARG-520; SER-522; GLY-524; THR-525; VAL-525; TRP-533; GLN-539; TRP-539; ILE-541; LYS-543; LEU-546; ARG-547; CYS-555; HIS-555; SER-555; GLU-557; PHE-566; PRO-566; TYR-566; THR-567; ARG-568; GLU-569; LEU-571; MET-587; ASP-589; CYS-591; HIS-591; GLN-594; PRO-594; GLU-596 DEL; LYS-596; MET-600; ASN-611; HIS-614 DEL; SER-626 AND ARG-635; 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)
Cited for: CHARACTERIZATION OF VARIANTS LQT1 LEU-546; CYS-555; HIS-555; GLU-557 AND ASP-589; INTERACTION WITH KCNE1 AND AKAP9; SUBCELLULAR LOCATION; FUNCTION; Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome.
Mousavi Nik A.; Gharaie S.; Jeong Kim H.;
Front. Cell. Neurosci. 9:32-32(2015)
Cited for: CHARACTERIZATION OF VARIANTS LQT1 ASN-242; PRO-243; HIS-250; VAL-306; ASN-317; ASP-586 AND MET-619; CHARACTERIZATION OF VARIANTS JLNS1 PHE-248; ILE-311; MET-322 AND ASP-589;

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.