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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P51787: Variant p.Ala590Thr

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information Variant position: help 590
Type of variant: help LP/P [Disclaimer]
Residue change: help From Alanine (A) to Threonine (T) at position 590 (A590T, p.Ala590Thr).
Physico-chemical properties: help Change from small size and hydrophobic (A) to medium size and polar (T)
BLOSUM score: help 0
Variant description: help In LQT1; reduces IKs density and causes a right-shift of the current?voltage relation of channel activation; reduces cell surface expression; no effect on interaction with AKAP9; does not affect the cAMP-dependent IKs up-regulation.
Other resources: help


Sequence information Variant position: help 590
Protein sequence length: help 676
Location on the sequence: help PSLFISVSEKSKDRGSNTIG A RLNRVEDKVTQLDQRLALIT
Residue conservation: help 
Human                         PSLFISVSEKSKDRGSNTIGARLNRVEDKVTQLDQRLALIT

Mouse                         PSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVIIT

Rat                           PSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVIIT

Pig                           PALFISSSEKVKDRGSNTIGARLNRVEDKVTQLDQRLELIT

Rabbit                        PSLFVPISEKSKDRGSNSIGARLNRVEDKVTQLDQRLVLIA

Xenopus laevis                PSLFLSVSDKVKDKGINTIGSRLNRVEDKVTQMDHKLNLIT
Sequence annotation in neighborhood: help
TypePositionsDescription
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 (tetramerization)
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
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
Tester D.J.; Will M.L.; Haglund C.M.; Ackerman M.J.;
Heart Rhythm 2:507-517(2005)
Cited for: VARIANTS LQT1 71-ALA--PRO-73 DEL; THR-73; GLY-115; TYR-122; ILE-133; PHE-136; LYS-160; ARG-168; CYS-174; GLN-190; PHE-204; LEU-225; ASN-235; ASN-242; CYS-243; MET-254; 254-VAL--PHE-256 DEL; CYS-259; LEU-259; ASP-261; PRO-266; SER-269; ASP-269; PHE-273; ARG-273; SER-276 DEL; LEU-277; HIS-278; LYS-290; ASP-292; CYS-293; VAL-302; ARG-304; SER-305; ILE-312; SER-314; ARG-314; ASP-314; CYS-315; ARG-316; ALA-322; PHE-339 DEL; VAL-341; SER-343; GLU-344; VAL-344; GLU-345; TRP-349; PRO-353; ARG-362; TRP-366; HIS-374; SER-380; TYR-389; TRP-452; GLY-524; GLU-526; TRP-539; LEU-546; CYS-555; HIS-555; TYR-566; SER-567; ARG-568; MET-587; THR-590; HIS-591; GLN-594; MET-619 AND SER-626; A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction.
Kinoshita K.; Komatsu T.; Nishide K.; Hata Y.; Hisajima N.; Takahashi H.; Kimoto K.; Aonuma K.; Tsushima E.; Tabata T.; Yoshida T.; Mori H.; Nishida K.; Yamaguchi Y.; Ichida F.; Fukurotani K.; Inoue H.; Nishida N.;
J. Mol. Cell. Cardiol. 72:273-280(2014)
Cited for: VARIANT LQT1 THR-590; CHARACTERIZATION OF VARIANT LQT1 THR-590;
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.