Recombinant Human Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) Protein

Function

Non-functional alone but modulatory when coexpressed with the full-length isoform 1

Subcellular Location

Cell membrane (Multi-pass membrane protein); Cytoplasmic vesicle membrane; Early endosome; Membrane raft; Endoplasmic reticulum; Basolateral cell membrane; Apical cell membrane (Multi-pass membrane protein)

Disease Association

Long QT syndrome 1 (LQT1) : A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. [The disease is caused by variants affecting the gene represented in this entry] | Jervell and Lange-Nielsen syndrome 1 (JLNS1) : An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. [The disease is caused by variants affecting the gene represented in this entry] | Atrial fibrillation, familial, 3 (ATFB3) : An autosomal dominant form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. [The disease is caused by variants affecting the gene represented in this entry] | Short QT syndrome 2 (SQT2) : An autosomal dominant form of short QT syndrome, a heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It can cause syncope and sudden death. [The disease is caused by variants affecting the gene represented in this entry] | Type 2 diabetes mellitus (T2D) : A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. [Disease susceptibility is associated with variants affecting the gene represented in this entry]

Tissue Specificity

Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries

Subunit

Tetramer (PubMed:18165683, PubMed:19693805, PubMed:25441029, PubMed:31883792). Heterotetramer with KCNE1; targets to the membrane raft (PubMed:19693805, PubMed:20533308, PubMed:25037568). Interacts (via C-terminus) with calmodulin; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry); the interaction is calcium-independent, constitutive, participates in the proper assembly of a functional channel and also acts a calcium sensor (PubMed:16556865, PubMed:18165683, PubMed:25441029, PubMed:31883792). KCNQ1 channels interact more strongly with Ca(2+)-CALM than with apoCALM (PubMed:16556865). Interacts with AKAP9; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1 complex, allowing PKA-mediated phosphorylation and increase of delayed rectifier potassium channel activity (PubMed:11799244, PubMed:25037568). Interacts with KCNE2; forms a heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505, PubMed:20533308). Interacts with AP2M1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with NEDD4L; promotes internalization and decreases I(Ks) currents (PubMed:22024150, PubMed:23529131). Interacts with USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization (PubMed:22024150). Heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Interacts with KCNE3; four KCNE3 molecules are bound to one KCNQ1 tetramer (4:4 KCNQ1:KCNE3 stoichiometry); alters membrane raft localization; affects KCNQ1 structure and gating properties (PubMed:20533308, PubMed:31883792). Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity (PubMed:19687231, PubMed:20533308). Interacts with KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization (PubMed:12324418, PubMed:20533308). Interacts with SLC5A3; forms coregulatory channel-transporter complexes that modulate Na(+)-coupled myo-inositol influx through the transporter (By similarity)

• Chouabe C. et al. Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. — EMBO J. (1997)
• Jiang M. et al. Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart. — J. Biol. Chem. (1997)
• Itoh T. et al. Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome. — Hum. Genet. (1998)
• Neyroud N. et al. Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. — Circ. Res. (1999)
• Seebohm G. et al. PubMed: CI-DNU07QDNT8R0O (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)