K+ voltage-gated channel subfamily KQT member 2; KQT-like 2; neuroblastoma-specific K+ channel subunit alpha KvLQT2; voltage-gated K+ channel subunit Kv7.2 (KCNQ2)

Function

• role in regulation of neuronal excitability (putative)
• associates with KCNQ3 to form a K+ channel with essentially identical properties to the channel underlying the native M-current, a slowly activating & deactivating K+ conductance which plays a role in determining the subthreshold electrical excitability of neurons as well as responsiveness to synaptic inputs
• KCNQ2/KCNQ3 current is blocked by linopirdine & XE991, & activated by the anticonvulsant retigabine
• muscarinic agonist oxotremorine-M strongly suppresses KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors
• in Xenopus oocytes KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminus region
• heteromultimer with KCNQ3
• may associate with KCNE2

Structure

• the segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every third position (putative)
• belongs to the K+ channel family, KQT (TC 1.A.1.15) subfamily, Kv7.2/KCNQ2 sub-subfamily

Compartment

membrane

Alternative splicing

• named isoforms=6
• additional isoforms seem to exist
• at least one isoform may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

Expression

• expressed in adult & fetal brain
• highly expressed in areas containing neuronal cell bodies
• low levels of expression in spinal cord & corpus callosum
• isoform 2 is preferentially expressed in differentiated neurons
• isoform 6 is prominent in fetal brain, undifferentiated neuroblastoma cells & brain tumors

Pathology

• defects in KCNQ2 are the cause of benign fammilial neonatal epilepsy type 1

Notes

• inclusion of isoform 6 in heteromultimers results in attenuation of K+ current
• prominent expression of isoform 6 in the developing brain may alter firing repertoires of immature neurons to provide cues for proliferation rather than differentiation
• mutagenesis experiments were carried out in Xenopus oocytes by coexpression of either KCNQ2(mut) & KCNQ3 at the ratio of 1:1, or of KCNQ2(mut), KCNQ2(wt) & KCNQ3 at the ratio of 1:1:2, to mimic the situation in a heterozygous patient with benign familial neonatal epilepsy type 1

More general terms

• transmembrane 6 protein
• K+ channel subfamily KQT
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3785
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3785
• OMIM: https://mirror.omim.org/entry/121200
• OMIM: https://mirror.omim.org/entry/602235
• UniProt: http://www.uniprot.org/uniprot/O43526.html