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Kv12.3

potassium voltage-gated channel, subfamily H (eag-related), member 4
Synonyms: Kv12.3. Symbol: Kcnh4

Introductions

KCNH4 encodes Kv12.3 (also known as BEC2; ELK1), a pore-forming (alpha) subunit. The gene is brain-specific, and located in the neocortex and the striatum. It may be involved in cellular excitability of restricted neurons in the central nervous system.

http://www.ncbi.nlm.nih.gov/gene/23415

Genes

See figure 2 in Gutman [606] for a phylogenetic tree.

Kcnh4 : potassium voltage-gated channel, subfamily H (eag-related), member 4

RGD ID	Chromosome	Position	Species
621415	10	89677981-89697799	Rat
1607166		-	Mouse
733889	17	40308910-40333296	Human

Transcripts

Acc No	Sequence	Length	Source
NM_053630			NCBI
NM_012285			NCBI

Ontologies

Accession	Name	Definition	Evidence
GO:0016021	integral to membrane	Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.	IEA
GO:0016020	membrane	Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.	IEA

Interactions

Ba2+

Ba2+ blocks Kv12.3. [809]

KCNH8

Coexpression of KCNH8 with dominant-negative KCNH8, KCNH3, and KCNH4 subunits led to suppression of the KCNH8 currents, suggesting that Elk channels can form heteromultimers. [808]

pH

Kv10.2, Kv12.2, and Kv12.3 are similarly modulated by external pH. Thus high pH sensitivity has now been observed for six of eight mammalian EAG superfamily orthologues, including all members of the Eag and Elk gene families. The Erg family channels Kv11.2 and Kv11.3 have not yet been examined for pH sensitivity, but they also have the EAG-specific acidic residues [1832]

Tau protein and KCNH4 mRNA levels

Overexpression of tau protein lead to the reduction of KCNH4 mRNA levels in mouse neuroplastoma cells [2087]and human neuroplastoma cells [2088]

Proteins

Structures

There are light oxygen voltage (LOV) and cyclic nucleotide binding (CNB) domains in the N and C terminus, respectively. [606]

Distributions

Expressions

Brain (telencephalon),[809], [810] neuroblastoma, esophagus, oligodendroglioma, lung, primary B-cell neoplasia, cerebellum, pituitary gland [795].

Functionals

Kinetics

Kv12.3 is a slowly activating voltage-gated potassium channel with threshold for activation at 90 mV [809].

Models

References

[604 : 20628086]	Bailey SD. et al. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. Diabetes Care, 2010 Oct , 33 (2250-3).
[606 : 16382104]	Gutman GA. et al. International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol. Rev., 2005 Dec , 57 (473-508).
[810 : 10455180]	Miyake A. et al. New ether-à-go-go K(+) channel family members localized in human telencephalon. J. Biol. Chem., 1999 Aug 27 , 274 (25018-25).
[808 : 12890647]	Zou A. et al. Distribution and functional properties of human KCNH8 (Elk1) potassium channels. Am. J. Physiol., Cell Physiol., 2003 Dec , 285 (C1356-66).
[809 : 9824707]	Engeland B. et al. Cloning and functional expression of rat ether-à-go-go-like K+ channel genes. J. Physiol. (Lond.), 1998 Dec 15 , 513 ( Pt 3) (647-54).
[327 : 11425889]	Saganich MJ. et al. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. J. Neurosci., 2001 Jul 1 , 21 (4609-24).
[795 : 10718922]	Wulfsen I. et al. Expression of mRNA for voltage-dependent and inward-rectifying K channels in GH3/B6 cells and rat pituitary. J. Neuroendocrinol., 2000 Mar , 12 (263-72).
[1760 : 24719561]	Heo SH. et al. ELK3 suppresses angiogenesis by inhibiting the transcriptional activity of ETS-1 on MT1-MMP. Int. J. Biol. Sci., 2014 , 10 (438-47).
[1761 : 24680769]	Chan JK. et al. MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecol. Oncol., 2014 Jun , 133 (568-74).
[1832 : 23712551]	Kazmierczak M. et al. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor. J. Gen. Physiol., 2013 Jun , 141 (721-35).
[2087 : 25590133]	Li X. et al. Overexpression of tau downregulated the mRNA levels of Kv channels and improved proliferation in N2A cells. PLoS ONE, 2015 , 10 (e0116628).
[2088 : 26576773]	Hu XM. et al. The Tau-Induced Reduction of mRNA Levels of Kv Channels in Human Neuroblastoma SK-N-SH Cells. J. Mol. Neurosci., 2016 Feb , 58 (306-11).