KChIP2
Description: Kv channel-interacting protein 2 Gene: kcnip2 Alias: Kchip2, kcnip2, KChIP2a, KChIP2b
Compelling evidence from transgenic mice, immunoprecipitation data, gene expression analyses and functional heterologous expression studies supports the role of Kv channel interacting proteins (KChIPs) as modulators of Kv4 channels underlying the cardiac transient outward current and neuronal A-type current (An et al. 2000 [1195]; Rosati et al. 2001 [1198]; Kuo et al. 2001 [1197]; Bähring et al. 2001 [1199]; Guo et al. 2002a [1200]; Patel et al. 2002 [1201]. KChIPs are calcium-binding proteins with four EF-hands that slow inactivation kinetics and accelerate recovery kinetics of Kv4 channels. (Patel [127])
Kcnip2 (also known as KCHIP2; MGC17241; DKFZp566L1246) encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene.
http://www.ncbi.nlm.nih.gov/gene/30819
Gene
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_014591.5 | 2469 | |
| Mouse | NM_145703.2 | 2414 | |
| Rat | NM_020094.2 | 2370 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Structure
KChIP2 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
The predominant effects of all 3 KChIP2 splice variants on hKv4.3-encoded current are to increase the density, slow the current decay in a Ca2+-dependent manner, and hasten recovery from inactivation in a splice variant–specific fashion. (Deschenes [128])
KChIP2 is the only member of the KChIP family expressed in the heart. (Deschênes [128])
KChIP2, KChIP3, and KChIP4 are robustly expressed in adult mouse posterior (visual) cortex and all three proteins coimmunoprecipitate with Kv4.2. (Norris [1202])
KChIP2 expression in the t-tubules and the nucleus of heart muscle cells (in human and canine left ventricle) (Deschenes [128])
The functional effects of all of the KChIP2 splice variants on hKv4.3 current decay expressed in mammalian cells diminish rather than enhance the mimicry of cardiac Ito current. Although mouse KChIP2 was shown to be necessary for expression of Ito in mouse heart (Kuo [1199], other data cast doubt on the notion that KChIP2 alone is responsible for the density gradient and biophysical features of native human and canine cardiac Ito. (Deschênes [128])
NS5806 modulated K(V)4 channel gating depending on the presence of KChIP2, suggesting that NS5806 can potentially be used to address the molecular composition as well as the physiological role of cardiac I(to). ( Lundby [1203])
References
Elucidating KChIP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChIP2 isoform.
J. Physiol. (Lond.), 2002 Nov 15 , 545 (5-11).
Deschênes I
et al.
Regulation of Kv4.3 current by KChIP2 splice variants: a component of native cardiac I(to)?
Circulation,
2002
Jul
23
, 106 (423-9).
Patel SP
et al.
Regulation of Kv4.3 voltage-dependent gating kinetics by KChIP2 isoforms.
J. Physiol. (Lond.),
2004
May
15
, 557 (19-41).
An WF
et al.
Modulation of A-type potassium channels by a family of calcium sensors.
Nature,
2000
Feb
3
, 403 (553-6).
Bähring R
et al.
Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.
J. Biol. Chem.,
2001
Jun
29
, 276 (23888-94).
Rosati B
et al.
Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle.
J. Physiol. (Lond.),
2001
May
15
, 533 (119-25).
Kuo HC
et al.
A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.
Cell,
2001
Dec
14
, 107 (801-13).
Guo W
et al.
Role of heteromultimers in the generation of myocardial transient outward K+ currents.
Circ. Res.,
2002
Mar
22
, 90 (586-93).
Patel SP
et al.
Heterogeneous expression of KChIP2 isoforms in the ferret heart.
J. Physiol. (Lond.),
2002
Mar
15
, 539 (649-56).
Norris AJ
et al.
Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in the generation of Kv4-encoded IA channels in cortical pyramidal neurons.
J. Neurosci.,
2010
Oct
13
, 30 (13644-55).
Lundby A
et al.
Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2.
Br. J. Pharmacol.,
2010
Aug
, 160 (2028-44).
Ozgen N
et al.
Determinants of CREB degradation and KChIP2 gene transcription in cardiac memory.
Heart Rhythm,
2010
Jul
, 7 (964-70).
Jin H
et al.
KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling.
J. Mol. Cell. Cardiol.,
2010
Jun
, 48 (1169-79).
Credits
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