Channelpedia

KChip2a

Description: Kv channel-interacting protein 2
Gene: Kcnip2     Synonyms: Kchip2, kcnip2, KChIP2a, KChIP2b

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Introduction

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


Experimental data


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Gene

RGD ID Chromosome Position Species
70887 1 251008676-251032402 Rat
737095 19 45868160-45890293 Mouse
734096 10 103585731-103603677 Human

Kcnip2 : Kv channel-interacting protein 2


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Transcript

Acc No Sequence Length Source
NM_001033961 n/A n/A NCBI
NM_020094 n/A n/A NCBI
NM_020095 n/A n/A NCBI
NM_145704 n/A n/A NCBI
NM_030716 n/A n/A NCBI
NM_145703 n/A n/A NCBI
NM_173195 n/A n/A NCBI
NM_173192 n/A n/A NCBI
NM_014591 n/A n/A NCBI
NM_173191 n/A n/A NCBI
NM_173194 n/A n/A NCBI
NM_173197 n/A n/A NCBI
NM_173193 n/A n/A NCBI

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Ontology

Accession Name Definition Evidence
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. IEA
GO:0008076 voltage-gated potassium channel complex A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. IDA
GO:0030425 dendrite A neuron projection that has a short, tapering, often branched, morphology, receives and integrates signals from other neurons or from sensory stimuli, and conducts a nerve impulse towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. IDA

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Interaction

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])


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Protein


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Structure


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Distribution

KChIP2 expression in the t-tubules and the nucleus of heart muscle cells (in human and canine left ventricle) (Deschenes [128])


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Expression

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])


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Functional

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])


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Kinetics

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])


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Model


References

129

Patel SP. et al. Regulation of Kv4.3 voltage-dependent gating kinetics by KChIP2 isoforms.
J. Physiol. (Lond.), 2004 May 15 , 557 (19-41).

1195

Trimmer JS. et al. Modulation of A-type potassium channels by a family of calcium sensors.
Nature, 2000 Feb 3 , 403 (553-6).

1200

Rhodes KJ. et al. Role of heteromultimers in the generation of myocardial transient outward K+ currents.
Circ. Res., 2002 Mar 22 , 90 (586-93).

1201

Morales MJ. et al. Heterogeneous expression of KChIP2 isoforms in the ferret heart.
J. Physiol. (Lond.), 2002 Mar 15 , 539 (649-56).

1203

1204

Ozgen N. et al. Determinants of CREB degradation and KChIP2 gene transcription in cardiac memory.
Heart Rhythm, 2010 Jul , 7 (964-70).

1205


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Credits