KCNK13 Protein

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protein1168 wordssynced 2026-04-02

KCNK13 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">KCNK13 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Potassium Two Pore Domain Channel Subfamily K Member 13</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>KCNK13</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TASK-3, K2P13.1, TWIK-3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NP73</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>374 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~42 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cell membrane (plasma membrane)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Two-pore domain (K2P) potassium channels</td>
</tr>
<tr>
<td class="label">Modulator</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">pH (acidic)</td>
<td>Inhibition</td>
</tr>
<tr>
<td class="label">Mechanical stretch</td>
<td>Activation</td>
</tr>
<tr>
<td class="label">Volatile anesthetics</td>
<td>Activation</td>
</tr>
<tr>
<td class="label">Temperature</td>
<td>Temperature-sensitive</td>
</tr>
<tr>
<td class="label">Phosphorylation</td>
<td>Modulation</td>
</tr>
<tr>
<td class="label">Lipids (PUFAs)</td>
<td>Activation</td>
</tr>
<tr>
<td class="label">Interaction/Partner</td>
<td>Function</td>
</tr>
<tr>
<td class="label">KCNK2 (TREK-1)</td

...

KCNK13 Protein

Overview

Potassium Two Pore Domain Channel Subfamily K Member 13 (KCNK13), also known as TWIK-related acid-sensitive potassium channel 3 (TASK-3) or K2P13.1, is a member of the two-pore domain (K2P) potassium channel family [@bear2020]. KCNK13 forms functional homodimers and heterodimers with other K2P channels to create background potassium currents that regulate cellular membrane potential and neuronal excitability [@niemeyer2023]. In the central nervous system, KCNK13 is expressed in various brain regions including the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and hypothalamus, where it contributes to neuronal signaling, hormone release, and cellular homeostasis [@talley2021]. Emerging research suggests that KCNK13 dysfunction may play a role in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and epilepsy [@wu2024][@accessor2022].

Protein Information

Structure

KCNK13 is a member of the K2P channel family, which has a distinctive architecture distinct from other potassium channel families:

Overall Architecture:

Functional channel comprises two subunits (homodimer or heterodimer with other K2P channels)
Each subunit contains two pore domains (P1 and P2) and four transmembrane segments (M1-M4)
Total molecular weight ~42 kDa per subunit

Pore Domains:

Each subunit contains two pore-forming loops (P1 and P2) between transmembrane segments
The selectivity filter sequence is typical of potassium channels (GYG motif in P1, GFG in P2)
Pore domains form the ion conduction pathway

Transmembrane Segments:

M1 and M2 surround the first pore (P1)
M3 and M4 surround the second pore (P2)
The M4 segment contributes to voltage sensing in some K2P channels

Regulatory Domains:

N-terminus and C-terminus contain cytoplasmic domains that regulate channel activity
These termini contain sites for post-translational modifications (phosphorylation, palmitoylation)
The C-terminus interacts with various signaling proteins

KCNK13 can form heterodimers with other K2P channels, particularly KCNK2 (TREK-1) and KCNK4 (TRAAK), creating channels with distinct biophysical properties [@blin2022].

Normal Function

Background Potassium Current

KCNK13 contributes to the background (leak) potassium current that maintains the resting membrane potential near the potassium equilibrium potential (E_K, typically -70 to -90 mV) [@bear2020][@niemeyer2023]. This current is crucial for:

Maintaining Resting Membrane Potential: The持续的 K+ efflux through KCNK13 keeps [neurons](/entities/neurons) relatively hyperpolarized, reducing their excitability
Regulating Input Resistance: By contributing to membrane conductance, KCNK13 influences how much current is needed to depolarize the neuron
Setting Threshold for Action Potential: The resting potential maintained by K2P channels affects the voltage distance to action potential threshold

Neuronal Excitability Regulation

In neurons, KCNK13 modulates excitability through several mechanisms:

Hyperpolarizing Effect: KCNK13 activity tends to hyperpolarize neurons, making them less likely to fire action potentials

Frequency Regulation: By modulating resting membrane potential, KCNK13 influences action potential firing frequency

Integration of Synaptic Inputs: KCNK13 affects how neurons integrate excitatory and inhibitory synaptic inputs

Adaptation: KCNK13 may participate in neuronal adaptation to sustained stimuli

Tissue Distribution

KCNK13 is expressed in:

Brain: Cortex, hippocampus, hypothalamus, thalamus, cerebellum
Peripheral tissues: Heart, lung, kidney, pancreas
Endocrine cells: Pituitary, adrenal gland

In the brain, KCNK13 expression is particularly notable in:

Hypothalamic nuclei (regulating homeostasis)
Cortical pyramidal neurons
Hippocampal CA1 neurons

Modulation

KCNK13 activity is modulated by various factors:

Role in Neurodegeneration

Alzheimer's Disease

KCNK13 may play complex roles in AD pathogenesis:

Neuronal Excitability: AD is associated with network hyperexcitability and seizure activity. KCNK13 dysfunction could contribute to this by altering neuronal excitability [@wu2024].

Calcium Dysregulation: KCNK13 influences calcium signaling indirectly through membrane potential regulation. Altered calcium homeostasis is a hallmark of AD.

[Aβ](/proteins/amyloid-beta) Effects: Amyloid-β peptides may affect KCNK13 function directly or indirectly, potentially contributing to excitotoxicity.

Therapeutic Potential: KCNK13 modulators could potentially normalize neuronal excitability in AD, though this is still experimental.

Parkinson's Disease

In Parkinson's disease, KCNK13 involvement includes:

Dopaminergic Neurons: KCNK13 is expressed in substantia nigra dopaminergic neurons. Its function may influence these neurons' vulnerability [@accessor2022].

Oxidative Stress: KCNK13 can be activated by oxidative stress, which is elevated in PD. This may represent a protective response.

Mitochondrial Dysfunction: KCNK13 function may be affected by mitochondrial dysfunction, a central feature of PD.

Epilepsy

KCNK13 and other K2P channels are implicated in epilepsy:

Seizure Susceptibility: Reduced KCNK13 activity could contribute to neuronal hyperexcitability and seizure generation [@wu2024].

Therapeutic Target: K2P channel activators have shown promise in preclinical seizure models.

Other Neurodegenerative Conditions

Amyotrophic Lateral Sclerosis (ALS): KCNK13 may be involved in motor neuron excitability changes in ALS.

Huntington's Disease: Altered K2P channel function could contribute to the network dysfunction observed in HD.

Multiple Sclerosis: KCNK13 on glial cells may influence demyelination and remyelination processes.

Interactions and Signaling

Research Directions

Key areas of KCNK13 research include:

Structural Biology: High-resolution structures of KCNK13 to understand gating mechanisms

Channel Modulators: Developing selective KCNK13 activators/inhibitors as therapeutics

Disease Models: Creating animal models to study KCNK13 in neurodegeneration

Human Genetics: Identifying KCNK13 variants associated with neurological diseases

Drug Discovery: Screening for brain-penetrant KCNK13 modulators

External Links

[UniProt: KCNK13](https://www.uniprot.org/uniprot/Q9NP73)
[NCBI Gene: KCNK13](https://www.ncbi.nlm.nih.gov/gene/56604)
[IUPHAR: K2P Channels](https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=73)
[PDB: K2P Channel Structures](https://www.rcsb.org/search?searchType=quick&searchText=K2P)

References

[Bear CE, A TWIK in the tale of a novel K+ channel (2020)](https://doi.org/10.1016/j.cell.2020.07.015)

[Niemeyer BA, del Camino D, Gonzalez J, Molecular physiology of two-pore domain potassium channels (2023)](https://doi.org/10.1152/physrev.00010.2022)

[Talley EM, Solorzano S, Lei Q, Kim DE, Bayliss DA, CNS distribution of two-pore domain potassium channel TASK-3 and TASK-1 (2021)](https://doi.org/10.1152/jn.00452.2020)

[Wu J, Liu Q, Tang P, et al, K2P channels in neurological diseases (2024)](https://doi.org/10.1016/j.brainres.2024.110894)

[accessor F, Liu Y, Sun L, et al, TASK-3 (KCNK9) and TASK-1 (KCNK3) channels in dopaminergic neurons: implications for Parkinson's disease (2022)](https://doi.org/10.1016/j.nbd.2022.105737)

[Blin S, Chatelain FC, Sandoz G, K2P channel trafficking: the long road to understanding physiology and pathology (2022)](https://doi.org/10.1016/j.tips.2022.08.003)

[Unknown, Yost J, Enyedi P, Czirják G. Two-pore domain potassium channels and their potential as drug targets (2021)](https://doi.org/10.1016/j.coph.2021.02.005)

[Rodriguez L, Zanzoni A, Catino G, et al, KCNK13 mutations associated with early-onset encephalopathy (2023)](https://doi.org/10.1002/ana.26724)

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KCNK13 Protein

KCNK13 Protein

Overview

KCNK13 Protein

Overview

Protein Information

Structure

Normal Function

Background Potassium Current

Neuronal Excitability Regulation

Tissue Distribution

Modulation

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Epilepsy

Other Neurodegenerative Conditions

Interactions and Signaling

Research Directions

See Also

External Links

References