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KCNA1_HUMAN

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed, PubMed). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed, PubMed). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed, PubMed, PubMed, PubMed). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons . May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons . May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release . Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction . Required for normal neuromuscular responses (PubMed, PubMed). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli . Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception . The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine . Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain . Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed, PubMed). [View more on UniProt]

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Position Amino acid Mutation Disease Overlap with binding region
174 Val Phe Episodicataxia1(EA1) -
177 Ile Arg Episodicataxia1(EA1) -
226 Thr Ala Episodicataxia1(EA1) -
239 Arg Ser Episodicataxia1(EA1) -
249 Phe Ile Episodicataxia1(EA1) -
404 Val Ile Episodicataxia1(EA1) -
408 Val Ala Episodicataxia1(EA1) -
184 Phe Cys Episodicataxia1(EA1) -
226 Thr Met Episodicataxia1(EA1) -
325 Glu Asp Episodicataxia1(EA1) -
329 Leu Ile Episodicataxia1(EA1) -
342 Ser Ile Episodicataxia1(EA1) -
226 Thr Lys Myokymiaisolated1(MK1) -
226 Thr Arg Episodicataxia1(EA1) -
242 Ala Pro Myokymiaisolated1(MK1) -
244 Pro His Myokymiaisolated1(MK1) -
255 Asn Asp Myokymiaisolated1(MK1) -
405 Pro Leu - -

No annotated instance was found. To search for linear motifs, use the ELM prediction server.

Molecular function

Term Name % Distance from the top of the tree Annotated in KCNA1_HUMAN
GO:0005216 ion channel activity 50.0000 4 yes
GO:0005244 voltage-gated ion channel activity 50.0000 4 yes
GO:0005261 cation channel activity 50.0000 5 yes
GO:0008324 cation transmembrane transporter activity 50.0000 4 yes
GO:0015267 channel activity 50.0000 4 yes
GO:0022832 voltage-gated channel activity 50.0000 6 yes
GO:0022836 gated channel activity 50.0000 5 yes
GO:0022890 inorganic cation transmembrane transporter activity 50.0000 4 yes
GO:0046873 metal ion transmembrane transporter activity 50.0000 5 yes
GO:0005249 voltage-gated potassium channel activity 40.9091 6 yes
GO:0005267 potassium channel activity 40.9091 6 yes
GO:0015079 potassium ion transmembrane transporter activity 40.9091 6 yes
GO:0022843 voltage-gated cation channel activity 40.9091 5 yes
GO:0005251 delayed rectifier potassium channel activity 36.3636 7 yes
GO:0097718 disordered domain specific binding 9.0909 4 yes
GO:0099508 voltage-gated ion channel activity involved in regulation of presynaptic membrane potential 9.0909 5 yes
GO:1905030 voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential 9.0909 5 yes

Biological process

Term Name % Distance from top the of the tree Annotated in KCNA1_HUMAN
GO:0043269 regulation of ion transport 59.0909 5 yes
GO:0051049 regulation of transport 59.0909 4 yes
GO:0034762 regulation of transmembrane transport 54.5455 4 yes
GO:0034765 regulation of ion transmembrane transport 54.5455 5 yes
GO:0006811 ion transport 45.4545 4 yes
GO:0006812 cation transport 45.4545 5 yes
GO:0008104 protein localization 45.4545 4 yes
GO:0022607 cellular component assembly 45.4545 4 yes
GO:0030001 metal ion transport 45.4545 6 yes
GO:0098655 cation transmembrane transport 45.4545 4 yes
GO:0098660 inorganic ion transmembrane transport 45.4545 4 yes
GO:0098662 inorganic cation transmembrane transport 45.4545 5 yes
GO:0043933 protein-containing complex organization 40.9091 4 yes
GO:0048522 positive regulation of cellular process 40.9091 4 yes
GO:0065003 protein-containing complex assembly 40.9091 5 yes
GO:0006813 potassium ion transport 36.3636 7 yes
GO:0071805 potassium ion transmembrane transport 36.3636 6 yes
GO:0001508 action potential 31.8182 4 yes
GO:0051259 protein complex oligomerization 27.2727 6 yes
GO:0051260 protein homooligomerization 27.2727 7 yes
GO:0010646 regulation of cell communication 27.2727 4 no
GO:0007268 chemical synaptic transmission 22.7273 6 yes
GO:0019228 neuronal action potential 22.7273 5 yes
GO:0044057 regulation of system process 22.7273 4 yes
GO:0098916 anterograde trans-synaptic signaling 22.7273 5 yes
GO:0099537 trans-synaptic signaling 22.7273 4 yes
GO:0048523 negative regulation of cellular process 22.7273 4 no
GO:0072657 protein localization to membrane 22.7273 4 no
GO:0032880 regulation of protein localization 22.7273 5 no
GO:0050804 modulation of chemical synaptic transmission 22.7273 5 no
GO:0060341 regulation of cellular localization 22.7273 4 no
GO:0099177 regulation of trans-synaptic signaling 22.7273 4 no
GO:0051128 regulation of cellular component organization 22.7273 4 no
GO:0030030 cell projection organization 22.7273 4 no
GO:0007399 nervous system development 22.7273 4 no
GO:0010038 response to metal ion 18.1818 4 yes
GO:0043270 positive regulation of ion transport 18.1818 5 yes
GO:0048878 chemical homeostasis 18.1818 4 yes
GO:0050905 neuromuscular process 18.1818 4 yes
GO:0051050 positive regulation of transport 18.1818 4 yes
GO:0071241 cellular response to inorganic substance 18.1818 4 yes
GO:0071248 cellular response to metal ion 18.1818 5 yes
GO:1904062 regulation of cation transmembrane transport 18.1818 6 yes
GO:0010959 regulation of metal ion transport 13.6364 6 yes
GO:0022898 regulation of transmembrane transporter activity 13.6364 4 yes
GO:0032412 regulation of ion transmembrane transporter activity 13.6364 5 yes
GO:0043266 regulation of potassium ion transport 13.6364 7 yes
GO:1901379 regulation of potassium ion transmembrane transport 13.6364 7 yes
GO:2001257 regulation of cation channel activity 13.6364 6 yes
GO:0006937 regulation of muscle contraction 9.0909 6 yes
GO:0007405 neuroblast proliferation 9.0909 4 yes
GO:0010960 magnesium ion homeostasis 9.0909 8 yes
GO:0032026 response to magnesium ion 9.0909 5 yes
GO:0032411 positive regulation of transporter activity 9.0909 4 yes
GO:0032414 positive regulation of ion transmembrane transporter activity 9.0909 5 yes
GO:0034764 positive regulation of transmembrane transport 9.0909 5 yes
GO:0034767 positive regulation of ion transmembrane transport 9.0909 6 yes
GO:0043268 positive regulation of potassium ion transport 9.0909 6 yes
GO:0050801 ion homeostasis 9.0909 5 yes
GO:0050966 detection of mechanical stimulus involved in sensory perception of pain 9.0909 5 yes
GO:0050974 detection of mechanical stimulus involved in sensory perception 9.0909 4 yes
GO:0050976 detection of mechanical stimulus involved in sensory perception of touch 9.0909 5 yes
GO:0050982 detection of mechanical stimulus 9.0909 4 yes
GO:0055065 metal ion homeostasis 9.0909 7 yes
GO:0055080 cation homeostasis 9.0909 6 yes
GO:0062149 detection of stimulus involved in sensory perception of pain 9.0909 4 yes
GO:0071286 cellular response to magnesium ion 9.0909 6 yes
GO:0072507 divalent inorganic cation homeostasis 9.0909 7 yes
GO:0090257 regulation of muscle system process 9.0909 5 yes
GO:0098771 inorganic ion homeostasis 9.0909 6 yes
GO:1901016 regulation of potassium ion transmembrane transporter activity 9.0909 6 yes
GO:1901018 positive regulation of potassium ion transmembrane transporter activity 9.0909 6 yes
GO:1901381 positive regulation of potassium ion transmembrane transport 9.0909 7 yes
GO:1903818 positive regulation of voltage-gated potassium channel activity 9.0909 7 yes
GO:1904064 positive regulation of cation transmembrane transport 9.0909 7 yes
GO:2001259 positive regulation of cation channel activity 9.0909 6 yes

Disease

Term Name % Distance from top the of the tree Annotated in KCNA1_HUMAN
DOID:331 central nervous system disease 36.3636 3 yes
DOID:1826 epilepsy 27.2727 5 no
DOID:936 brain disease 27.2727 4 no
DOID:0050701 electroclinical syndrome 22.7273 6 no
DOID:0112202 developmental and epileptic encephalopathy 22.7273 7 no
DOID:0050951 hereditary ataxia 9.0909 5 yes
DOID:0050989 episodic ataxia type 1 9.0909 7 yes
DOID:1289 neurodegenerative disease 9.0909 4 yes
DOID:963 episodic ataxia 9.0909 6 yes
DOID:0050703 infancy electroclinical syndrome 9.0909 7 no
DOID:0060169 benign familial infantile epilepsy 9.0909 8 no
Uniprot ID Details Highest evidence Localizing into PSD HPA (protein expression in neurons)
DLG4_HUMAN [view entry] [view interactions] Low throughput yes yes
KCAB2_HUMAN [view entry] [view interactions] Low throughput yes yes
KCNA3_HUMAN [view entry] [view interactions] Low throughput yes no
KCNA1_HUMAN [view entry] [view interactions] Low throughput yes yes
CNTP1_HUMAN [view entry] [view interactions] Low throughput yes yes
RTN4_HUMAN [view entry] [view interactions] Low throughput yes yes
KCNA2_HUMAN [view entry] [view interactions] Low throughput yes yes
KCNA4_HUMAN [view entry] [view interactions] Low throughput yes yes
KCNRG_HUMAN [view interactions] Low throughput no no
DLG3_HUMAN [view entry] [view interactions] High throughput yes yes
DLGP1_HUMAN [view entry] [view interactions] High throughput yes no
ITM2B_HUMAN [view interactions] High throughput no yes
MAL_HUMAN [view interactions] High throughput no no
IR3IP_HUMAN [view interactions] High throughput no yes
TM14B_HUMAN [view interactions] High throughput no no
APOL2_HUMAN [view entry] [view interactions] High throughput yes yes
TM86A_HUMAN [view interactions] High throughput no yes
JAGN1_HUMAN [view interactions] High throughput no no
SGTA_HUMAN [view interactions] High throughput no yes
KCA10_HUMAN [view interactions] High throughput no no
GPR42_HUMAN [view interactions] High throughput no no
DOLK_HUMAN [view interactions] High throughput no no
GP152_HUMAN [view interactions] High throughput no no
FCERG_HUMAN [view interactions] High throughput no no
UBC_HUMAN [view entry] [view interactions] High throughput yes yes
KPCD2_HUMAN [view interactions] High throughput no yes
KCNS1_HUMAN [view interactions] High throughput no no
KCNS2_HUMAN [view interactions] High throughput no no
KCAB1_HUMAN [view interactions] High throughput no no
KCNB1_HUMAN [view entry] [view interactions] High throughput yes yes
KCNQ2_HUMAN [view entry] [view interactions] High throughput yes yes
ADA22_HUMAN [view entry] [view interactions] Computational yes no
SCN8A_HUMAN [view entry] [view interactions] Computational yes no
KCAB3_HUMAN [view interactions] Computational no no
KCNH2_HUMAN [view interactions] Computational no no
CAC1A_HUMAN [view interactions] Computational no no
LGI1_HUMAN [view entry] [view interactions] Computational yes no
CNTP2_HUMAN [view entry] [view interactions] Computational yes yes
SCN2A_HUMAN [view entry] [view interactions] Computational yes yes
KCNH1_HUMAN [view entry] [view interactions] Computational yes yes
STX1A_HUMAN [view entry] [view interactions] Computational yes yes