ID:KCMA1_HUMAN DESCRIPTION: RecName: Full=Calcium-activated potassium channel subunit alpha-1; AltName: Full=BK channel; AltName: Full=BKCA alpha; AltName: Full=Calcium-activated potassium channel, subfamily M subunit alpha-1; AltName: Full=K(VCA)alpha; AltName: Full=KCa1.1; AltName: Full=Maxi K channel; Short=MaxiK; AltName: Full=Slo-alpha; AltName: Full=Slo1; AltName: Full=Slowpoke homolog; Short=Slo homolog; Short=hSlo; FUNCTION: Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX). ENZYME REGULATION: Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation. SUBUNIT: Homotetramer; which constitutes the calcium-activated potassium channel. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Widely expressed. Except in myocytes, it is almost ubiquitously expressed. DOMAIN: The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. DOMAIN: The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor. DOMAIN: The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium. DOMAIN: The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+) (By similarity). DOMAIN: The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors regions required for activation of the channel. DOMAIN: The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation. PTM: Phosphorylated (Probable). Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity. DISEASE: Defects in KCNMA1 are the cause of generalized epilepsy and paroxysmal dyskinesia (GEPD) [MIM:609446]. Epilepsy is one of the most common and debilitating neurological disorders. Paroxysmal dyskinesias are neurological disorders characterized by sudden, unpredictable, disabling attacks of involuntary movement often requiring life-long treatment. The coexistence of epilepsy and paroxysmal dyskinesia in the same individual or family is an increasingly recognized phenomenon. Patients manifest absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia, involuntary dystonic or choreiform movements. Onset is usually in childhood and patients may have seizures only, dyskinesia only, or both. MISCELLANEOUS: The protein was initially thought to contain two functionally distinct parts: The core channel (from the N-terminus to the S9 segment) that mediates the channel activity, and the cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the calcium sensing. The situation is however more complex, since the core channel also contains binding sites for Ca(2+) and Mg(2+). SIMILARITY: Belongs to the potassium channel family. Calcium- activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily. SIMILARITY: Contains 1 RCK N-terminal domain. SEQUENCE CAUTION: Sequence=AAA50216.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; Sequence=AAB65837.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAC50353.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAK91504.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAD06365.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q12791
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003779 actin binding GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005249 voltage-gated potassium channel activity GO:0005267 potassium channel activity GO:0005515 protein binding GO:0015269 calcium-activated potassium channel activity GO:0042802 identical protein binding GO:0046872 metal ion binding GO:0060072 large conductance calcium-activated potassium channel activity
Biological Process: GO:0001666 response to hypoxia GO:0006811 ion transport GO:0006813 potassium ion transport GO:0006970 response to osmotic stress GO:0030007 cellular potassium ion homeostasis GO:0034465 response to carbon monoxide GO:0034765 regulation of ion transmembrane transport GO:0042391 regulation of membrane potential GO:0043065 positive regulation of apoptotic process GO:0045794 negative regulation of cell volume GO:0051592 response to calcium ion GO:0055085 transmembrane transport GO:0060073 micturition GO:0060083 smooth muscle contraction involved in micturition GO:0071805 potassium ion transmembrane transport
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
