The following text describes a protein:
Function:
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate. The activation kinetics depend on the prepulse potential and external divalent cation concentration. With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation. The time course of activation is biphasic with a fast and a slowly activating current component. Activates at more positive membrane potentials and exhibit a steeper activation curve (By similarity). Channel properties are modulated by subunit assembly. Mediates IK(NI) current in myoblasts. Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (By similarity).
Subcellular Localization:
Cell membrane; Multi-pass membrane protein. Nucleus inner membrane; Multi-pass membrane protein. Cell projection, dendrite. Cell projection, axon. Presynaptic cell membrane. Perikaryon. Postsynaptic density membrane. Early endosome membrane. Note=Perinuclear KCNH1 is located to NPC-free islands.
Domain:
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Conformational changes of voltage-sensor are driven by an electric field generated by a potassium gradient across the membrane; The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating; The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating. Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure; The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides. Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM; The PAS and the cyclic nucleotide-binding domain (CNBHD) interact with the transmembrane voltage sensors (VS) that modulate voltage-dependent gating and provide evidence that VS movement destabilizes these interactions to promote channel opening.
Sequence:
MTMAGGRRGLVAPQNTFLENIVRRSNDTNFVLGNAQIVDWPIVYSNDGFCKLSGYHRAEVMQKSSACSFMYGELTDKDTVEKVRQTFENYEMNSFEILMYKKNRTPVWFFVKIAPIRNEQDKVVLFLCTFSDITAFKQPIEDDSCKGWGKFARLTRALTSSRGVLQQLAPSVQKGENVHKHSRLAEVLQLGSDILPQYKQEAPKTPPHIILHYCVFKTTWDWIILILTFYTAILVPYNVSFKTRQNNVAWLVVDSIVDVIFLVDIVLNFHTTFVGPAGEVISDPKLIRMNYLKTWFVIDLLSCLPYDVINAFENVDEGISSLFSSLKVVRLLRLGRVARKLDHYIEYGAAVLVLLVCVFGLAAHWMACIWYSIGDYEIFDEDTKTIRNNSWLYQLALDIGTPYQFNGSGSGKWEGGPSKNSVYISSLYFTMTSLTSVGFGNIAPSTDIEKIFAVAIMMIGSLLYATIFGNVTTIFQQMYANTNRYHEMLNSVRDFLKLYQVPKGLSERVMDYIVSTWSMSRGIDTEKVLQICPKDMRADICVHLNRKVFKEHPAFRLASDGCLRALAMEFQTVHCAPGDLIYHAGESVDSLCFVVSGSLEVIQDDEVVAILGKGDVFGDVFWKEATLAQSCANVRALTYCDLHVIKRDALQKVLEFYTAFSHSFSRNLILTYNLRKRIVFRKISDVKREEEERMKRKNEAPLILPPDHPVRRLFQRFRQQKEARLAAERGGRDLDDLDVEKGNALTDHTSANHSLVKASVVTVRESPATPVSFQAASTSTVSDHAKLHAPGSECLGPKAGGGDPAKRKGWARFKDACGKGEDWNKVSKAESMETLPERTKASGEATLKKTDSCDSGITKSDLRLDNVGEARSPQDRSPILAEVKHSFYPIPEQTLQATVLEVKHELKEDIKALNAKMTSIEKQLSEILRILMSRGSSQSPQDTCEVSRPQSPESDRDIFGAS