Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:9524140). 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). Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (By similarity). Extracellular magnesium ion concentrations up to 4 mM modulate channel activity by slowing down current activation in a reversible fashion. Channel activity is not regulated by cyclic nucleotides (PubMed:9524140). Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity). The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (By similarity). Interacts with RABEP1 (By similarity). Interacts (via C-terminus) with CTTN. Interacts (via C-terminal cytoplasmic region) with Ca(2+)-bound calmodulin (By similarity). Perinuclear KCNH1 is located to NPC-free islands. Detected in cerebellum, cortex and retina. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. 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. Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily.