UniProt functional annotation for Q63472



	UniProt functional annotation for Q63472

UniProt code: Q63472.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:7925287, PubMed:9400421, PubMed:24495567, PubMed:27516594). 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). {ECO:0000250|UniProtKB:O95259, ECO:0000269|PubMed:24495567, ECO:0000269|PubMed:27516594, ECO:0000269|PubMed:7925287, ECO:0000269|PubMed:9400421}.

Activity regulation: Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin (PubMed:27516594). Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure. Channel activity is not regulated by cyclic nucleotides. 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). {ECO:0000250|UniProtKB:O95259, ECO:0000250|UniProtKB:Q60603, ECO:0000269|PubMed:27516594}.

Subunit: The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:9400421, PubMed:27516594). Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (PubMed:9722534). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN (PubMed:23144454). Interacts (via cytoplasmic region) with Ca(2+)-bound calmodulin (PubMed:27516594). {ECO:0000250|UniProtKB:O95259, ECO:0000269|PubMed:22841712, ECO:0000269|PubMed:23144454, ECO:0000269|PubMed:27516594, ECO:0000269|PubMed:9400421, ECO:0000269|PubMed:9722534}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:24495567, ECO:0000269|PubMed:27516594, ECO:0000269|PubMed:7925287, ECO:0000269|PubMed:9400421}; Multi-pass membrane protein {ECO:0000269|PubMed:27516594}. Nucleus inner membrane {ECO:0000250|UniProtKB:O95259}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O95259}. Cell projection, dendrite {ECO:0000269|PubMed:24495567}. Cell projection, axon {ECO:0000269|PubMed:24495567}. Cell junction, synapse, presynaptic cell membrane {ECO:0000269|PubMed:25556795}. Perikaryon {ECO:0000269|PubMed:24495567}. Cell junction, synapse, postsynaptic density membrane {ECO:0000269|PubMed:24495567}. Early endosome membrane {ECO:0000250|UniProtKB:O95259}. Note=Perinuclear KCNH1 is located to NPC-free islands. {ECO:0000250|UniProtKB:O95259}.

Tissue specificity: Detected in cerebellum, at parallel fiber synapses on Purkinje cell spines (PubMed:25556795). Detected in hippocampus neurons (at protein level) (PubMed:24495567). Detected in brain, but not in the other tissues tested; expression is highest in granular cells of the dentate gyrus, in hippocampus CA3 pyramidal cells, and in cerebellar granule cells (PubMed:7925287). Detected in pituitary (PubMed:10718922). {ECO:0000269|PubMed:10718922, ECO:0000269|PubMed:24495567, ECO:0000269|PubMed:25556795, ECO:0000269|PubMed:7925287}.

Domain: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. {ECO:0000269|PubMed:9400421}.

Domain: The C-terminal region interacts with the cyclic nucleotide- binding domain and contributes to regulate channel gating. {ECO:0000250|UniProtKB:Q60603}.

Domain: 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. {ECO:0000269|PubMed:27516594}.

Domain: 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. {ECO:0000250|UniProtKB:Q60603}.

Ptm: Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6. {ECO:0000250|UniProtKB:O95259}.

Similarity: Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:7925287, PubMed:9400421, PubMed:24495567, PubMed:27516594). 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). {ECO:0000250\|UniProtKB:O95259, ECO:0000269\|PubMed:24495567, ECO:0000269\|PubMed:27516594, ECO:0000269\|PubMed:7925287, ECO:0000269\|PubMed:9400421}.


Activity regulation:		Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin (PubMed:27516594). Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure. Channel activity is not regulated by cyclic nucleotides. 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). {ECO:0000250\|UniProtKB:O95259, ECO:0000250\|UniProtKB:Q60603, ECO:0000269\|PubMed:27516594}.
Subunit:		The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:9400421, PubMed:27516594). Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (PubMed:9722534). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN (PubMed:23144454). Interacts (via cytoplasmic region) with Ca(2+)-bound calmodulin (PubMed:27516594). {ECO:0000250\|UniProtKB:O95259, ECO:0000269\|PubMed:22841712, ECO:0000269\|PubMed:23144454, ECO:0000269\|PubMed:27516594, ECO:0000269\|PubMed:9400421, ECO:0000269\|PubMed:9722534}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:24495567, ECO:0000269\|PubMed:27516594, ECO:0000269\|PubMed:7925287, ECO:0000269\|PubMed:9400421}; Multi-pass membrane protein {ECO:0000269\|PubMed:27516594}. Nucleus inner membrane {ECO:0000250\|UniProtKB:O95259}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:O95259}. Cell projection, dendrite {ECO:0000269\|PubMed:24495567}. Cell projection, axon {ECO:0000269\|PubMed:24495567}. Cell junction, synapse, presynaptic cell membrane {ECO:0000269\|PubMed:25556795}. Perikaryon {ECO:0000269\|PubMed:24495567}. Cell junction, synapse, postsynaptic density membrane {ECO:0000269\|PubMed:24495567}. Early endosome membrane {ECO:0000250\|UniProtKB:O95259}. Note=Perinuclear KCNH1 is located to NPC-free islands. {ECO:0000250\|UniProtKB:O95259}.
Tissue specificity:		Detected in cerebellum, at parallel fiber synapses on Purkinje cell spines (PubMed:25556795). Detected in hippocampus neurons (at protein level) (PubMed:24495567). Detected in brain, but not in the other tissues tested; expression is highest in granular cells of the dentate gyrus, in hippocampus CA3 pyramidal cells, and in cerebellar granule cells (PubMed:7925287). Detected in pituitary (PubMed:10718922). {ECO:0000269\|PubMed:10718922, ECO:0000269\|PubMed:24495567, ECO:0000269\|PubMed:25556795, ECO:0000269\|PubMed:7925287}.
Domain:		The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. {ECO:0000269\|PubMed:9400421}.
Domain:		The C-terminal region interacts with the cyclic nucleotide- binding domain and contributes to regulate channel gating. {ECO:0000250\|UniProtKB:Q60603}.
Domain:		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. {ECO:0000269\|PubMed:27516594}.
Domain:		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. {ECO:0000250\|UniProtKB:Q60603}.
Ptm:		Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6. {ECO:0000250\|UniProtKB:O95259}.
Similarity:		Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily. {ECO:0000305}.