UniProt functional annotation for P56696



	UniProt functional annotation for P56696

UniProt code: P56696.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.

Subunit: Homotetramer. May form heteromultimers with KCNQ3. Interacts with HSP90AB1; promotes cell surface expression of KCNQ4 (PubMed:23431407). {ECO:0000269|PubMed:17329207, ECO:0000269|PubMed:23431407}.

Subcellular location: Basal cell membrane; Multi-pass membrane protein. Note=Situated at the basal membrane of cochlear outer hair cells. {ECO:0000250}.

Tissue specificity: Expressed in the outer, but not the inner, sensory hair cells of the cochlea. Slightly expressed in heart, brain and skeletal muscle.

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:0000250}.

Domain: The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded. {ECO:0000269|PubMed:17329207}.

Disease: Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Mutagenesis experiments were carried out by expressing in Xenopus oocytes KCNQ4 mutants either individually (homomultimers) or in combination with wild-type KCNQ4 (mut/wt homomultimers) in a ratio of 1:1, to mimic the situation in a heterozygous DFNA2 patient.

Similarity: Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.4/KCNQ4 sub-subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.


Subunit:		Homotetramer. May form heteromultimers with KCNQ3. Interacts with HSP90AB1; promotes cell surface expression of KCNQ4 (PubMed:23431407). {ECO:0000269\|PubMed:17329207, ECO:0000269\|PubMed:23431407}.
Subcellular location:		Basal cell membrane; Multi-pass membrane protein. Note=Situated at the basal membrane of cochlear outer hair cells. {ECO:0000250}.
Tissue specificity:		Expressed in the outer, but not the inner, sensory hair cells of the cochlea. Slightly expressed in heart, brain and skeletal muscle.
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:0000250}.
Domain:		The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded. {ECO:0000269\|PubMed:17329207}.
Disease:		Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269\|PubMed:10025409, ECO:0000269\|PubMed:10369879, ECO:0000269\|PubMed:10571947, ECO:0000269\|PubMed:10925378, ECO:0000269\|PubMed:21242547}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Mutagenesis experiments were carried out by expressing in Xenopus oocytes KCNQ4 mutants either individually (homomultimers) or in combination with wild-type KCNQ4 (mut/wt homomultimers) in a ratio of 1:1, to mimic the situation in a heterozygous DFNA2 patient.
Similarity:		Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.4/KCNQ4 sub-subfamily. {ECO:0000305}.