UniProt functional annotation for Q9UK17



	UniProt functional annotation for Q9UK17

UniProt code: Q9UK17.

Organism: Homo sapiens (Human).

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

Function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits. {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:9843794}.

Subunit: Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1. {ECO:0000250, ECO:0000269|PubMed:12297301, ECO:0000269|PubMed:14980207, ECO:0000269|PubMed:17187064, ECO:0000269|PubMed:19213956}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:Q62897}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q62897}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q62897}. Note=Interaction with palmitoylated KCNIP2 and KCNIP3 enhances cell surface expression. {ECO:0000250|UniProtKB:Q62897}.

Tissue specificity: Highly expressed in heart and brain, in particular in cortex, cerebellum, amygdala and caudate nucleus. Detected at lower levels in liver, skeletal muscle, kidney and pancreas. Isoform 1 predominates in most tissues. Isoform 1 and isoform 2 are detected at similar levels in brain, skeletal muscle and pancreas. {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:9843794}.

Domain: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Ptm: Regulated through phosphorylation at Ser-569 by CaMK2D. {ECO:0000250}.

Disease: Spinocerebellar ataxia 19 (SCA19) [MIM:607346]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis. {ECO:0000269|PubMed:23280837, ECO:0000269|PubMed:23280838, ECO:0000269|PubMed:28895081}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Brugada syndrome 9 (BRGDA9) [MIM:616399]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:21349352, ECO:0000269|PubMed:22457051}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Similarity: Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 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:		Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits. {ECO:0000269\|PubMed:10200233, ECO:0000269\|PubMed:9843794}.


Subunit:		Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1. {ECO:0000250, ECO:0000269\|PubMed:12297301, ECO:0000269\|PubMed:14980207, ECO:0000269\|PubMed:17187064, ECO:0000269\|PubMed:19213956}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:Q62897}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250\|UniProtKB:Q62897}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q62897}. Note=Interaction with palmitoylated KCNIP2 and KCNIP3 enhances cell surface expression. {ECO:0000250\|UniProtKB:Q62897}.
Tissue specificity:		Highly expressed in heart and brain, in particular in cortex, cerebellum, amygdala and caudate nucleus. Detected at lower levels in liver, skeletal muscle, kidney and pancreas. Isoform 1 predominates in most tissues. Isoform 1 and isoform 2 are detected at similar levels in brain, skeletal muscle and pancreas. {ECO:0000269\|PubMed:10200233, ECO:0000269\|PubMed:10729221, ECO:0000269\|PubMed:9843794}.
Domain:		The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Ptm:		Regulated through phosphorylation at Ser-569 by CaMK2D. {ECO:0000250}.
Disease:		Spinocerebellar ataxia 19 (SCA19) [MIM:607346]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis. {ECO:0000269\|PubMed:23280837, ECO:0000269\|PubMed:23280838, ECO:0000269\|PubMed:28895081}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Brugada syndrome 9 (BRGDA9) [MIM:616399]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269\|PubMed:21349352, ECO:0000269\|PubMed:22457051}. Note=The gene represented in this entry may be involved in disease pathogenesis.
Similarity:		Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily. {ECO:0000305}.