UniProt functional annotation for Q12809



	UniProt functional annotation for Q12809

UniProt code: Q12809.

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 inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661). {ECO:0000269|PubMed:18559421, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27916661}.

Function: [Isoform A-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin- dependent degradation. {ECO:0000269|PubMed:18559421}.

Function: [Isoform B-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin- dependent degradation. {ECO:0000269|PubMed:18559421}.

Subunit: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:27916661). Interacts with DNAJB12 and DNAJB14; chaperones DNAJB12 and DNAJB14 promote tetramerization (PubMed:27916661). Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3 (By similarity). Interacts with ALG10B (By similarity). Heteromultimer with KCNE1 and KCNE2 (PubMed:9230439, PubMed:10219239). Interacts with CANX (PubMed:16361248). The core-glycosylated, but not the fully glycosylated form interacts with RNF207 (PubMed:25281747). Interacts with NDFIP1 and NDFIP2 (PubMed:26363003). {ECO:0000250|UniProtKB:O08962, ECO:0000269|PubMed:10219239, ECO:0000269|PubMed:16361248, ECO:0000269|PubMed:25281747, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:9230439}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:18559421, ECO:0000269|PubMed:19412172, ECO:0000269|PubMed:26363003}; Multi-pass membrane protein {ECO:0000269|PubMed:18559421, ECO:0000269|PubMed:19412172}.

Tissue specificity: Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells. {ECO:0000269|PubMed:18559421}.

Induction: Up-regulated by RNF207 (at protein level). {ECO:0000269|PubMed:25281747}.

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: Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction. {ECO:0000269|PubMed:10837251}.

Disease: Long QT syndrome 2 (LQT2) [MIM:613688]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2. {ECO:0000269|PubMed:10086971, ECO:0000269|PubMed:10187793, ECO:0000269|PubMed:10220144, ECO:0000269|PubMed:10517660, ECO:0000269|PubMed:10735633, ECO:0000269|PubMed:10753933, ECO:0000269|PubMed:10862094, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11170080, ECO:0000269|PubMed:12062363, ECO:0000269|PubMed:12354768, ECO:0000269|PubMed:12442276, ECO:0000269|PubMed:12621127, ECO:0000269|PubMed:15051636, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16361248, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:22314138, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:7889573, ECO:0000269|PubMed:8635257, ECO:0000269|PubMed:8877771, ECO:0000269|PubMed:8914737, ECO:0000269|PubMed:9024139, ECO:0000269|PubMed:9452080, ECO:0000269|PubMed:9544837, ECO:0000269|PubMed:9600240, ECO:0000269|PubMed:9693036}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Short QT syndrome 1 (SQT1) [MIM:609620]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. {ECO:0000269|PubMed:14676148, ECO:0000269|PubMed:15828882}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform A-USO]: Twice more abundant than isoform 1 in heart. {ECO:0000305}.

Miscellaneous: [Isoform 3.1]: Primate-specific. Lacks a domain that is crucial for slow channel deactivation. {ECO:0000305}.

Similarity: Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily. {ECO:0000305}.

Sequence caution: Sequence=CAA09232.1; Type=Erroneous gene model prediction; Evidence={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 inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661). {ECO:0000269\|PubMed:18559421, ECO:0000269\|PubMed:26363003, ECO:0000269\|PubMed:27916661}.



Function:		[Isoform A-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin- dependent degradation. {ECO:0000269\|PubMed:18559421}.



Function:		[Isoform B-USO]: Has no channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin- dependent degradation. {ECO:0000269\|PubMed:18559421}.


Subunit:		The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:27916661). Interacts with DNAJB12 and DNAJB14; chaperones DNAJB12 and DNAJB14 promote tetramerization (PubMed:27916661). Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3 (By similarity). Interacts with ALG10B (By similarity). Heteromultimer with KCNE1 and KCNE2 (PubMed:9230439, PubMed:10219239). Interacts with CANX (PubMed:16361248). The core-glycosylated, but not the fully glycosylated form interacts with RNF207 (PubMed:25281747). Interacts with NDFIP1 and NDFIP2 (PubMed:26363003). {ECO:0000250\|UniProtKB:O08962, ECO:0000269\|PubMed:10219239, ECO:0000269\|PubMed:16361248, ECO:0000269\|PubMed:25281747, ECO:0000269\|PubMed:26363003, ECO:0000269\|PubMed:27916661, ECO:0000269\|PubMed:9230439}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:18559421, ECO:0000269\|PubMed:19412172, ECO:0000269\|PubMed:26363003}; Multi-pass membrane protein {ECO:0000269\|PubMed:18559421, ECO:0000269\|PubMed:19412172}.
Tissue specificity:		Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells. {ECO:0000269\|PubMed:18559421}.
Induction:		Up-regulated by RNF207 (at protein level). {ECO:0000269\|PubMed:25281747}.
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:		Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction. {ECO:0000269\|PubMed:10837251}.
Disease:		Long QT syndrome 2 (LQT2) [MIM:613688]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2. {ECO:0000269\|PubMed:10086971, ECO:0000269\|PubMed:10187793, ECO:0000269\|PubMed:10220144, ECO:0000269\|PubMed:10517660, ECO:0000269\|PubMed:10735633, ECO:0000269\|PubMed:10753933, ECO:0000269\|PubMed:10862094, ECO:0000269\|PubMed:10973849, ECO:0000269\|PubMed:11170080, ECO:0000269\|PubMed:12062363, ECO:0000269\|PubMed:12354768, ECO:0000269\|PubMed:12442276, ECO:0000269\|PubMed:12621127, ECO:0000269\|PubMed:15051636, ECO:0000269\|PubMed:15840476, ECO:0000269\|PubMed:16361248, ECO:0000269\|PubMed:16414944, ECO:0000269\|PubMed:16922724, ECO:0000269\|PubMed:19716085, ECO:0000269\|PubMed:22314138, ECO:0000269\|PubMed:27916661, ECO:0000269\|PubMed:7889573, ECO:0000269\|PubMed:8635257, ECO:0000269\|PubMed:8877771, ECO:0000269\|PubMed:8914737, ECO:0000269\|PubMed:9024139, ECO:0000269\|PubMed:9452080, ECO:0000269\|PubMed:9544837, ECO:0000269\|PubMed:9600240, ECO:0000269\|PubMed:9693036}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Short QT syndrome 1 (SQT1) [MIM:609620]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. {ECO:0000269\|PubMed:14676148, ECO:0000269\|PubMed:15828882}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform A-USO]: Twice more abundant than isoform 1 in heart. {ECO:0000305}.
Miscellaneous:		[Isoform 3.1]: Primate-specific. Lacks a domain that is crucial for slow channel deactivation. {ECO:0000305}.
Similarity:		Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily. {ECO:0000305}.
Sequence caution:		Sequence=CAA09232.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};