P19024 · KCNA5_RAT
- ProteinPotassium voltage-gated channel subfamily A member 5
- GeneKcna5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids602 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:15618540, PubMed:2361015).
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:15618540).
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:15618540).
Homotetrameric channels display rapid activation and slow inactivation. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity).
May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:15618540).
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:15618540).
Homotetrameric channels display rapid activation and slow inactivation. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity).
May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
Catalytic activity
- K+(in) = K+(out)
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePotassium voltage-gated channel subfamily A member 5
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP19024
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-238 | Cytoplasmic | ||||
Sequence: MEISLVPLENGSAMTLRGGGEAGASCVQTPRGECGCPPTSGLNNQSKETLLRGRTTLEDANQGGRPLPPMAQELPQPRRLSAEDEEGEGDPGLGTVEEDQAPQDAGSLHHQRVLINISGLRFETQLGTLAQFPNTLLGDPAKRLHYFDPLRNEYFFDRNRPSFDGILYYYQSGGRLRRPVNVSLDVFADEIRFYQLGDEAMERFREDEGFIKEEEKPLPRNEFQRQVWLIFEYPESSG | ||||||
Transmembrane | 239-260 | Helical; Name=Segment S1 | ||||
Sequence: SARAIAIVSVLVILISIITFCL | ||||||
Topological domain | 261-314 | Extracellular | ||||
Sequence: ETLPEFRDERELLRHPPVPPQPPAPAPGINGSVSGALSSGPTVAPLLPRTLADP | ||||||
Transmembrane | 315-336 | Helical; Name=Segment S2 | ||||
Sequence: FFIVETTCVIWFTFELLVRFFA | ||||||
Topological domain | 337-347 | Cytoplasmic | ||||
Sequence: CPSKAEFSRNI | ||||||
Transmembrane | 348-368 | Helical; Name=Segment S3 | ||||
Sequence: MNIIDVVAIFPYFITLGTELA | ||||||
Topological domain | 369-384 | Extracellular | ||||
Sequence: EQQPGGGGQNGQQAMS | ||||||
Transmembrane | 385-405 | Helical; Voltage-sensor; Name=Segment S4 | ||||
Sequence: LAILRVIRLVRVFRIFKLSRH | ||||||
Topological domain | 406-420 | Cytoplasmic | ||||
Sequence: SKGLQILGKTLQASM | ||||||
Transmembrane | 421-442 | Helical; Name=Segment S5 | ||||
Sequence: RELGLLIFFLFIGVILFSSAVY | ||||||
Topological domain | 443-456 | Extracellular | ||||
Sequence: FAEADNHGSHFSSI | ||||||
Intramembrane | 457-468 | Helical; Name=Pore helix | ||||
Sequence: PDAFWWAVVTMT | ||||||
Intramembrane | 469-476 | |||||
Sequence: TVGYGDMR | ||||||
Topological domain | 477-483 | Extracellular | ||||
Sequence: PITVGGK | ||||||
Transmembrane | 484-512 | Helical; Name=Segment S6 | ||||
Sequence: IVGSLCAIAGVLTIALPVPVIVSNFNYFY | ||||||
Topological domain | 513-602 | Cytoplasmic | ||||
Sequence: HRETDHEEQAALKEEQGNQRRESGLDTGGQRKVSCSKASFCKTGGSLESSDSIRRGSCPLEKCHLKAKSNVDLRRSLYALCLDTSRETDL |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 600-602 | Loss of interaction with DLG1. | ||||
Sequence: TDL → AAA |
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, cross-link, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053989 | 1-602 | Potassium voltage-gated channel subfamily A member 5 | |||
Sequence: MEISLVPLENGSAMTLRGGGEAGASCVQTPRGECGCPPTSGLNNQSKETLLRGRTTLEDANQGGRPLPPMAQELPQPRRLSAEDEEGEGDPGLGTVEEDQAPQDAGSLHHQRVLINISGLRFETQLGTLAQFPNTLLGDPAKRLHYFDPLRNEYFFDRNRPSFDGILYYYQSGGRLRRPVNVSLDVFADEIRFYQLGDEAMERFREDEGFIKEEEKPLPRNEFQRQVWLIFEYPESSGSARAIAIVSVLVILISIITFCLETLPEFRDERELLRHPPVPPQPPAPAPGINGSVSGALSSGPTVAPLLPRTLADPFFIVETTCVIWFTFELLVRFFACPSKAEFSRNIMNIIDVVAIFPYFITLGTELAEQQPGGGGQNGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGKTLQASMRELGLLIFFLFIGVILFSSAVYFAEADNHGSHFSSIPDAFWWAVVTMTTVGYGDMRPITVGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETDHEEQAALKEEQGNQRRESGLDTGGQRKVSCSKASFCKTGGSLESSDSIRRGSCPLEKCHLKAKSNVDLRRSLYALCLDTSRETDL | ||||||
Modified residue | 81 | Phosphoserine; by CK2 and PKA | ||||
Sequence: S | ||||||
Cross-link | 212 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Lipidation | 337 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Cross-link | 525 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Modified residue | 535 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Modified residue | 546 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Modified residue | 569 | Phosphoserine; by PKA | ||||
Sequence: S |
Post-translational modification
Glycosylated.
Sumoylated on Lys-212, and Lys-525, preferentially with SUMO3. Sumoylation regulates the voltage sensitivity of the channel (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed equally in atrium, ventricle, aorta and skeletal muscle. Weaker expression in brain.
Induction
Expression regulated by cAMP in a tissue-specific manner. In primary cardiac cells, levels increase by 6-fold, and in GH3 cells, levels decrease 5-6-fold.
Gene expression databases
Interaction
Subunit
Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents (PubMed:11709425).
Forms a ternary complex with DLG1 and CAV3 (PubMed:15277200).
Interacts with KCNAB1 (By similarity).
Interacts with UBE2I (By similarity).
Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (By similarity).
Forms a ternary complex with DLG1 and CAV3 (PubMed:15277200).
Interacts with KCNAB1 (By similarity).
Interacts with UBE2I (By similarity).
Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-202 | Tetramerization domain | ||||
Sequence: MEISLVPLENGSAMTLRGGGEAGASCVQTPRGECGCPPTSGLNNQSKETLLRGRTTLEDANQGGRPLPPMAQELPQPRRLSAEDEEGEGDPGLGTVEEDQAPQDAGSLHHQRVLINISGLRFETQLGTLAQFPNTLLGDPAKRLHYFDPLRNEYFFDRNRPSFDGILYYYQSGGRLRRPVNVSLDVFADEIRFYQLGDEAME | ||||||
Region | 58-107 | Disordered | ||||
Sequence: EDANQGGRPLPPMAQELPQPRRLSAEDEEGEGDPGLGTVEEDQAPQDAGS | ||||||
Region | 407-420 | S4-S5 linker | ||||
Sequence: KGLQILGKTLQASM | ||||||
Motif | 469-474 | Selectivity filter | ||||
Sequence: TVGYGD | ||||||
Compositional bias | 523-539 | Basic and acidic residues | ||||
Sequence: ALKEEQGNQRRESGLDT | ||||||
Region | 523-543 | Disordered | ||||
Sequence: ALKEEQGNQRRESGLDTGGQR | ||||||
Motif | 600-602 | PDZ-binding | ||||
Sequence: TDL |
Domain
The N-terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
Sequence similarities
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length602
- Mass (Da)66,553
- Last updated1990-11-01 v1
- Checksum6A784535FF226ED7
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 523-539 | Basic and acidic residues | ||||
Sequence: ALKEEQGNQRRESGLDT | ||||||
Sequence conflict | 553 | in Ref. 2; no nucleotide entry | ||||
Sequence: C → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M27158 EMBL· GenBank· DDBJ | AAA41498.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L23434 EMBL· GenBank· DDBJ | AAA42337.1 EMBL· GenBank· DDBJ | Genomic DNA |