P17658 · KCNA6_HUMAN
- ProteinPotassium voltage-gated channel subfamily A member 6
- GeneKCNA6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids529 (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 (PubMed:14575698, PubMed:2347305).
The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:14575698, PubMed:2347305).
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity).
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity).
Homotetrameric channels display rapid activation and slow inactivation (PubMed:2347305).
The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:14575698, PubMed:2347305).
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity).
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity).
Homotetrameric channels display rapid activation and slow inactivation (PubMed:2347305).
Catalytic activity
- K+(in) = K+(out)
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axon terminus | |
Cellular Component | cytosol | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Cellular Component | potassium channel complex | |
Cellular Component | voltage-gated potassium channel complex | |
Molecular Function | delayed rectifier potassium channel activity | |
Molecular Function | voltage-gated potassium channel activity | |
Biological Process | action potential | |
Biological Process | potassium ion transmembrane transport | |
Biological Process | potassium ion transport | |
Biological Process | protein homooligomerization |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePotassium voltage-gated channel subfamily A member 6
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP17658
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 | 1-171 | Cytoplasmic | ||||
Sequence: MRSEKSLTLAAPGEVRGPEGEQQDAGDFPEAGGGGGCCSSERLVINISGLRFETQLRTLSLFPDTLLGDPGRRVRFFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFLEEIRFYQLGDEALAAFREDEGCLPEGGEDEKPLPSQPFQRQVWLLFEYPESSG | ||||||
Transmembrane | 172-193 | Helical; Name=Segment S1 | ||||
Sequence: PARGIAIVSVLVILISIVIFCL | ||||||
Topological domain | 194-262 | Extracellular | ||||
Sequence: ETLPQFRVDGRGGNNGGVSRVSPVSRGSQEEEEDEDDSYTFHHGITPGEMGTGGSSSLSTLGGSFFTDP | ||||||
Transmembrane | 263-284 | Helical; Name=Segment S2 | ||||
Sequence: FFLVETLCIVWFTFELLVRFSA | ||||||
Topological domain | 285-295 | Cytoplasmic | ||||
Sequence: CPSKPAFFRNI | ||||||
Transmembrane | 296-316 | Helical; Name=Segment S3 | ||||
Sequence: MNIIDLVAIFPYFITLGTELV | ||||||
Topological domain | 317-337 | Extracellular | ||||
Sequence: QQQEQQPASGGGGQNGQQAMS | ||||||
Transmembrane | 338-358 | Helical; Voltage-sensor; Name=Segment S4 | ||||
Sequence: LAILRVIRLVRVFRIFKLSRH | ||||||
Topological domain | 359-373 | Cytoplasmic | ||||
Sequence: SKGLQILGKTLQASM | ||||||
Transmembrane | 374-395 | Helical; Name=Segment S5 | ||||
Sequence: RELGLLIFFLFIGVILFSSAVY | ||||||
Topological domain | 396-409 | Extracellular | ||||
Sequence: FAEADDDDSLFPSI | ||||||
Intramembrane | 410-421 | Helical; Name=Pore helix | ||||
Sequence: PDAFWWAVVTMT | ||||||
Intramembrane | 422-429 | |||||
Sequence: TVGYGDMY | ||||||
Topological domain | 430-436 | Extracellular | ||||
Sequence: PMTVGGK | ||||||
Transmembrane | 437-465 | Helical; Name=Segment S6 | ||||
Sequence: IVGSLCAIAGVLTIALPVPVIVSNFNYFY | ||||||
Topological domain | 466-529 | Cytoplasmic | ||||
Sequence: HRETEQEEQGQYTHVTCGQPAPDLRATDNGLGKPDFPEANRERRPSYLPTPHRAYAEKRMLTEV |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087560 | 261 | found in a patient with neurodevelopmental anomalies; uncertain significance | |||
Sequence: D → E | ||||||
Natural variant | VAR_087561 | 447 | found in a patient with epilepsy but without evidence of neurodevelopmental impairment; uncertain significance; affects channel properties resulting in slower channel deactivation | |||
Sequence: V → F | ||||||
Natural variant | VAR_087562 | 449 | found in a patient with epilepsy and neurodevelopmental anomalies; uncertain significance; affects channel properties resulting in slower channel deactivation | |||
Sequence: T → I | ||||||
Natural variant | VAR_087563 | 456 | found in a patient with epilepsy and neurodevelopmental anomalies; uncertain significance; affects channel properties resulting in slower channel deactivation | |||
Sequence: V → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 550 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053990 | 1-529 | Potassium voltage-gated channel subfamily A member 6 | |||
Sequence: MRSEKSLTLAAPGEVRGPEGEQQDAGDFPEAGGGGGCCSSERLVINISGLRFETQLRTLSLFPDTLLGDPGRRVRFFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFLEEIRFYQLGDEALAAFREDEGCLPEGGEDEKPLPSQPFQRQVWLLFEYPESSGPARGIAIVSVLVILISIVIFCLETLPQFRVDGRGGNNGGVSRVSPVSRGSQEEEEDEDDSYTFHHGITPGEMGTGGSSSLSTLGGSFFTDPFFLVETLCIVWFTFELLVRFSACPSKPAFFRNIMNIIDLVAIFPYFITLGTELVQQQEQQPASGGGGQNGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGKTLQASMRELGLLIFFLFIGVILFSSAVYFAEADDDDSLFPSIPDAFWWAVVTMTTVGYGDMYPMTVGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEQEEQGQYTHVTCGQPAPDLRATDNGLGKPDFPEANRERRPSYLPTPHRAYAEKRMLTEV | ||||||
Modified residue | 3 | Phosphoserine | ||||
Sequence: S | ||||||
Lipidation | 285 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 511 | Phosphoserine; by PKA | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homotetramer and heterotetramer of potassium channel proteins (By similarity).
Interacts with KCNAB1 and KCNAB2 (By similarity).
Interacts with KCNAB1 and KCNAB2 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P17658 | DOLK Q9UPQ8 | 6 | EBI-6426142, EBI-8645574 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-33 | Disordered | ||||
Sequence: MRSEKSLTLAAPGEVRGPEGEQQDAGDFPEAGG | ||||||
Region | 210-233 | Disordered | ||||
Sequence: GVSRVSPVSRGSQEEEEDEDDSYT | ||||||
Region | 360-373 | S4-S5 linker | ||||
Sequence: KGLQILGKTLQASM | ||||||
Motif | 422-427 | Selectivity filter | ||||
Sequence: TVGYGD | ||||||
Region | 488-513 | Disordered | ||||
Sequence: DLRATDNGLGKPDFPEANRERRPSYL | ||||||
Motif | 527-529 | PDZ-binding | ||||
Sequence: TEV |
Domain
The N-terminus may be important in determining the rate of inactivation of the channel while the tail 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. Kv1.6/KCNA6 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length529
- Mass (Da)58,729
- Last updated1990-08-01 v1
- ChecksumCFF0710A1F9CD69F
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X17622 EMBL· GenBank· DDBJ | CAA35623.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069355 EMBL· GenBank· DDBJ | AAH69355.1 EMBL· GenBank· DDBJ | mRNA |