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  4. Potassium channel family
  5. A (Shaker) subfamily
  6. Kv1.4-KCNA4 sub-subfamily
  7. Potassium voltage-gated channel subfamily A member 4

Tclin Potassium voltage-gated channel subfamily A member 4

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:19912772, PubMed:8495559). 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:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential.[provided by RefSeq, Mar 2011]

 Comments

Property Summary

Ligand Count 9
NCBI Gene PubMed Count 43
PubMed Score 199.78
PubTator Score 108.35

Knowledge Summary

Patent (10,492)

TINX Plot

  Disease (4)

Disease Target Count P-value
lung carcinoma 2843 1.2e-19
pituitary cancer 1972 7.2e-05
Disease Target Count Z-score Confidence
Carcinoma 11493 0.0 1.3
Kidney cancer 2613 0.0 0.7
Liver cancer 604 0.0 0.5
lung cancer 4740 0.0 0.6

Expression

  Differential Expression (2)

Disease log2 FC p
lung carcinoma 2.200 1.2e-19
pituitary cancer 1.300 7.2e-05

Synonym

Accession P22459
Symbols HK1
HBK4
PCN2
HPCN2
HUKII
KCNA8
KV1.4
KCNA4L

Gene

KCNA4

  Ortholog (11)

Species Source Disease
Inparanoid OMA
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid EggNOG
Inparanoid OMA EggNOG
OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA
Inparanoid OMA

 UniProt Keyword (16)

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 GO Function (2)

 GO Component (5)

 GO Process (3)

 Compartment GO Term (25)

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 MGI Phenotype (2)

 HCA RNA Cell Line (18)

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Pathway (5)

Drug (2)

Structure of guanidine

guanidine

Structure of amifampridine

amifampridine

Ligand (6)

Structure of fampridine

fampridine
pIC50 1.90

Structure of CHEMBL408488

CHEMBL408488
pEC50 5.64

Structure of CHEMBL259345

CHEMBL259345
pEC50 5.89

Structure of CP-339818

CP-339818
6.50

Structure of nicardipine

nicardipine
6.10

Structure of quinidine

quinidine
3.70

Gene RIF (12)

AA Sequence 

MEVAMVSAESSGCNSHMPYGYAAQARARERERLAHSRAAAAAAVAAATAAVEGSGGSGGGSHHHHQSRGA      1 - 70
CTSHDPQSSRGSRRRRRQRSEKKKAHYRQSSFPHCSDLMPSGSEEKILRELSEEEEDEEEEEEEEEEGRF     71 - 140
YYSEDDHGDECSYTDLLPQDEGGGGYSSVRYSDCCERVVINVSGLRFETQMKTLAQFPETLLGDPEKRTQ    141 - 210
YFDPLRNEYFFDRNRPSFDAILYYYQSGGRLKRPVNVPFDIFTEEVKFYQLGEEALLKFREDEGFVREEE    211 - 280
DRALPENEFKKQIWLLFEYPESSSPARGIAIVSVLVILISIVIFCLETLPEFRDDRDLVMALSAGGHGGL    281 - 350
LNDTSAPHLENSGHTIFNDPFFIVETVCIVWFSFEFVVRCFACPSQALFFKNIMNIIDIVSILPYFITLG    351 - 420
TDLAQQQGGGNGQQQQAMSFAILRIIRLVRVFRIFKLSRHSKGLQILGHTLRASMRELGLLIFFLFIGVI    421 - 490
LFSSAVYFAEADEPTTHFQSIPDAFWWAVVTMTTVGYGDMKPITVGGKIVGSLCAIAGVLTIALPVPVIV    491 - 560
SNFNYFYHRETENEEQTQLTQNAVSCPYLPSNLLKKFRSSTSSSLGDKSEYLEMEEGVKESLCAKEEKCQ    561 - 630
GKGDDSETDKNNCSNAKAVETDV                                                   631 - 653
//

Text Mined References (45)

PMID Year Title