| 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]
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
| Disease | Target Count |
|---|---|
| Eaton-Lambert syndrome | 40 |
| Multiple Sclerosis | 498 |
| Disease | Target Count | P-value |
|---|---|---|
| lung carcinoma | 2844 | 1.17766883366383E-19 |
| pituitary cancer | 1972 | 7.17100847538183E-5 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Myasthenia Gravis | 26 | 4.334 | 2.2 |
| Thymoma | 16 | 4.228 | 2.1 |
| Episodic ataxia | 17 | 3.652 | 1.8 |
| Heart disease | 279 | 3.556 | 1.8 |
| Long QT syndrome | 53 | 3.445 | 1.7 |
| Disease | log2 FC | p |
|---|---|---|
| lung carcinoma | 2.200 | 0.000 |
| pituitary cancer | 1.300 | 0.000 |
| Accession | P22459 |
| Symbols |
HK1 HBK4 PCN2 HPCN2 HUKII KCNA8 KV1.4 KCNA4L |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Horse | EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Chicken | OMA Inparanoid |
| Anole lizard | OMA Inparanoid |
| Xenopus | OMA Inparanoid |
| PMID | Text |
|---|---|
| 22560931 | Expression of Kv1.4 appears to increase in the spinal cord of mice modelling remitting-relapsing experimental allergic encephalomyelitis (rrEAE) in peak and remitting phases. |
| 21945024 | Detection of the methylation prevalence of KCNA4 and CYP26B1 together in serum demonstrated the good sensitivity and specificityin gastric cancer |
| 21307345 | Data suggest that episodic ataxia type 1 mutations affect fast inactivation of Kv1.1/1.4 channels by a reduction in either subunit surface expression or altered affinity for the inactivation domain. |
| 19961828 | Sialylated N-glycans uniquely impact gating of a mammalian Shaker family K(v) channel isoform, K(v)1.5, but have no effect on gating of a second Shaker isoform, K(v)1.4. |
| 19453640 | Both arachidonic acid and Trolox potently modulate Kv1.4 and Kv4.2 channel alpha-subunits, thereby presumably tuning presynaptic transmitter release and postsynaptic somatodendritic excitability in synaptic transmission and plasticity. |
| 18640987 | Thr-330 of Kv1.4 serves to interlock the voltage-sensing and gating domains of adjacent monomers, thereby yielding a structure competent for the surface expression of functional tetramers |
| 17959711 | Ginsenoside Rg3 inhibits KV1.4 channel currents by interacting with the lysine531 residue. |
| 17156368 | The results demonstrate that the human Kvbeta1.1 and Kvbeta1.2 subunits regulate the proportion of wild-type Kv1.4-1.1 channels that are available to open. |
| 16308273 | Fast inactivation in human Kv1.4 is modulated by structural elements in the C-terminus, suggesting that the process involves the concerted action of the N- and C-termini. |
| 15955806 | Novel role for GIP in regulating K(V)1.4 cell surface expression and modulation of A-type potassium currents |
| More... |
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 //
| PMID | Year | Title |
|---|---|---|
| 27619418 | 2016 | Pore size matters for potassium channel conductance. |
| 22560931 | 2012 | K+ channel alterations in the progression of experimental autoimmune encephalomyelitis. |
| 21945024 | 2011 | Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis. |
| 21307345 | 2011 | Episodic ataxia type 1 mutations affect fast inactivation of K+ channels by a reduction in either subunit surface expression or affinity for inactivation domain. |
| 19968958 | 2010 | Potassium channel regulator KCNRG regulates surface expression of Shaker-type potassium channels. |
| 19961828 | 2010 | N-glycans modulate K(v)1.5 gating but have no effect on K(v)1.4 gating. |
| 19912772 | 1990 | Human potassium channel genes: Molecular cloning and functional expression. |
| 19453640 | 2009 | Arachidonic acid potently inhibits both postsynaptic-type Kv4.2 and presynaptic-type Kv1.4 IA potassium channels. |
| 18640987 | 2008 | Identification of an evolutionarily conserved extracellular threonine residue critical for surface expression and its potential coupling of adjacent voltage-sensing and gating domains in voltage-gated potassium channels. |
| 17959711 | 2008 | Ginsenoside Rg3 inhibits human Kv1.4 channel currents by interacting with the Lys531 residue. |
| More... |
