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2  structures 32  species 0  interactions 44  sequences 2  architectures

Family: K_channel_TID (PF07941)

Summary: Potassium channel Kv1.4 tandem inactivation domain

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This is the Wikipedia entry entitled "KCNA4". More...

KCNA4 Edit Wikipedia article

Potassium voltage-gated channel, shaker-related subfamily, member 4

PDB rendering based on 1kn7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KCNA4; HBK4; HK1; HPCN2; HUKII; KCNA4L; KCNA8; KV1.4; PCN2
External IDs OMIM176266 MGI96661 HomoloGene20514 IUPHAR: Kv1.4 ChEMBL: 4205 GeneCards: KCNA4 Gene
RNA expression pattern
PBB GE KCNA4 207248 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3739 16492
Ensembl ENSG00000182255 ENSMUSG00000042604
UniProt P22459 Q61423
RefSeq (mRNA) NM_002233 NM_021275
RefSeq (protein) NP_002224 NP_067250
Location (UCSC) Chr 11:
30.03 – 30.04 Mb
Chr 2:
107.29 – 107.3 Mb
PubMed search [1] [2]
Potassium channel Kv1.4 tandem inactivation domain
PDB 1kn7 EBI.jpg
solution structure of the tandem inactivation domain (residues 1-75) of potassium channel rck4 (kv1.4)
Identifiers
Symbol K_channel_TID
Pfam PF07941
InterPro IPR012897
SCOP 1kn7
SUPERFAMILY 1kn7

Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene.[1][2][3] It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.[4]

Description[edit]

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. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1 in humans.[3]

KCNA4 (Kv1.4) contains a tandem inactivation domain at the N terminus. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity.[5]

Interactions[edit]

KCNA4 has been shown to interact with DLG4,[6][7][8][9] KCNA2[10] and DLG1.[6][8][11]

See also[edit]

References[edit]

  1. ^ Philipson LH, Schaefer K, LaMendola J, Bell GI, Steiner DF (Feb 1991). "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4". Nucleic Acids Res 18 (23): 7160. doi:10.1093/nar/18.23.7160. PMC 332806. PMID 2263489. 
  2. ^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. 
  3. ^ a b "Entrez Gene: KCNA4 potassium voltage-gated channel, shaker-related subfamily, member 4". 
  4. ^ Oudit GY, Kassiri Z, Sah R, Ramirez RJ, Zobel C, Backx PH (May 2001). "The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium". J. Mol. Cell. Cardiol. 33 (5): 851–72. doi:10.1006/jmcc.2001.1376. PMID 11343410. 
  5. ^ Wissmann R, Bildl W, Oliver D, Beyermann M, Kalbitzer HR, Bentrop D, Fakler B (May 2003). "Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4". J. Biol. Chem. 278 (18): 16142–50. doi:10.1074/jbc.M210191200. PMID 12590144. 
  6. ^ a b Inanobe, Atsushi; Fujita Akikazu, Ito Minoru, Tomoike Hitonobu, Inageda Kiyoshi, Kurachi Yoshihisa (Jun 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". Am. J. Physiol., Cell Physiol. (United States) 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. ISSN 0363-6143. PMID 11997254. 
  7. ^ Niethammer, M; Valtschanoff J G, Kapoor T M, Allison D W, Weinberg R J, Craig A M, Sheng M (Apr 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron (UNITED STATES) 20 (4): 693–707. doi:10.1016/S0896-6273(00)81009-0. ISSN 0896-6273. PMID 9581762. 
  8. ^ a b Kim, E; Sheng M (1996). "Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases". Neuropharmacology (ENGLAND) 35 (7): 993–1000. doi:10.1016/0028-3908(96)00093-7. ISSN 0028-3908. PMID 8938729. 
  9. ^ Eldstrom, Jodene; Doerksen Kyle W, Steele David F, Fedida David (Nov 2002). "N-terminal PDZ-binding domain in Kv1 potassium channels". FEBS Lett. (Netherlands) 531 (3): 529–37. doi:10.1016/S0014-5793(02)03572-X. ISSN 0014-5793. PMID 12435606. 
  10. ^ Coleman, S K; Newcombe J, Pryke J, Dolly J O (Aug 1999). "Subunit composition of Kv1 channels in human CNS". J. Neurochem. (UNITED STATES) 73 (2): 849–58. doi:10.1046/j.1471-4159.1999.0730849.x. ISSN 0022-3042. PMID 10428084. 
  11. ^ Eldstrom, Jodene; Choi Woo Sung, Steele David F, Fedida David (Jul 2003). "SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism". FEBS Lett. (Netherlands) 547 (1–3): 205–11. doi:10.1016/S0014-5793(03)00668-9. ISSN 0014-5793. PMID 12860415. 

Further reading[edit]

  • Scott HS, Litjens T, Hopwood JJ, Morris CP (1993). "PCR detection of two RFLPs in exon I of the alpha-L-iduronidase (IDUA) gene.". Hum. Genet. 90 (3): 327. PMID 1362562. 
  • Gessler M, Grupe A, Grzeschik KH, Pongs O (1993). "The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene.". Hum. Genet. 90 (3): 319–21. PMID 1487251. 
  • Philipson LH, Hice RE, Schaefer K, et al. (1991). "Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel.". Proc. Natl. Acad. Sci. U.S.A. 88 (1): 53–7. doi:10.1073/pnas.88.1.53. PMC 50746. PMID 1986382. 
  • Tamkun MM, Knoth KM, Walbridge JA, et al. (1991). "Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle.". FASEB J. 5 (3): 331–7. PMID 2001794. 
  • Kim E, Niethammer M, Rothschild A, et al. (1995). "Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.". Nature 378 (6552): 85–8. doi:10.1038/378085a0. PMID 7477295. 
  • Klocke R, Roberds SL, Tamkun MM, et al. (1994). "Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal.". Genomics 18 (3): 568–74. doi:10.1016/S0888-7543(05)80358-1. PMID 7905852. 
  • Philipson LH, Eddy RL, Shows TB, Bell GI (1993). "Assignment of human potassium channel gene KCNA4 (Kv1.4, PCN2) to chromosome 11q13.4→q14.1.". Genomics 15 (2): 463–4. doi:10.1006/geno.1993.1094. PMID 8449523. 
  • Niethammer M, Kim E, Sheng M (1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases.". J. Neurosci. 16 (7): 2157–63. PMID 8601796. 
  • Kim E, Sheng M (1997). "Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases.". Neuropharmacology 35 (7): 993–1000. doi:10.1016/0028-3908(96)00093-7. PMID 8938729. 
  • Kim E, Naisbitt S, Hsueh YP, et al. (1997). "GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules.". J. Cell Biol. 136 (3): 669–78. doi:10.1083/jcb.136.3.669. PMC 2134290. PMID 9024696. 
  • Niethammer M, Valtschanoff JG, Kapoor TM, et al. (1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90.". Neuron 20 (4): 693–707. doi:10.1016/S0896-6273(00)81009-0. PMID 9581762. 
  • Brenman JE, Topinka JR, Cooper EC, et al. (1998). "Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A.". J. Neurosci. 18 (21): 8805–13. PMID 9786987. 
  • Coleman SK, Newcombe J, Pryke J, Dolly JO (1999). "Subunit composition of Kv1 channels in human CNS.". J. Neurochem. 73 (2): 849–58. doi:10.1046/j.1471-4159.1999.0730849.x. PMID 10428084. 
  • D'Adamo MC, Imbrici P, Sponcichetti F, Pessia M (1999). "Mutations in the KCNA1 gene associated with episodic ataxia type-1 syndrome impair heteromeric voltage-gated K(+) channel function.". FASEB J. 13 (11): 1335–45. PMID 10428758. 
  • Hogan A, Shepherd L, Chabot J, et al. (2001). "Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions.". J. Biol. Chem. 276 (28): 26526–33. doi:10.1074/jbc.M104156200. PMID 11352924. 
  • Cukovic D, Lu GW, Wible B, et al. (2001). "A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of alpha-actinin-2.". FEBS Lett. 498 (1): 87–92. doi:10.1016/S0014-5793(01)02505-4. PMID 11389904. 
  • Imamura F, Maeda S, Doi T, Fujiyoshi Y (2002). "Ligand binding of the second PDZ domain regulates clustering of PSD-95 with the Kv1.4 potassium channel.". J. Biol. Chem. 277 (5): 3640–6. doi:10.1074/jbc.M106940200. PMID 11723117. 
  • Piserchio A, Pellegrini M, Mehta S, et al. (2002). "The PDZ1 domain of SAP90. Characterization of structure and binding.". J. Biol. Chem. 277 (9): 6967–73. doi:10.1074/jbc.M109453200. PMID 11744724. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



This article incorporates text from the public domain Pfam and InterPro IPR012897

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Potassium channel Kv1.4 tandem inactivation domain Provide feedback

This family features the tandem inactivation domain found at the N-terminus of the Kv1.4 potassium channel. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N-terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to being about fast inactivation of the Kv1.4 channel, which is important for the channel's role in short-term plasticity [1].

Literature references

  1. Wissmann R, Bildl W, Oliver D, Beyermann M, Kalbitzer HR, Bentrop D, Fakler B; , J Biol Chem 2003;278:16142-16150.: Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4. PUBMED:12590144 EPMC:12590144


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012897

Potassium channels are the most diverse group of the ion channel family [PUBMED:1772658, PUBMED:1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PUBMED:2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PUBMED:2555158]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers [PUBMED:2448635]. In eukaryotic cells, K+ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [PUBMED:1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PUBMED:11178249].

All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)-activated K+ channels (BK, IK and SK) [PUBMED:11178249]. The 2TM domain family comprises inward-rectifying K+ channels. In addition, there are K+ channel alpha-subunits that possess two P-domains. These are usually highly regulated K+ selective leak channels.

The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential [PUBMED:10712896]. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity [PUBMED:9305895]. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.

The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression [PUBMED:11343973]. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes [PUBMED:10798390].

This entry features the tandem inactivation domain found at the N terminus of the Kv1.4 potassium channel. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity [PUBMED:12590144].

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Seed source: Pfam-B_7603 (release 14.0)
Previous IDs: none
Type: Family
Author: Fenech M
Number in seed: 2
Number in full: 44
Average length of the domain: 72.40 aa
Average identity of full alignment: 77 %
Average coverage of the sequence by the domain: 11.62 %

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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 38.4 36.7
Noise cut-off 21.9 20.0
Model length: 75
Family (HMM) version: 6
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the K_channel_TID domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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