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1.A.1.2.5
Voltage-gated K+ channel subfamily D, member 2, Kv4.2 or KCND2, in neurons and muscle; forms complexes with auxiliary subunits and scaffolding proteins via its N-terminus, influencing trafficking, temperature-sensitivity and gating (Radicke et al. 2013).These subunits are (1) dipeptidyl-peptidase-like type II transmembrane proteins typified by DPPX-S (e.g., protein 6, P42658; 865 aas), and (2) cytoplasmic Ca2+ binding proteins known as K+ channel interacting proteins (KChIPs; TC#5.B.1.1.7; Q6PIL6) (Seikel and Trimmer 2009).  The C-terminus interacts with KChIP2 to influence gating, surface trafficking and gene expression (Han et al., 2006; Schwenk et al., 2008). KChIPs (250 aas for mouse KChIP4a; Q6PHZ8) are homologous to domains in NADPH oxidases (5.B.1). Heteropoda toxin 2 (P58426; PDB 1EMX; TC#8.B.5.2.2) interactions with Kv4.3 and Kv4.1 give rise to differences in gating modifications (DeSimone et al., 2011).  Mutations cause autism and seizures due to a slowing of channel inactivation (Lee et al. 2014).  The stoichiometry of Kv4.2 and DPP6 is 4:4 (Soh and Goldstein 2008). Neferine, an isoquinoline alkaloid from plants, inhibits Kv4.3 channels, probably by blocking the open state (Wang et al. 2015).

Accession Number:Q9NZV8
Protein Name:Voltage-gated potassium channel subunit Kv4.2
Length:630
Molecular Weight:70537.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: Q9NZV8
RefSeq: NP_036413.1   
Entrez Gene ID: 3751   
Pfam: PF00520    PF02214    PF11601   
Drugbank: Drugbank Link   
OMIM: 605410  gene
KEGG: hsa:3751   

Gene Ontology

GO:0009986 C:cell surface
GO:0043197 C:dendritic spine
GO:0008076 C:voltage-gated potassium channel complex
GO:0046872 F:metal ion binding
GO:0006813 P:potassium ion transport
GO:0001508 P:regulation of action potential
GO:0007268 P:synaptic transmission
GO:0055085 P:transmembrane transport

References (17)

[1] “Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing.”  Kong W.et.al.   9843794
[2] “Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.”  Kikuno R.et.al.   10470851
[3] “Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current.”  Zhu X.-R.et.al.   10551270
[4] “Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA).”  Isbrandt D.et.al.   10729221
[5] “The DNA sequence of human chromosome 7.”  Hillier L.W.et.al.   12853948
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Localization and enhanced current density of the Kv4.2 potassium channel by interaction with the actin-binding protein filamin.”  Petrecca K.et.al.   11102480
[8] “Modulation of A-type potassium channels by a family of calcium sensors.”  An W.F.et.al.   10676964
[9] “Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.”  Baehring R.et.al.   11287421
[10] “Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4.”  Morohashi Y.et.al.   11847232
[11] “PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex.”  Schrader L.A.et.al.   12451113
[12] “Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10).”  Jerng H.H.et.al.   15454437
[13] “Protein-protein interactions of KChIP proteins and Kv4.2.”  Lin Y.-L.et.al.   15358149
[14] “Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2.”  Kim L.A.et.al.   14623880
[15] “Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by electron microscopy at 21 Angstrom resolution.”  Kim L.A.et.al.   14980201
[16] “Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1.”  Scannevin R.H.et.al.   14980207
[17] “Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes.”  El-Haou S.et.al.   19213956

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE 
61:	RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA 
121:	FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDTAGES ALPTMTARQR VWRAFENPHT 
181:	STMALVFYYV TGFFIAVSVI ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF 
241:	TVEYLLRLAA APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI 
301:	FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS ASKFTSIPAA 
361:	FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL PVPVIVSNFS RIYHQNQRAD 
421:	KRRAQKKARL ARIRAAKSGS ANAYMQSKRN GLLSNQLQSS EDEQAFVSKS GSSFETQHHH 
481:	LLHCLEKTTN HEFVDEQVFE ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKTFRI 
541:	PNANVSGSHQ GSIQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI 
601:	PTPPVTTPEG DDRPESPEYS GGNIVRVSAL