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1.A.1.2.10
Voltage-gated K+ channel, chain A, Shaker-related, Kv1.2 or KCNA2 (Crystal structure known, Long et al., 2007; Chen et al. 2010). It functions with the auxiliary subunit, Ivβ1.2; 8.A.5.1.1) (Peters et al. 2009).  Delemotte et al. (2010) described the effects of sensor domain mutations on molecular dynamics of Kv1.2.  The Sigma 1 receptor (Q99720; Sigma non-opioid intracellular receptor 1) interacts with Kv1.2 to shape neuronal and behavioral responses to cocaine (Kourrich et al. 2013).  Amino acid substitutions cause Shaker to become heat-sensing (opens with increasing temperature as for TrpV1) or cold-sensing (opens with decreasing temperature as for TrpM8) (Chowdhury et al. 2014).  The Shaker Kv channel was truncated after the 4th transmembrane helix S4 (Shaker-iVSD) which showed altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons (Zhao and Blunck 2016).  Direct axon-to-myelin linkage by abundant KV1/Cx29 (TC# 1.A.24.1.12) channel interactions in rodent axons supports the idea of an electrically active role for myelin in increasing both the saltatory conduction velocity and the maximal propagation frequency in mammalian myelinated axons (Rash et al. 2016). A cryoEM structure (3 - 4 Å resolution; paddle chimeric channel; closed form) in nanodiscs has been determined (Matthies et al. 2018). Possible gating mechanisms have been discussed (Kariev and Green 2018; Infield et al. 2018). Pathogenic variants in KCNA2, encoding the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction (Döring et al. 2021). In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. Biophysical properties of a delayed rectifier K+ current can contribute to its role ingenerating spontaneous myogenic activity (Hu et al. 2021).

Accession Number:P16389
Protein Name:Voltage-gated potassium channel subunit Kv1.2
Length:499
Molecular Weight:56717.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:8
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

RefSeq: NP_004965.1   
Entrez Gene ID: 3737   
Pfam: PF00520    PF02214   
OMIM: 176262  gene
KEGG: hsa:3737   

Gene Ontology

GO:0044224 C:juxtaparanode region of axon
GO:0008076 C:voltage-gated potassium channel complex
GO:0005251 F:delayed rectifier potassium channel activity
GO:0006813 P:potassium ion transport
GO:0055085 P:transmembrane transport
Structure:
3lut     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTVATGDPAD EAAALPGHPQ DTYDPEADHE CCERVVINIS GLRFETQLKT LAQFPETLLG 
61:	DPKKRMRYFD PLRNEYFFDR NRPSFDAILY YYQSGGRLRR PVNVPLDIFS EEIRFYELGE 
121:	EAMEMFREDE GYIKEEERPL PENEFQRQVW LLFEYPESSG PARIIAIVSV MVILISIVSF 
181:	CLETLPIFRD ENEDMHGSGV TFHTYSNSTI GYQQSTSFTD PFFIVETLCI IWFSFEFLVR 
241:	FFACPSKAGF FTNIMNIIDI VAIIPYFITL GTELAEKPED AQQGQQAMSL AILRVIRLVR 
301:	VFRIFKLSRH SKGLQILGQT LKASMRELGL LIFFLFIGVI LFSSAVYFAE ADERESQFPS 
361:	IPDAFWWAVV SMTTVGYGDM VPTTIGGKIV GSLCAIAGVL TIALPVPVIV SNFNYFYHRE 
421:	TEGEEQAQYL QVTSCPKIPS SPDLKKSRSA STISKSDYME IQEGVNNSNE DFREENLKTA 
481:	NCTLANTNYV NITKMLTDV