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1.A.1.2.4
Margatoxin-sensitive voltage-gated K+ channel, Kv1.3 (in plasma and mitochondrial membranes of T lymphocytes) (Szabò et al., 2005). Kv1.3 associates with the sequence similar (>80%) Kv1.5 protein in macrophage forming heteromers that like Kv1.3 homomers are r-margatoxin sensitive (Vicente et al., 2006). However, the heteromers have different biophysical and pharmacological properties. The Kv1.3 mitochondrial potassium channel is involved in apoptotic signalling in lymphocytes (Gulbins et al., 2010). Interactions between the C-terminus  of Kv1.5 and Kvβ regulate pyridine nucleotide-dependent changes in channel gating (Tipparaju et al., 2012).  Intracellular trafficking of the KV1.3 K+ channel is regulated by the pro-domain of a matrix metalloprotease (Nguyen et al. 2013).  Direct binding of caveolin regulates Kv1 channels and allows association with lipid rafts (Pérez-Verdaguer et al. 2016). Addtionally, NavBeta1 interacts with the voltage sensing domain (VSD) of Kv1.3 through W172 in the transmembrane segment to modify the gating process (Kubota et al. 2017). During insertion of Kv1.3, the extended N-terminus of the second α-helix, S2, inside the ribosomal tunnel is converted into a helix in a transition that depends on the nascent peptide sequence at specific tunnel locations (Tu and Deutsch 2017). The microRNA, mmumiR449a, reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium activated potassium channel subunit alpha1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (Lu et al. 2017). This channel is regulation by sterols (Balajthy et al. 2017). Loss of function causes atrial fibrillation, a rhythm disorder characterized by chaotic electrical activity of cardiac atria (Olson et al. 2006). The N-terminus and S1 of Kv1.5 can attract and coassemble with the rest of the channel (i.e. Frag(304-613)) to form a functional channel independently of the S1-S2 linkage (Lamothe et al. 2018). This channel may be present in mitochondria (Parrasia et al. 2019). Kv1.3 plays an essential role in the immune response mediated by leukocytes and is functional at both the plasma membrane and the inner mitochondrial membrane. Plasma membrane Kv1.3 mediates cellular activation and proliferation, whereas mitochondrial Kv1.3 participates in cell survival and apoptosis (Capera et al. 2022). Kv1.3 uses the TIM23 complex to translocate to the inner mitochondrial membrane. This mechanism is unconventional because the channel is a multimembrane spanning protein without a defined N-terminal presequence. Transmembrane domains cooperatively mediate Kv1.3 mitochondrial targeting involving the cytosolic HSP70/HSP90 chaperone complex as a key regulator of the process (Capera et al. 2022).

Accession Number:P22001
Protein Name:Potassium voltage-gated channel subfamily A member 3
Length:575
Molecular Weight:63842.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate potassium(1+)

Cross database links:

DIP: DIP-44822N
RefSeq: NP_002223.3   
Entrez Gene ID: 3738   
Pfam: PF00520    PF02214   
OMIM: 176263  gene
KEGG: hsa:3738   

Gene Ontology

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

References (6)

[1] “Confirmation of the assignment of the gene encoding Kv1.3, a voltage-gated potassium channel (KCNA3) to the proximal short arm of human chromosome 1.”  Folander K.et.al.   7829094
[2] “The DNA sequence and biological annotation of human chromosome 1.”  Gregory S.G.et.al.   16710414
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel.”  Philipson L.H.et.al.   1986382
[5] “Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes.”  Attali B.et.al.   1373731
[6] “Characterization and functional expression of genomic DNA encoding the human lymphocyte type n potassium channel.”  Cai Y.-C.et.al.   1547020
Structure:
4BGC     

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FASTA formatted sequence
1:	MDERLSLLRS PPPPSARHRA HPPQRPASSG GAHTLVNHGY AEPAAGRELP PDMTVVPGDH 
61:	LLEPEVADGG GAPPQGGCGG GGCDRYEPLP PSLPAAGEQD CCGERVVINI SGLRFETQLK 
121:	TLCQFPETLL GDPKRRMRYF DPLRNEYFFD RNRPSFDAIL YYYQSGGRIR RPVNVPIDIF 
181:	SEEIRFYQLG EEAMEKFRED EGFLREEERP LPRRDFQRQV WLLFEYPESS GPARGIAIVS 
241:	VLVILISIVI FCLETLPEFR DEKDYPASTS QDSFEAAGNS TSGSRAGASS FSDPFFVVET 
301:	LCIIWFSFEL LVRFFACPSK ATFSRNIMNL IDIVAIIPYF ITLGTELAER QGNGQQAMSL 
361:	AILRVIRLVR VFRIFKLSRH SKGLQILGQT LKASMRELGL LIFFLFIGVI LFSSAVYFAE 
421:	ADDPTSGFSS IPDAFWWAVV TMTTVGYGDM HPVTIGGKIV GSLCAIAGVL TIALPVPVIV 
481:	SNFNYFYHRE TEGEEQSQYM HVGSCQHLSS SAEELRKARS NSTLSKSEYM VIEEGGMNHS 
541:	AFPQTPFKTG NSTATCTTNN NPNSCVNIKK IFTDV