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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:P22460
Protein Name:Potassium voltage-gated channel subfamily A member 5
Length:613
Molecular Weight:67228.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate potassium(1+)

Cross database links:

RefSeq: NP_002225.2   
Entrez Gene ID: 3741   
Pfam: PF00520    PF02214   
OMIM: 176267  gene
612240  phenotype
KEGG: hsa:3741   

Gene Ontology

GO:0005794 C:Golgi apparatus
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 (11)

[1] “Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle.”  Tamkun M.M.et.al.   2001794
[2] “Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel.”  Philipson L.H.et.al.   1986382
[3] “Molecular cloning, characterization, and genomic localization of a human potassium channel gene.”  Curran M.E.et.al.   1349297
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression.”  Snyders D.J.et.al.   8505626
[6] “Altered state dependence of c-type inactivation in the long and short forms of human Kv1.5.”  Kurata H.T.et.al.   11524461
[7] “A specific N-terminal residue in Kv1.5 is required for upregulation of the channel by SAP97.”  Mathur R.et.al.   16466689
[8] “Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation.”  Olson T.M.et.al.   16772329
[9] “SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5.”  Benson M.D.et.al.   17261810
[10] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330
[11] “The consensus coding sequences of human breast and colorectal cancers.”  Sjoeblom T.et.al.   16959974

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEIALVPLEN GGAMTVRGGD EARAGCGQAT GGELQCPPTA GLSDGPKEPA PKGRGAQRDA 
61:	DSGVRPLPPL PDPGVRPLPP LPEELPRPRR PPPEDEEEEG DPGLGTVEDQ ALGTASLHHQ 
121:	RVHINISGLR FETQLGTLAQ FPNTLLGDPA KRLRYFDPLR NEYFFDRNRP SFDGILYYYQ 
181:	SGGRLRRPVN VSLDVFADEI RFYQLGDEAM ERFREDEGFI KEEEKPLPRN EFQRQVWLIF 
241:	EYPESSGSAR AIAIVSVLVI LISIITFCLE TLPEFRDERE LLRHPPAPHQ PPAPAPGANG 
301:	SGVMAPPSGP TVAPLLPRTL ADPFFIVETT CVIWFTFELL VRFFACPSKA GFSRNIMNII 
361:	DVVAIFPYFI TLGTELAEQQ PGGGGGGQNG QQAMSLAILR VIRLVRVFRI FKLSRHSKGL 
421:	QILGKTLQAS MRELGLLIFF LFIGVILFSS AVYFAEADNQ GTHFSSIPDA FWWAVVTMTT 
481:	VGYGDMRPIT VGGKIVGSLC AIAGVLTIAL PVPVIVSNFN YFYHRETDHE EPAVLKEEQG 
541:	TQSQGPGLDR GVQRKVSGSR GSFCKAGGTL ENADSARRGS CPLEKCNVKA KSNVDLRRSL 
601:	YALCLDTSRE TDL