Potassium voltage-gated channel subfamily A member 5

Function

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. Homotetrameric channels display rapid activation and slow inactivation. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets.

Classification

Family (Pfam)

PF02214 BTB_2, PF00520 Ion_trans

InterPro

BTB/POZ_dom, Ion_trans_dom, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv1, K_chnl_volt-dep_Kv1.5, SKP1/BTB/POZ_sf, T1-type_BTB, VG_K_chnl, Volt_channel_dom_sf

Functional cluster

Eukaryotic Transcription Factors & related

Gene Ontology · 43

• GO:0009986 cell surface
• GO:0005794 Golgi apparatus
• GO:0014704 intercalated disc
• GO:0046691 intracellular canaliculus
• GO:0016020 membrane
• GO:0045121 membrane raft
• GO:0048471 perinuclear region of cytoplasm
• GO:0005886 plasma membrane
• GO:0034705 potassium channel complex
• GO:0008076 voltage-gated potassium channel complex
• GO:0030018 Z disc
• GO:0051393 alpha-actinin binding
• GO:0005251 delayed rectifier potassium channel activity
• GO:0015271 outward rectifier potassium channel activity
• GO:0019901 protein kinase binding
• GO:0097110 scaffold protein binding
• GO:0005102 signaling receptor binding
• GO:0005249 voltage-gated potassium channel activity
• GO:0086089 voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization
• GO:0086087 voltage-gated potassium channel activity involved in bundle of His cell action potential repolarization
• GO:0086090 voltage-gated potassium channel activity involved in SA node cell action potential repolarization
• GO:0001508 action potential
• GO:0086014 atrial cardiac muscle cell action potential
• GO:0060081 membrane hyperpolarization
• GO:0098914 membrane repolarization during atrial cardiac muscle cell action potential
• GO:0086050 membrane repolarization during bundle of His cell action potential
• GO:0086052 membrane repolarization during SA node cell action potential
• GO:0051481 negative regulation of cytosolic calcium ion concentration
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
• GO:2000288 positive regulation of myoblast proliferation
• GO:0097623 potassium ion export across plasma membrane
• GO:0055075 potassium ion homeostasis
• GO:0071805 potassium ion transmembrane transport
• GO:0006813 potassium ion transport
• GO:0051260 protein homooligomerization
• GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization
• GO:0086091 regulation of heart rate by cardiac conduction
• GO:0050796 regulation of insulin secretion
• GO:0042391 regulation of membrane potential
• GO:0042542 response to hydrogen peroxide
• GO:0055093 response to hyperoxia
• GO:0001666 response to hypoxia
• GO:0009612 response to mechanical stimulus

Disease associations

• atrial fibrillation, familial, 7 MONDO:0012828

Drugs targeting this protein · 7

• TEDISAMIL blocker
• GUANIDINE HYDROCHLORIDE blocker
• VERNAKALANT HYDROCHLORIDE blocker
• NERISPIRDINE blocker
• DALFAMPRIDINE blocker
• AMIFAMPRIDINE PHOSPHATE blocker
• AMIFAMPRIDINE blocker

Related proteins · sequence + function similarity

• Potassium voltage-gated channel subfamily A member 5 0.98
• Potassium voltage-gated channel subfamily A member 5 0.98
• Potassium voltage-gated channel subfamily A member 5 0.98
• Potassium voltage-gated channel subfamily A member 5 0.97
• Potassium voltage-gated channel subfamily A member 6 0.92
• Potassium voltage-gated channel subfamily A member 6 0.92
• Potassium voltage-gated channel subfamily A member 6 0.91
• Potassium voltage-gated channel subfamily A member 7 0.89
• Potassium voltage-gated channel subfamily A member 7 0.88
• Potassium voltage-gated channel subfamily A member 3 0.86
• Potassium voltage-gated channel subfamily A member 3 0.85
• Potassium voltage-gated channel subfamily A member 3 0.85

Co-cited proteins · studied together in the literature

• Potassium voltage-gated channel subfamily A member 3 1 shared papers
• Potassium voltage-gated channel subfamily A member 4 1 shared papers
• Voltage-gated potassium channel subunit beta-1 1 shared papers
• Bone morphogenetic protein receptor type-2 1 shared papers
• Activin receptor type-1-like 1 shared papers

Literature · 16 cited papers

• Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension. Am. J. Respir. Cell Mol. Biol. · 2023
• Customized Massive Parallel Sequencing Panel for Diagnosis of Pulmonary Arterial Hypertension. Genes (Basel) · 2020
• Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in patients with pulmonary arterial hypertension. PLoS ONE · 2014
• Tetramerization domain mutations in KCNA5 affect channel kinetics and cause abnormal trafficking patterns. Am. J. Physiol. · 2010
• Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension. Am. J. Physiol. · 2007
• SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5. Proc. Natl. Acad. Sci. U.S.A. · 2007
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum. Mol. Genet. · 2006
• A specific N-terminal residue in Kv1.5 is required for upregulation of the channel by SAP97. Biochem. Biophys. Res. Commun. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Modulation of the human Kv1.5 channel by protein kinase C activation: role of the Kvbeta1.2 subunit. J. Pharmacol. Exp. Ther. · 2002
• Altered state dependence of c-type inactivation in the long and short forms of human Kv1.5. J. Gen. Physiol. · 2001
• … and 4 more in the literature graph