Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Potassium voltage-gated channel subfamily A member 2

Gene

KCNA2

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. 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 (PubMed:8415758). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:8415758). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).By similarity1 Publication

Enzyme regulationi

Inhibited by 4-aminopyridine (4-AP) (PubMed:8415758). Inhibited by dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei252Important for normal, slow channel gatingBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily A member 2
Alternative name(s):
CSMK1
Voltage-gated potassium channel subunit Kv1.2
Gene namesi
Name:KCNA2
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein By similarityCurated
  • Membrane By similarity
  • Cell projectionaxon By similarity
  • Cell junctionsynapse By similarity
  • Cell junctionsynapsepresynaptic cell membrane By similarity
  • Cell junctionsynapsesynaptosome By similarity
  • Endoplasmic reticulum membrane By similarity
  • Cell projectiondendrite By similarity
  • Cell projectionlamellipodium membrane By similarity

  • Note: KCNA2 by itself is detected both at the endoplasmic reticulum and at the cell membrane. Coexpression with KCNA4 or with beta subunits promotes expression at the cell membrane. Coexpression with KCNA1 inhibits cell surface expression.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 160CytoplasmicBy similarityAdd BLAST160
Transmembranei161 – 182Helical; Name=Segment S1By similarityAdd BLAST22
Topological domaini183 – 221ExtracellularBy similarityAdd BLAST39
Transmembranei222 – 243Helical; Name=Segment S2By similarityAdd BLAST22
Topological domaini244 – 254CytoplasmicBy similarityAdd BLAST11
Transmembranei255 – 275Helical; Name=Segment S3By similarityAdd BLAST21
Topological domaini276 – 289ExtracellularBy similarityAdd BLAST14
Transmembranei290 – 310Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST21
Topological domaini311 – 325CytoplasmicBy similarityAdd BLAST15
Transmembranei326 – 347Helical; Name=Segment S5By similarityAdd BLAST22
Topological domaini348 – 361ExtracellularBy similarityAdd BLAST14
Intramembranei362 – 373Helical; Name=Pore helixBy similarityAdd BLAST12
Intramembranei374 – 381By similarity8
Topological domaini382 – 388ExtracellularBy similarity7
Transmembranei389 – 417Helical; Name=Segment S6By similarityAdd BLAST29
Topological domaini418 – 499CytoplasmicBy similarityAdd BLAST82

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Endoplasmic reticulum, Membrane, Synapse, Synaptosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539711 – 499Potassium voltage-gated channel subfamily A member 2Add BLAST499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi207N-linked (GlcNAc...)Sequence analysis1
Lipidationi244S-palmitoyl cysteineSequence analysis1
Modified residuei429PhosphotyrosineBy similarity1
Modified residuei434PhosphoserineBy similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei441PhosphoserineBy similarity1
Modified residuei449PhosphoserineBy similarity1
Modified residuei468PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (By similarity). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on tyrosine residues suppresses ion channel activity (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channel subunits (By similarity). Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (By similarity).By similarity
N-glycosylated, with complex, sialylated N-glycans.By similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ28293.
PRIDEiQ28293.

Expressioni

Tissue specificityi

Expressed in a wide variety of gastrointestinal smooth muscles. Not expressed in portal vein, renal artery, and uterus.1 Publication

Interactioni

Subunit structurei

Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (By similarity). Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Interacts with the beta subunit KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (By similarity). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000029266.

Structurei

3D structure databases

ProteinModelPortaliQ28293.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 125Tetramerization domainBy similarityAdd BLAST125
Regioni312 – 325S4-S5 linkerBy similarityAdd BLAST14

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi374 – 379Selectivity filterBy similarity6
Motifi497 – 499PDZ-bindingBy similarity3

Domaini

The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (By similarity).By similarity
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1545. Eukaryota.
COG1226. LUCA.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ28293.
KOiK04875.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004049. K_chnl_volt-dep_Kv1.2.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01509. KV12CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

Q28293-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTVATGEPAD EAAALPGHPQ DTYDPEADHE CCERVVTNIS GLRFETQLKT
60 70 80 90 100
LAQFPETLLG DPKKRMRFFD PLRNEIFFVR NRPSFDAILY YYQSGGRLRR
110 120 130 140 150
PVNVPLDIFS EEIRFYELGE EAMEMFREDE GYIKEEERPL PENEFQRQVW
160 170 180 190 200
LLFEYPESSG PARIIAIVSV MVILISIVSF CLETLPIFRD ENEDMHGGGV
210 220 230 240 250
TFHTYSNSTI GYQQSTSFTD PFFIVETLCI IWFSFEFLVR FFACPSKAGF
260 270 280 290 300
FTNIMNIIDI VAIIPYFITL GTELAEKPED AQQGQQAMSL AILRVIRLVR
310 320 330 340 350
VFRIFKLSRH SKGLQILGQT LKASMRELGL LIFFLFIGVI LFSSAVYFAE
360 370 380 390 400
ADERESQFPS IPDAFWWAVV SMTTVGYGDM VPTTIGGKIV GSLCAIAGVL
410 420 430 440 450
TIALPVPVIV SNFNYFYHRE TEGEEQAQYL QVTSCPKIPS SPDLKKSRSA
460 470 480 490
STISKSDYME IQEGVNNSNE DFREENLKTA NCTLANTNYV NITKMLTDV
Length:499
Mass (Da):56,607
Last modified:November 1, 1996 - v1
Checksum:i394FDA7D04CA8EC8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19740 mRNA. Translation: AAA03607.1.
PIRiA48672.
RefSeqiNP_001003329.1. NM_001003329.1.
UniGeneiCfa.3898.

Genome annotation databases

GeneIDi404022.
KEGGicfa:404022.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19740 mRNA. Translation: AAA03607.1.
PIRiA48672.
RefSeqiNP_001003329.1. NM_001003329.1.
UniGeneiCfa.3898.

3D structure databases

ProteinModelPortaliQ28293.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000029266.

Proteomic databases

PaxDbiQ28293.
PRIDEiQ28293.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi404022.
KEGGicfa:404022.

Organism-specific databases

CTDi3737.

Phylogenomic databases

eggNOGiKOG1545. Eukaryota.
COG1226. LUCA.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ28293.
KOiK04875.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004049. K_chnl_volt-dep_Kv1.2.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01509. KV12CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNA2_CANLF
AccessioniPrimary (citable) accession number: Q28293
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: November 1, 1996
Last modified: October 5, 2016
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.