KCNA2_XENLA
ID KCNA2_XENLA Reviewed; 499 AA.
AC P22739;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 2.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.2;
DE AltName: Full=xSHA2;
GN Name=kcna2;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2223094; DOI=10.1016/0896-6273(90)90223-3;
RA Ribera A.B.;
RT "A potassium channel gene is expressed at neural induction.";
RL Neuron 5:691-701(1990).
RN [2]
RP MUTAGENESIS OF ILE-263; ARG-297; LEU-298 AND PRO-405.
RX PubMed=25751627; DOI=10.1038/ng.3239;
RA Syrbe S., Hedrich U.B., Riesch E., Djemie T., Mueller S., Moeller R.S.,
RA Maher B., Hernandez-Hernandez L., Synofzik M., Caglayan H.S., Arslan M.,
RA Serratosa J.M., Nothnagel M., May P., Krause R., Loeffler H., Detert K.,
RA Dorn T., Vogt H., Kraemer G., Schoels L., Mullis P.E., Linnankivi T.,
RA Lehesjoki A.E., Sterbova K., Craiu D.C., Hoffman-Zacharska D., Korff C.M.,
RA Weber Y.G., Steinlin M., Gallati S., Bertsche A., Bernhard M.K.,
RA Merkenschlager A., Kiess W., Gonzalez M., Zuechner S., Palotie A., Suls A.,
RA De Jonghe P., Helbig I., Biskup S., Wolff M., Maljevic S., Schuele R.,
RA Sisodiya S.M., Weckhuysen S., Lerche H., Lemke J.R.;
RT "De novo loss- or gain-of-function mutations in KCNA2 cause epileptic
RT encephalopathy.";
RL Nat. Genet. 47:393-399(2015).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes, primarily in the brain and
CC central nervous system. Prevents aberrant action potential firing and
CC regulates neuronal output. Forms tetrameric potassium-selective
CC channels through which potassium ions pass in accordance with their
CC electrochemical gradient. The channel alternates between opened and
CC closed conformations in response to the voltage difference across the
CC membrane (PubMed:2223094). Can form functional homotetrameric channels
CC and heterotetrameric channels with other family members; the channels
CC characteristics depend critically on the types of channel-forming alpha
CC subunits that are present (By similarity). Channel properties are
CC modulated by cytoplasmic beta subunits that regulate the subcellular
CC location of the alpha subunits (By similarity). In vivo, membranes
CC probably contain a mixture of heteromeric potassium channel complexes,
CC making it difficult to assign currents observed in intact tissues to
CC any particular potassium channel family member. Homotetrameric KCNA2
CC forms a delayed-rectifier potassium channel that opens in response to
CC membrane depolarization, followed by slow spontaneous channel closure
CC (PubMed:2223094). Regulates neuronal excitability and plays a role as
CC pacemaker in the regulation of neuronal action potentials (By
CC similarity). KCNA2-containing channels play a presynaptic role and
CC prevent hyperexcitability and aberrant action potential firing (By
CC similarity). Response to toxins that are selective for KCNA2-containing
CC potassium channels suggests that in Purkinje cells, dendritic
CC subthreshold KCNA2-containing potassium channels prevent random
CC spontaneous calcium spikes, suppressing dendritic hyperexcitability
CC without hindering the generation of somatic action potentials, and
CC thereby play an important role in motor coordination (By similarity).
CC Plays a role in the induction of long-term potentiation of neuron
CC excitability in the CA3 layer of the hippocampus (By similarity).
CC {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:P63142,
CC ECO:0000269|PubMed:2223094}.
CC -!- SUBUNIT: Homotetramer and heterotetramer with other family members.
CC {ECO:0000250|UniProtKB:P63142}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2223094};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in tadpole brain and spinal cord.
CC {ECO:0000269|PubMed:2223094}.
CC -!- DOMAIN: The cytoplasmic N-terminus is important for tetramerization.
CC Interactions between the different subunits modulate the gating
CC characteristics (By similarity). {ECO:0000250|UniProtKB:P63142}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) (TC
CC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M35664; AAA49933.1; -; Genomic_DNA.
DR PIR; JH0313; JH0313.
DR AlphaFoldDB; P22739; -.
DR SMR; P22739; -.
DR PRIDE; P22739; -.
DR ABCD; P22739; 1 sequenced antibody.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003972; K_chnl_volt-dep_Kv1.
DR InterPro; IPR004049; K_chnl_volt-dep_Kv1.2.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF23; PTHR11537:SF23; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01509; KV12CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01496; SHAKERCHANEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Ion channel; Ion transport; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..499
FT /note="Potassium voltage-gated channel subfamily A member
FT 2"
FT /id="PRO_0000053976"
FT TOPO_DOM 1..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 161..182
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 183..221
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 222..243
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 244..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 255..275
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 276..289
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 290..310
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 311..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 326..347
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 348..361
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 362..373
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 374..381
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 382..388
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 389..417
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 418..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..125
FT /note="Tetramerization domain"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..325
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 374..379
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 497..499
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT SITE 252
FT /note="Important for normal, slow channel gating"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT SITE 381
FT /note="Important for binding with the scorpion
FT mesomartoxin; when the scorpion mesomartoxin-rKv1.2/KCNA2
FT interaction is modeled, this residue is close to the 'Y-57'
FT residue of the toxin"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT LIPID 244
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 263
FT /note="I->T: Causes a dramatic reduction in current
FT amplitude in a dominant-negative manner. Loss of channel
FT function. Causes a depolarizing shift in voltage-dependent
FT activation."
FT MUTAGEN 297
FT /note="R->Q: Causes a gain of function with increased
FT current amplitude and negative shifting of the voltage
FT dependence of activation by -40 mV resulting in permanent
FT opening of the channel. The effect is dominant on the wild-
FT type protein."
FT MUTAGEN 298
FT /note="L->F: Causes a gain of function with increased
FT current amplitude and negative shifting of the voltage
FT dependence of activation by -50 mV resulting in permanent
FT opening of the channel. The effect is dominant on the wild-
FT type protein."
FT MUTAGEN 405
FT /note="P->L: Causes a dramatic reduction in current
FT amplitude in a dominant-negative manner. Loss of channel
FT function."
SQ SEQUENCE 499 AA; 56702 MW; 111415768038DCBB CRC64;
MTVATGDLTD GSVGFAGHPQ DSYDPEPDHE CCERVVINIS GLRFETQLKT LSQFPETLLG
DPKKRMRYFD PLRNEYFFDR NRPSFDAILY FYQSGGRLRR PVNVPLDIFS EEIRFYELGE
EAMEIFREDE GFIKEEERPL PDNEFQKQVW LLFEYPESSG PARIIAIISV TVILISIVSF
CLETLPVFRD ENEDMHGSGG NYYSYPNSTV RFQKSNTFTD PFFIVETLCI IWFSFEFLVR
FLACPSKAVF FTNLMNIIDI VAIIPYFITL GTELAEKTED GQQGQQAMSL AILRVIRLVR
VFRIFKLSRH SKGLQILGQT LNASMRELGL LIFFLFIGVI LFSSAVFFAE ADERDSQFPS
IPDAFWWAVV SMTTVGYGDM VPTTIGGKIV GSLCAIAGVL TIALPVPVIV SNFNYFYHRE
TEGEEQAQYL QVTSCPKIPS SPDLQKSRSA STLSKSDYME IQEGVNHSNE DFREKNLKTA
NCTLGNTNYV NITKMLTDV
