KCND2_HUMAN
ID KCND2_HUMAN Reviewed; 630 AA.
AC Q9NZV8; O95012; O95021; Q2TBD3; Q9UBY7; Q9UN98; Q9UNH9;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Potassium voltage-gated channel subfamily D member 2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv4.2;
GN Name=KCND2; Synonyms=KIAA1044;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9843794; DOI=10.1152/ajpheart.1998.275.6.h1963;
RA Kong W., Po S., Yamagishi T., Ashen M.D., Stetten G., Tomaselli G.F.;
RT "Isolation and characterization of the human gene encoding Ito: further
RT diversity by alternative mRNA splicing.";
RL Am. J. Physiol. 275:H1963-H1970(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=10551270;
RA Zhu X.-R., Wulf A., Schwarz M., Isbrandt D., Pongs O.;
RT "Characterization of human Kv4.2 mediating a rapidly-inactivating transient
RT voltage-sensitive K+ current.";
RL Recept. Channels 6:387-400(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain cortex;
RX PubMed=10729221; DOI=10.1006/geno.2000.6117;
RA Isbrandt D., Leicher T., Waldschuetz R., Zhu X.-R., Luhmann U., Michel U.,
RA Sauter K., Pongs O.;
RT "Gene structures and expression profiles of three human KCND (Kv4)
RT potassium channels mediating A-type currents I(TO) and I(SA).";
RL Genomics 64:144-154(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP MUTAGENESIS OF 601-PRO--PRO-604, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP FLNA AND FLNC.
RX PubMed=11102480; DOI=10.1523/jneurosci.20-23-08736.2000;
RA Petrecca K., Miller D.M., Shrier A.;
RT "Localization and enhanced current density of the Kv4.2 potassium channel
RT by interaction with the actin-binding protein filamin.";
RL J. Neurosci. 20:8736-8744(2000).
RN [8]
RP INTERACTION WITH KCNIP1.
RX PubMed=10676964; DOI=10.1038/35000592;
RA An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G.,
RA Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J.;
RT "Modulation of A-type potassium channels by a family of calcium sensors.";
RL Nature 403:553-556(2000).
RN [9]
RP INTERACTION WITH KCNIP2.
RX PubMed=11287421; DOI=10.1074/jbc.m101320200;
RA Baehring R., Dannenberg J., Peters H.C., Leicher T., Pongs O., Isbrandt D.;
RT "Conserved Kv4 N-terminal domain critical for effects of Kv channel-
RT interacting protein 2.2 on channel expression and gating.";
RL J. Biol. Chem. 276:23888-23894(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND DOMAIN.
RX PubMed=11507158; DOI=10.1111/j.1469-7793.2001.00065.x;
RA Baehring R., Boland L.M., Varghese A., Gebauer M., Pongs O.;
RT "Kinetic analysis of open- and closed-state inactivation transitions in
RT human Kv4.2 A-type potassium channels.";
RL J. Physiol. (Lond.) 535:65-81(2001).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=12395204; DOI=10.1007/s00395-002-0377-4;
RA Bertaso F., Sharpe C.C., Hendry B.M., James A.F.;
RT "Expression of voltage-gated K+ channels in human atrium.";
RL Basic Res. Cardiol. 97:424-433(2002).
RN [12]
RP INTERACTION WITH KCNIP4.
RX PubMed=11847232; DOI=10.1074/jbc.m200897200;
RA Morohashi Y., Hatano N., Ohya S., Takikawa R., Watabiki T., Takasugi N.,
RA Imaizumi Y., Tomita T., Iwatsubo T.;
RT "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand
RT protein interacting with presenilin 2 and voltage-gated potassium channel
RT subunit Kv4.";
RL J. Biol. Chem. 277:14965-14975(2002).
RN [13]
RP INTERACTION WITH KCNIP3.
RX PubMed=12451113; DOI=10.1523/jneurosci.22-23-10123.2002;
RA Schrader L.A., Anderson A.E., Mayne A., Pfaffinger P.J., Sweatt J.D.;
RT "PKA modulation of Kv4.2-encoded A-type potassium channels requires
RT formation of a supramolecular complex.";
RL J. Neurosci. 22:10123-10133(2002).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=14695263; DOI=10.1016/s0006-3495(04)74097-7;
RA Gebauer M., Isbrandt D., Sauter K., Callsen B., Nolting A., Pongs O.,
RA Baehring R.;
RT "N-type inactivation features of Kv4.2 channel gating.";
RL Biophys. J. 86:210-223(2004).
RN [15]
RP FUNCTION, INTERACTION WITH DPP10 AND DPP6, AND SUBCELLULAR LOCATION.
RX PubMed=15454437; DOI=10.1529/biophysj.104.042358;
RA Jerng H.H., Qian Y., Pfaffinger P.J.;
RT "Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase
RT 10 (DPP10).";
RL Biophys. J. 87:2380-2396(2004).
RN [16]
RP INTERACTION WITH KCNIP1 AND KCNIP2, SUBUNIT, AND DOMAIN.
RX PubMed=15358149; DOI=10.1016/j.bbrc.2004.07.006;
RA Lin Y.-L., Chen C.Y., Cheng C.P., Chang L.S.;
RT "Protein-protein interactions of KChIP proteins and Kv4.2.";
RL Biochem. Biophys. Res. Commun. 321:606-610(2004).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, AND ROLE IN DISEASE.
RX PubMed=16934482; DOI=10.1016/j.nbd.2006.07.001;
RA Singh B., Ogiwara I., Kaneda M., Tokonami N., Mazaki E., Baba K.,
RA Matsuda K., Inoue Y., Yamakawa K.;
RT "A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.";
RL Neurobiol. Dis. 24:245-253(2006).
RN [18]
RP REVIEW.
RX PubMed=17917103; DOI=10.1007/s12035-007-8001-0;
RA Baranauskas G.;
RT "Ionic channel function in action potential generation: current
RT perspective.";
RL Mol. Neurobiol. 35:129-150(2007).
RN [19]
RP REVIEW.
RX PubMed=18357523; DOI=10.1007/s11064-008-9650-8;
RA Covarrubias M., Bhattacharji A., De Santiago-Castillo J.A., Dougherty K.,
RA Kaulin Y.A., Na-Phuket T.R., Wang G.;
RT "The neuronal Kv4 channel complex.";
RL Neurochem. Res. 33:1558-1567(2008).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF GLY-309;
RP ARG-311; ILE-312; LEU-313; GLY-314; TYR-315; THR-316; LEU-317; LYS-318;
RP SER-319; CYS-320; SER-322; GLU-323; LEU-324; LEU-327; LEU-328; VAL-397;
RP ILE-398; ALA-399; PRO-401; 402-VAL--VAL-404; PRO-403; ILE-405; VAL-406;
RP SER-407; ASN-408 AND PHE-409.
RX PubMed=19171772; DOI=10.1085/jgp.200810073;
RA Barghaan J., Baehring R.;
RT "Dynamic coupling of voltage sensor and gate involved in closed-state
RT inactivation of Kv4.2 channels.";
RL J. Gen. Physiol. 133:205-224(2009).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH KCNIP4.
RX PubMed=24811166; DOI=10.1074/jbc.m114.563452;
RA Kitazawa M., Kubo Y., Nakajo K.;
RT "The stoichiometry and biophysical properties of the Kv4 potassium channel
RT complex with K+ channel-interacting protein (KChIP) subunits are variable,
RT depending on the relative expression level.";
RL J. Biol. Chem. 289:17597-17609(2014).
RN [22]
RP STRUCTURE BY ELECTRON MICROSCOPY (21 ANGSTROMS) OF THE KCND2-KCNIP2
RP COMPLEX, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=14980201; DOI=10.1016/s0896-6273(04)00050-9;
RA Kim L.A., Furst J., Gutierrez D., Butler M.H., Xu S., Goldstein S.A.,
RA Grigorieff N.;
RT "Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by
RT electron microscopy at 21 Angstrom resolution.";
RL Neuron 41:513-519(2004).
RN [23]
RP INTERACTION WITH KCNIP2, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=14623880; DOI=10.1074/jbc.m311332200;
RA Kim L.A., Furst J., Butler M.H., Xu S., Grigorieff N., Goldstein S.A.;
RT "Ito channels are octameric complexes with four subunits of each Kv4.2 and
RT K+ channel-interacting protein 2.";
RL J. Biol. Chem. 279:5549-5554(2004).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=15991246; DOI=10.1002/jcp.20453;
RA Kunz L., Ramsch R., Krieger A., Young K.A., Dissen G.A., Stouffer R.L.,
RA Ojeda S.R., Mayerhofer A.;
RT "Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells
RT of the human ovary.";
RL J. Cell. Physiol. 206:167-174(2006).
RN [25]
RP INTERACTION WITH KCNIP1.
RX PubMed=14980207; DOI=10.1016/s0896-6273(04)00049-2;
RA Scannevin R.H., Wang K., Jow F., Megules J., Kopsco D.C., Edris W.,
RA Carroll K.C., Lu Q., Xu W., Xu Z., Katz A.H., Olland S., Lin L., Taylor M.,
RA Stahl M., Malakian K., Somers W., Mosyak L., Bowlby M.R., Chanda P.,
RA Rhodes K.J.;
RT "Two N-terminal domains of Kv4 K(+) channels regulate binding to and
RT modulation by KChIP1.";
RL Neuron 41:587-598(2004).
RN [26]
RP INTERACTION WITH DLG1.
RX PubMed=19213956; DOI=10.1161/circresaha.108.191007;
RA El-Haou S., Balse E., Neyroud N., Dilanian G., Gavillet B., Abriel H.,
RA Coulombe A., Jeromin A., Hatem S.N.;
RT "Kv4 potassium channels form a tripartite complex with the anchoring
RT protein SAP97 and CaMKII in cardiac myocytes.";
RL Circ. Res. 104:758-769(2009).
RN [27]
RP VARIANT MET-404, CHARACTERIZATION OF VARIANT MET-404, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24501278; DOI=10.1093/hmg/ddu056;
RA Lee H., Lin M.C., Kornblum H.I., Papazian D.M., Nelson S.F.;
RT "Exome sequencing identifies de novo gain of function missense mutation in
RT KCND2 in identical twins with autism and seizures that slows potassium
RT channel inactivation.";
RL Hum. Mol. Genet. 23:3481-3489(2014).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes, primarily in the brain.
CC Mediates the major part of the dendritic A-type current I(SA) in brain
CC neurons (By similarity). This current is activated at membrane
CC potentials that are below the threshold for action potentials. It
CC regulates neuronal excitability, prolongs the latency before the first
CC spike in a series of action potentials, regulates the frequency of
CC repetitive action potential firing, shortens the duration of action
CC potentials and regulates the back-propagation of action potentials from
CC the neuronal cell body to the dendrites. Contributes to the regulation
CC of the circadian rhythm of action potential firing in suprachiasmatic
CC nucleus neurons, which regulates the circadian rhythm of locomotor
CC activity (By similarity). Functions downstream of the metabotropic
CC glutamate receptor GRM5 and plays a role in neuronal excitability and
CC in nociception mediated by activation of GRM5 (By similarity). Mediates
CC the transient outward current I(to) in rodent heart left ventricle apex
CC cells, but not in human heart, where this current is mediated by
CC another family member. Forms tetrameric potassium-selective channels
CC through which potassium ions pass in accordance with their
CC electrochemical gradient (PubMed:10551270, PubMed:15454437,
CC PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482,
CC PubMed:24811166, PubMed:24501278). The channel alternates between
CC opened and closed conformations in response to the voltage difference
CC across the membrane (PubMed:11507158). Can form functional
CC homotetrameric channels and heterotetrameric channels that contain
CC variable proportions of KCND2 and KCND3; channel properties depend on
CC the type of pore-forming alpha subunits that are part of the channel.
CC In vivo, membranes probably contain a mixture of heteromeric potassium
CC channel complexes. Interaction with specific isoforms of the regulatory
CC subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression
CC at the cell surface and thereby increases channel activity; it
CC modulates the kinetics of channel activation and inactivation, shifts
CC the threshold for channel activation to more negative voltage values,
CC shifts the threshold for inactivation to less negative voltages and
CC accelerates recovery after inactivation (PubMed:15454437,
CC PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278,
CC PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes
CC expression at the cell membrane and regulates both channel
CC characteristics and activity (By similarity).
CC {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2,
CC ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221,
CC ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880,
CC ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201,
CC ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482,
CC ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278,
CC ECO:0000269|PubMed:24811166}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Homotetrameric channels activate rapidly, i.e within a few msec.
CC After that, they inactivate rapidly, i.e within about 50-100 msec.
CC The voltage-dependence of activation and inactivation and other
CC channel characteristics vary depending on the experimental
CC conditions, the expression system and the presence or absence of
CC ancillary subunits. Homotetrameric channels have a unitary
CC conductance of about 4 pS when expressed in a heterologous system.
CC For the activation of homotetrameric channels expressed in xenopus
CC oocytes, the voltage at half-maximal amplitude is about -10 mV. The
CC time constant for inactivation is about 20 msec. For inactivation,
CC the voltage at half-maximal amplitude is -62 mV. The time constant
CC for recovery after inactivation is about 70 msec.
CC {ECO:0000305|PubMed:11507158, ECO:0000305|PubMed:17917103};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCND1 or KCND3
CC (PubMed:14980201, PubMed:16934482, PubMed:24811166). Associates with
CC the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4
CC (PubMed:10676964, PubMed:11287421, PubMed:11847232, PubMed:12451113,
CC PubMed:15358149, PubMed:14623880, PubMed:14980201, PubMed:14980207,
CC PubMed:24811166). In vivo, probably exists as heteromeric complex
CC containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2,
CC KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19171772). The tetrameric
CC channel can associate with up to four regulatory subunits, such as
CC KCNIP2 or KCNIP4 (PubMed:14623880, PubMed:14980201, PubMed:24811166).
CC Interaction with four KCNIP4 chains does not reduce interaction with
CC DPP10 (PubMed:24811166). Interacts with DLG4 and NCS1/FREQ (By
CC similarity). Interacts with DLG1 (PubMed:19213956). Probably part of a
CC complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2
CC (PubMed:15358149). Interacts with FLNA, FLNC, DPP6 and DPP10
CC (PubMed:11102480, PubMed:15454437, PubMed:24811166).
CC {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2,
CC ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11102480,
CC ECO:0000269|PubMed:11287421, ECO:0000269|PubMed:11847232,
CC ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:14623880,
CC ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:14980207,
CC ECO:0000269|PubMed:15358149, ECO:0000269|PubMed:15454437,
CC ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19213956,
CC ECO:0000269|PubMed:24811166, ECO:0000305|PubMed:19171772}.
CC -!- INTERACTION:
CC Q9NZV8; Q9NZI2: KCNIP1; NbExp=4; IntAct=EBI-1646745, EBI-2120635;
CC Q9NZV8; Q9NS61: KCNIP2; NbExp=3; IntAct=EBI-1646745, EBI-1052975;
CC Q9NZV8; Q9NS61-3: KCNIP2; NbExp=3; IntAct=EBI-1646745, EBI-1053010;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11102480,
CC ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880,
CC ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201,
CC ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482,
CC ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278,
CC ECO:0000269|PubMed:24811166}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:14980201,
CC ECO:0000305}. Cell projection, dendrite {ECO:0000269|PubMed:11102480}.
CC Synapse {ECO:0000250|UniProtKB:Q63881}. Perikaryon
CC {ECO:0000250|UniProtKB:Q63881}. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q63881}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q63881}. Cell junction
CC {ECO:0000250|UniProtKB:Q63881}. Note=In neurons, primarily detected on
CC dendrites, dendritic spines and on the neuron cell body, but not on
CC axons. Localized preferentially at the dendrites of pyramidal cells in
CC the hippocampus CA1 layer. Detected at GABAergic synapses. Detected at
CC cell junctions that are distinct from synaptic cell contacts. Detected
CC in lipid rafts. Detected primarily at the endoplasmic reticulum or
CC Golgi when expressed by itself (PubMed:15454437). Interaction with
CC KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression at the cell
CC membrane (PubMed:15454437, PubMed:24811166). Interaction with DPP6 or
CC DPP10 promotes expression at the cell membrane (By similarity).
CC Internalized from the cell membrane by clathrin-dependent endocytosis
CC in response to activation of AMPA-selective glutamate receptors and
CC PKA-mediated phosphorylation at Ser-552. Redistributed from dendritic
CC spines to the main dendritic shaft in response to activation of AMPA-
CC selective glutamate receptors and activation of PKA (By similarity).
CC {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2,
CC ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:24811166}.
CC -!- TISSUE SPECIFICITY: Detected in ovary, in corpus luteum and in
CC granulosa and theca cells in the follicle (at protein level)
CC (PubMed:15991246). Highly expressed throughout the brain
CC (PubMed:10551270, PubMed:10729221). Detected in amygdala, caudate
CC nucleus, cerebellum, hippocampus, substantia nigra and thalamus
CC (PubMed:10551270, PubMed:10729221). Expression is not detectable or
CC very low in heart, kidney, liver, lung, pancreas and skeletal muscle
CC (PubMed:10551270, PubMed:10729221). Not detectable in human heart
CC atrium (PubMed:12395204). {ECO:0000269|PubMed:10551270,
CC ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:12395204,
CC ECO:0000269|PubMed:15991246}.
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 -!- DOMAIN: The N-terminal cytoplasmic region can mediate N-type
CC inactivation by physically blocking the channel (PubMed:14695263). This
CC probably does not happen in vivo, where the N-terminal region mediates
CC interaction with regulatory subunits, such as KCNIP1 and KCNIP2
CC (PubMed:15358149). The zinc binding sites in the N-terminal domain are
CC important for tetramerization and assembly of a functional channel
CC complex (By similarity). Most likely, the channel undergoes closed-
CC state inactivation, where a subtle conformation change would render the
CC protein less sensitive to activation. {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000305|PubMed:11507158, ECO:0000305|PubMed:14695263,
CC ECO:0000305|PubMed:15358149, ECO:0000305|PubMed:18357523}.
CC -!- DOMAIN: The C-terminal cytoplasmic region is important for normal
CC expression at the cell membrane and modulates the voltage-dependence of
CC channel activation and inactivation (PubMed:16934482). It is required
CC for interaction with KCNIP2, and probably other family members as well
CC (By similarity). {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000269|PubMed:16934482}.
CC -!- PTM: Phosphorylation at Ser-438 in response to MAPK activation is
CC increased in stimulated dendrites. Interaction with KCNIP2 and DPP6
CC propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552
CC has no effect on interaction with KCNIP3, but is required for the
CC regulation of channel activity by KCNIP3. Phosphorylation at Ser-552
CC leads to KCND2 internalization (By similarity). Phosphorylated by MAPK
CC in response to signaling via the metabotropic glutamate receptor GRM5
CC (By similarity). Phosphorylation at Ser-616 is required for the down-
CC regulation of neuronal A-type currents in response to signaling via
CC GRM5 (By similarity). {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000250|UniProtKB:Q9Z0V2}.
CC -!- DISEASE: Note=KNCD2 mutations have been found in a family with autism
CC and epilepsy and may play a role in disease pathogenesis. Autism is a
CC complex multifactorial, pervasive developmental disorder characterized
CC by impairments in reciprocal social interaction and communication,
CC restricted and stereotyped patterns of interests and activities, and
CC the presence of developmental abnormalities by 3 years of age. Epilepsy
CC is characterized by paroxysmal transient disturbances of the electrical
CC activity of the brain that may be manifested as episodic impairment or
CC loss of consciousness, abnormal motor phenomena, psychic or sensory
CC disturbances, or perturbation of the autonomic nervous system.
CC {ECO:0000269|PubMed:24501278}.
CC -!- DISEASE: Note=A KCND2 mutation leading to the production of a C-
CC terminally truncated protein has been identified in a patient with
CC epilepsy. Epilepsy is characterized by paroxysmal transient
CC disturbances of the electrical activity of the brain that may be
CC manifested as episodic impairment or loss of consciousness, abnormal
CC motor phenomena, psychic or sensory disturbances, or perturbation of
CC the autonomic nervous system. {ECO:0000269|PubMed:16934482}.
CC -!- MISCELLANEOUS: The transient neuronal A-type potassium current called
CC I(SA) is triggered at membrane potentials that are below the threshold
CC for action potentials. It inactivates rapidly and recovers rapidly from
CC inactivation. It regulates the firing of action potentials and plays a
CC role in synaptic integration and plasticity. Potassium channels
CC containing KCND2 account for about 80% of the neuronal A-type potassium
CC current. In contrast, the potassium channel responsible for the cardiac
CC I(to) current differs between species; it is mediated by KCND2 in
CC rodents. In human and other non-rodents KCND3 may play an equivalent
CC role. {ECO:0000269|PubMed:10551270, ECO:0000305|PubMed:17917103,
CC ECO:0000305|PubMed:18357523}.
CC -!- MISCELLANEOUS: Is specifically and reversibly inhibited by the scorpion
CC toxin Ts8 (AC P69940). {ECO:0000250|UniProtKB:Q63881}.
CC -!- SIMILARITY: Belongs to the potassium channel family. D (Shal) (TC
CC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA82996.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF121104; AAD22053.1; -; mRNA.
DR EMBL; AB028967; BAA82996.2; ALT_INIT; mRNA.
DR EMBL; AJ010969; CAB56841.1; -; mRNA.
DR EMBL; AF166008; AAF65618.1; -; Genomic_DNA.
DR EMBL; AF166007; AAF65618.1; JOINED; Genomic_DNA.
DR EMBL; AC004888; AAC83405.1; -; Genomic_DNA.
DR EMBL; AC004946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF142568; AAD52159.1; -; Genomic_DNA.
DR EMBL; BC110449; AAI10450.1; -; mRNA.
DR EMBL; BC110450; AAI10451.1; -; mRNA.
DR CCDS; CCDS5776.1; -.
DR RefSeq; NP_036413.1; NM_012281.2.
DR PDB; 7E7Z; EM; 3.20 A; A/B/C/D=163-417.
DR PDB; 7E83; EM; 3.10 A; A/C/D/G=2-495.
DR PDB; 7E87; EM; 3.40 A; A/D=40-436, B/C=40-437.
DR PDB; 7E8B; EM; 4.20 A; A/C=40-436, B/D=40-437.
DR PDB; 7E8E; EM; 3.90 A; A/B/C/D=2-495.
DR PDB; 7E8H; EM; 4.50 A; A/B/C/D=2-495.
DR PDB; 7F0J; EM; 2.90 A; B/C/F/H=1-630.
DR PDB; 7F3F; EM; 3.10 A; A/B/D/G=1-630.
DR PDBsum; 7E7Z; -.
DR PDBsum; 7E83; -.
DR PDBsum; 7E87; -.
DR PDBsum; 7E8B; -.
DR PDBsum; 7E8E; -.
DR PDBsum; 7E8H; -.
DR PDBsum; 7F0J; -.
DR PDBsum; 7F3F; -.
DR AlphaFoldDB; Q9NZV8; -.
DR SMR; Q9NZV8; -.
DR BioGRID; 109953; 20.
DR ComplexPortal; CPX-3239; Kv4.2-KChIP2 channel complex.
DR CORUM; Q9NZV8; -.
DR IntAct; Q9NZV8; 10.
DR STRING; 9606.ENSP00000333496; -.
DR ChEMBL; CHEMBL5885; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q9NZV8; -.
DR TCDB; 1.A.1.2.5; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q9NZV8; -.
DR PhosphoSitePlus; Q9NZV8; -.
DR BioMuta; KCND2; -.
DR DMDM; 38258257; -.
DR EPD; Q9NZV8; -.
DR MassIVE; Q9NZV8; -.
DR PaxDb; Q9NZV8; -.
DR PeptideAtlas; Q9NZV8; -.
DR PRIDE; Q9NZV8; -.
DR ProteomicsDB; 83521; -.
DR ABCD; Q9NZV8; 1 sequenced antibody.
DR Antibodypedia; 31683; 439 antibodies from 39 providers.
DR DNASU; 3751; -.
DR Ensembl; ENST00000331113.9; ENSP00000333496.4; ENSG00000184408.10.
DR GeneID; 3751; -.
DR KEGG; hsa:3751; -.
DR MANE-Select; ENST00000331113.9; ENSP00000333496.4; NM_012281.3; NP_036413.1.
DR UCSC; uc003vjj.2; human.
DR CTD; 3751; -.
DR DisGeNET; 3751; -.
DR GeneCards; KCND2; -.
DR GeneReviews; KCND2; -.
DR HGNC; HGNC:6238; KCND2.
DR HPA; ENSG00000184408; Tissue enriched (brain).
DR MalaCards; KCND2; -.
DR MIM; 605410; gene.
DR neXtProt; NX_Q9NZV8; -.
DR OpenTargets; ENSG00000184408; -.
DR PharmGKB; PA30030; -.
DR VEuPathDB; HostDB:ENSG00000184408; -.
DR eggNOG; KOG4390; Eukaryota.
DR GeneTree; ENSGT00940000155472; -.
DR HOGENOM; CLU_011722_9_1_1; -.
DR InParanoid; Q9NZV8; -.
DR OMA; RTTVEKY; -.
DR OrthoDB; 469107at2759; -.
DR PhylomeDB; Q9NZV8; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q9NZV8; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR Reactome; R-HSA-5576894; Phase 1 - inactivation of fast Na+ channels.
DR SignaLink; Q9NZV8; -.
DR SIGNOR; Q9NZV8; -.
DR BioGRID-ORCS; 3751; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; KCND2; human.
DR GeneWiki; KCND2; -.
DR GenomeRNAi; 3751; -.
DR Pharos; Q9NZV8; Tclin.
DR PRO; PR:Q9NZV8; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NZV8; protein.
DR Bgee; ENSG00000184408; Expressed in cerebellar vermis and 133 other tissues.
DR ExpressionAtlas; Q9NZV8; baseline and differential.
DR Genevisible; Q9NZV8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0044853; C:plasma membrane raft; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005250; F:A-type (transient outward) potassium channel activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0001508; P:action potential; TAS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:UniProtKB.
DR GO; GO:0045475; P:locomotor rhythm; IEA:Ensembl.
DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
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; IPR003975; K_chnl_volt-dep_Kv4.
DR InterPro; IPR004055; K_chnl_volt-dep_Kv4.2.
DR InterPro; IPR024587; K_chnl_volt-dep_Kv4_C.
DR InterPro; IPR021645; Shal-type_N.
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 Pfam; PF02214; BTB_2; 1.
DR Pfam; PF11879; DUF3399; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF11601; Shal-type; 1.
DR PRINTS; PR01517; KV42CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01497; SHALCHANNEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autism; Autism spectrum disorder; Cell junction;
KW Cell membrane; Cell projection; Disease variant; Epilepsy; Ion channel;
KW Ion transport; Membrane; Metal-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel; Zinc.
FT CHAIN 1..630
FT /note="Potassium voltage-gated channel subfamily D member
FT 2"
FT /id="PRO_0000054064"
FT TOPO_DOM 1..182
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 183..204
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 205..228
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 229..250
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 251..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 262..279
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 280..286
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 287..306
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 307..321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 322..343
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 344..357
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 358..369
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 370..377
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 378..384
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 385..413
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 414..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 2..20
FT /note="Interaction with KCNIP1, KCNIP2, and other family
FT members"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT REGION 71..90
FT /note="Interaction with KCNIP1"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT REGION 308..321
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 474..630
FT /note="Important for normal channel activation and
FT inactivation, for interaction with KCNIP2, and probably
FT other family members as well"
FT /evidence="ECO:0000250|UniProtKB:Q63881,
FT ECO:0000305|PubMed:16934482"
FT REGION 474..489
FT /note="Required for dendritic targeting"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT REGION 600..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 370..375
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 627..630
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V2"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V2"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V2"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V2"
FT VARIANT 404
FT /note="V -> M (probable disease-associated variant found in
FT a family with atypical autism and severe epilepsy; disrupts
FT potassium current inactivation; dbSNP:rs587777631)"
FT /evidence="ECO:0000269|PubMed:24501278"
FT /id="VAR_072076"
FT MUTAGEN 309
FT /note="G->A: Increases peak current amplitude and causes a
FT negative shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 311
FT /note="R->A: No effect on peak current amplitude, but
FT causes a positive shift in the voltage-dependence of
FT activation. May increase the affinity for the closed-
FT inactivated state of the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 312
FT /note="I->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 313
FT /note="L->A: Causes a positive shift in the voltage-
FT dependence of activation. May decrease the affinity for the
FT closed-inactivated state of the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 314
FT /note="G->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 315
FT /note="Y->A: Increases peak current amplitude but has a
FT minor effect on the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 316
FT /note="T->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 317
FT /note="L->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 318
FT /note="K->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 319
FT /note="S->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 320
FT /note="C->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 320
FT /note="C->S: Increases peak current amplitude and slows the
FT onset of inactivation at low voltage, but has no effect on
FT the voltage-dependence of activation."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 322
FT /note="S->A: Increases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation. May
FT increase the affinity for the closed-inactivated state of
FT the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 323
FT /note="E->A: Slightly increases peak current amplitude and
FT causes a negative shift in the voltage-dependence of
FT activation. May decrease the affinity for the closed-
FT inactivated state of the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 324
FT /note="L->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 327
FT /note="L->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 328
FT /note="L->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 329
FT /note="F->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 397
FT /note="V->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 398
FT /note="I->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 399
FT /note="A->V: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 401
FT /note="P->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 402..404
FT /note="VPV->IPI: Increases pak current amplitude and causes
FT a positive shift in the voltage-dependence of activation
FT and steady-state inactivation. May increase the affinity
FT for the closed-inactivated state of the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 403
FT /note="P->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 405
FT /note="I->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 406
FT /note="V->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 407
FT /note="S->A: Increases peak current amplitude but has no
FT effect on the voltage-dependence of activation. May
FT increase the affinity for the closed-inactivated state of
FT the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 408
FT /note="N->A: Decreases peak current amplitude and causes a
FT positive shift in the voltage-dependence of activation. May
FT increase the affinity for the closed-inactivated state of
FT the channel."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 409
FT /note="F->A: May impair protein folding."
FT /evidence="ECO:0000269|PubMed:19171772"
FT MUTAGEN 601..604
FT /note="PTPP->ATAA: Abolishes interaction with FLNC."
FT /evidence="ECO:0000269|PubMed:11102480"
FT CONFLICT 450
FT /note="N -> S (in Ref. 1; AAD22053)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="Q -> P (in Ref. 1; AAD22053)"
FT /evidence="ECO:0000305"
FT CONFLICT 550
FT /note="Q -> R (in Ref. 1; AAD22053)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="I -> V (in Ref. 1; AAD22053)"
FT /evidence="ECO:0000305"
FT HELIX 9..15
FT /evidence="ECO:0007829|PDB:7E83"
FT HELIX 16..19
FT /evidence="ECO:0007829|PDB:7E83"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:7E83"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:7F0J"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:7E87"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:7E83"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:7E83"
FT HELIX 89..100
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:7F3F"
FT HELIX 134..154
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 168..174
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:7F3F"
FT HELIX 183..204
FT /evidence="ECO:0007829|PDB:7F0J"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:7F0J"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:7F3F"
FT HELIX 227..250
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 254..259
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 261..279
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 288..295
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 296..304
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 308..319
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 321..346
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 357..368
FT /evidence="ECO:0007829|PDB:7F0J"
FT STRAND 374..376
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 381..399
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 402..434
FT /evidence="ECO:0007829|PDB:7F0J"
FT HELIX 473..487
FT /evidence="ECO:0007829|PDB:7E83"
FT TURN 488..490
FT /evidence="ECO:0007829|PDB:7E83"
SQ SEQUENCE 630 AA; 70537 MW; 0C11E62FFA220421 CRC64;
MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE
RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA
FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDTAGES ALPTMTARQR VWRAFENPHT
STMALVFYYV TGFFIAVSVI ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF
TVEYLLRLAA APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI
FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS ASKFTSIPAA
FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL PVPVIVSNFS RIYHQNQRAD
KRRAQKKARL ARIRAAKSGS ANAYMQSKRN GLLSNQLQSS EDEQAFVSKS GSSFETQHHH
LLHCLEKTTN HEFVDEQVFE ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKTFRI
PNANVSGSHQ GSIQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
