KCND3_HUMAN
ID KCND3_HUMAN Reviewed; 655 AA.
AC Q9UK17; O60576; O60577; Q14D71; Q5T0M0; Q9UH85; Q9UH86; Q9UK16;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Potassium voltage-gated channel subfamily D member 3;
DE AltName: Full=Voltage-gated potassium channel subunit Kv4.3;
GN Name=KCND3;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP FUNCTION.
RC TISSUE=Heart;
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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain, and Heart;
RX PubMed=10200233; DOI=10.1152/jn.1999.81.4.1974;
RA Dilks D., Ling H.-P., Cockett M., Sokol P., Numann R.;
RT "Cloning and expression of the human Kv4.3 potassium channel.";
RL J. Neurophysiol. 81:1974-1977(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Calmels T.P.G., Faivre J.-F., Javre J.-L., Cheval B., Rouanet S., Bril A.;
RT "Long and short human isoforms of the Kv4.3 channel: cloning, expression,
RT electrophysiology, pharmacology and phosphorylation by protein kinase C.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND TISSUE
RP 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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Heart, and Lung;
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 [8]
RP INTERACTION WITH KCNIP2; KCNE1; KCNE2; SCN1B AND KCNAB1.
RX PubMed=12297301; DOI=10.1016/s0014-5793(02)03296-9;
RA Deschenes I., Tomaselli G.F.;
RT "Modulation of Kv4.3 current by accessory subunits.";
RL FEBS Lett. 528:183-188(2002).
RN [9]
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 [10]
RP INVOLVEMENT IN BRGDA9, VARIANTS BRGDA9 PHE-450 AND ARG-600, AND
RP CHARACTERIZATION OF VARIANT BRGDA9 PHE-450.
RX PubMed=21349352; DOI=10.1016/j.hrthm.2011.02.021;
RA Giudicessi J.R., Ye D., Tester D.J., Crotti L., Mugione A.,
RA Nesterenko V.V., Albertson R.M., Antzelevitch C., Schwartz P.J.,
RA Ackerman M.J.;
RT "Transient outward current (I(to)) gain-of-function mutations in the KCND3-
RT encoded Kv4.3 potassium channel and Brugada syndrome.";
RL Heart Rhythm 8:1024-1032(2011).
RN [11]
RP INVOLVEMENT IN BRGDA9, VARIANTS BRGDA9 ILE-392; ARG-530 AND ARG-600, AND
RP CHARACTERIZATION OF VARIANTS BRGDA9 ILE-392; ARG-530 AND ARG-600.
RX PubMed=22457051; DOI=10.1002/humu.22058;
RA Giudicessi J.R., Ye D., Kritzberger C.J., Nesterenko V.V., Tester D.J.,
RA Antzelevitch C., Ackerman M.J.;
RT "Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with
RT autopsy-negative sudden unexplained death.";
RL Hum. Mutat. 33:989-997(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 29-143, AND INTERACTION WITH
RP 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 [13]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 6-145 IN COMPLEX WITH KCNIP1, AND
RP SUBUNIT.
RX PubMed=17187064; DOI=10.1038/nn1822;
RA Wang H., Yan Y., Liu Q., Huang Y., Shen Y., Chen L., Chen Y., Yang Q.,
RA Hao Q., Wang K., Chai J.;
RT "Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP
RT subunits.";
RL Nat. Neurosci. 10:32-39(2007).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] MET-94.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [15]
RP VARIANTS SCA19 PHE-227 DEL; GLU-338; VAL-345 AND MET-377, AND
RP CHARACTERIZATION OF VARIANT PHE-227 DEL.
RX PubMed=23280837; DOI=10.1002/ana.23701;
RA Lee Y.C., Durr A., Majczenko K., Huang Y.H., Liu Y.C., Lien C.C.,
RA Tsai P.C., Ichikawa Y., Goto J., Monin M.L., Li J.Z., Chung M.Y.,
RA Mundwiller E., Shakkottai V., Liu T.T., Tesson C., Lu Y.C., Brice A.,
RA Tsuji S., Burmeister M., Stevanin G., Soong B.W.;
RT "Mutations in KCND3 cause spinocerebellar ataxia type 22.";
RL Ann. Neurol. 72:859-869(2012).
RN [16]
RP VARIANTS SCA19 PRO-352; ILE-373 AND ASN-390, AND CHARACTERIZATION OF
RP VARIANTS SCA19 PRO-352; ILE-373 AND ASN-390.
RX PubMed=23280838; DOI=10.1002/ana.23700;
RA Duarri A., Jezierska J., Fokkens M., Meijer M., Schelhaas H.J.,
RA den Dunnen W.F., van Dijk F., Verschuuren-Bemelmans C., Hageman G.,
RA van de Vlies P., Kusters B., van de Warrenburg B.P., Kremer B.,
RA Wijmenga C., Sinke R.J., Swertz M.A., Kampinga H.H., Boddeke E.,
RA Verbeek D.S.;
RT "Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type
RT 19.";
RL Ann. Neurol. 72:870-880(2012).
RN [17]
RP VARIANT SCA19 SER-384.
RX PubMed=28895081; DOI=10.1007/s12311-017-0883-4;
RA Kurihara M., Ishiura H., Sasaki T., Otsuka J., Hayashi T., Terao Y.,
RA Matsukawa T., Mitsui J., Kaneko J., Nishiyama K., Doi K., Yoshimura J.,
RA Morishita S., Shimizu J., Tsuji S.;
RT "Novel de novo KCND3 mutation in a Japanese patient with intellectual
RT disability, cerebellar ataxia, myoclonus, and dystonia.";
RL Cerebellum 17:237-242(2018).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated rapidly
CC inactivating A-type potassium channels. May contribute to I(To) current
CC in heart and I(Sa) current in neurons. Channel properties are modulated
CC by interactions with other alpha subunits and with regulatory subunits.
CC {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:9843794}.
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCND1 and/or KCND2.
CC Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and
CC KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1
CC and DLG1. {ECO:0000250, ECO:0000269|PubMed:12297301,
CC ECO:0000269|PubMed:14980207, ECO:0000269|PubMed:17187064,
CC ECO:0000269|PubMed:19213956}.
CC -!- INTERACTION:
CC Q9UK17; Q9NZI2: KCNIP1; NbExp=3; IntAct=EBI-9825212, EBI-2120635;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q62897};
CC Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q62897}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q62897}. Note=Interaction with palmitoylated
CC KCNIP2 and KCNIP3 enhances cell surface expression.
CC {ECO:0000250|UniProtKB:Q62897}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=KCND3L, Long;
CC IsoId=Q9UK17-1; Sequence=Displayed;
CC Name=2; Synonyms=KCND3S, Short;
CC IsoId=Q9UK17-2; Sequence=VSP_008826;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and brain, in particular
CC in cortex, cerebellum, amygdala and caudate nucleus. Detected at lower
CC levels in liver, skeletal muscle, kidney and pancreas. Isoform 1
CC predominates in most tissues. Isoform 1 and isoform 2 are detected at
CC similar levels in brain, skeletal muscle and pancreas.
CC {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:10729221,
CC ECO:0000269|PubMed:9843794}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position.
CC -!- PTM: Regulated through phosphorylation at Ser-569 by CaMK2D.
CC {ECO:0000250}.
CC -!- DISEASE: Spinocerebellar ataxia 19 (SCA19) [MIM:607346]: A form of
CC spinocerebellar ataxia, a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA19 is a relatively mild, cerebellar
CC ataxic syndrome with cognitive impairment, pyramidal tract involvement,
CC tremor and peripheral neuropathy, and mild atrophy of the cerebellar
CC hemispheres and vermis. {ECO:0000269|PubMed:23280837,
CC ECO:0000269|PubMed:23280838, ECO:0000269|PubMed:28895081}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Brugada syndrome 9 (BRGDA9) [MIM:616399]: A tachyarrhythmia
CC characterized by right bundle branch block and ST segment elevation on
CC an electrocardiogram (ECG). It can cause the ventricles to beat so fast
CC that the blood is prevented from circulating efficiently in the body.
CC When this situation occurs, the individual will faint and may die in a
CC few minutes if the heart is not reset. {ECO:0000269|PubMed:21349352,
CC ECO:0000269|PubMed:22457051}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the potassium channel family. D (Shal) (TC
CC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Potassium voltage-gated channel, Shal-related
CC subfamily, member 3 (KCND3); Note=Leiden Open Variation Database
CC (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/KCND3";
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DR EMBL; AF048712; AAC05121.1; -; mRNA.
DR EMBL; AF048713; AAC05122.1; -; mRNA.
DR EMBL; AF187963; AAF01044.1; -; mRNA.
DR EMBL; AF187964; AAF01045.1; -; mRNA.
DR EMBL; AF205856; AAF20924.1; -; mRNA.
DR EMBL; AF205857; AAF20925.1; -; mRNA.
DR EMBL; AF120491; AAD38898.1; -; mRNA.
DR EMBL; AF166011; AAF68177.1; -; Genomic_DNA.
DR EMBL; AF166009; AAF68177.1; JOINED; Genomic_DNA.
DR EMBL; AF166010; AAF68177.1; JOINED; Genomic_DNA.
DR EMBL; AF166011; AAF68178.1; -; Genomic_DNA.
DR EMBL; AF166009; AAF68178.1; JOINED; Genomic_DNA.
DR EMBL; AF166010; AAF68178.1; JOINED; Genomic_DNA.
DR EMBL; AL512665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450997; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049557; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56511.1; -; Genomic_DNA.
DR EMBL; BC113475; AAI13476.1; -; mRNA.
DR EMBL; BC113477; AAI13478.1; -; mRNA.
DR CCDS; CCDS843.1; -. [Q9UK17-1]
DR CCDS; CCDS844.1; -. [Q9UK17-2]
DR RefSeq; NP_004971.2; NM_004980.4. [Q9UK17-1]
DR RefSeq; NP_751948.1; NM_172198.2. [Q9UK17-2]
DR RefSeq; XP_005270908.1; XM_005270851.4.
DR RefSeq; XP_006710692.1; XM_006710629.3. [Q9UK17-1]
DR RefSeq; XP_006710693.1; XM_006710630.3.
DR RefSeq; XP_016856733.1; XM_017001244.1. [Q9UK17-1]
DR PDB; 1S1G; X-ray; 2.60 A; A/B=29-143.
DR PDB; 2NZ0; X-ray; 3.20 A; B/D=6-145.
DR PDBsum; 1S1G; -.
DR PDBsum; 2NZ0; -.
DR AlphaFoldDB; Q9UK17; -.
DR SMR; Q9UK17; -.
DR BioGRID; 109954; 43.
DR ComplexPortal; CPX-3256; Kv4.3-KChIP1 channel complex.
DR CORUM; Q9UK17; -.
DR IntAct; Q9UK17; 2.
DR STRING; 9606.ENSP00000319591; -.
DR BindingDB; Q9UK17; -.
DR ChEMBL; CHEMBL1964; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB06217; Vernakalant.
DR DrugCentral; Q9UK17; -.
DR TCDB; 1.A.1.2.19; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q9UK17; -.
DR PhosphoSitePlus; Q9UK17; -.
DR BioMuta; KCND3; -.
DR DMDM; 92090984; -.
DR MassIVE; Q9UK17; -.
DR PaxDb; Q9UK17; -.
DR PeptideAtlas; Q9UK17; -.
DR PRIDE; Q9UK17; -.
DR ProteomicsDB; 84705; -. [Q9UK17-1]
DR ProteomicsDB; 84706; -. [Q9UK17-2]
DR ABCD; Q9UK17; 2 sequenced antibodies.
DR Antibodypedia; 20128; 217 antibodies from 30 providers.
DR DNASU; 3752; -.
DR Ensembl; ENST00000302127.5; ENSP00000306923.4; ENSG00000171385.10. [Q9UK17-1]
DR Ensembl; ENST00000315987.6; ENSP00000319591.2; ENSG00000171385.10. [Q9UK17-1]
DR Ensembl; ENST00000369697.5; ENSP00000358711.1; ENSG00000171385.10. [Q9UK17-2]
DR GeneID; 3752; -.
DR KEGG; hsa:3752; -.
DR MANE-Select; ENST00000302127.5; ENSP00000306923.4; NM_001378969.1; NP_001365898.1.
DR UCSC; uc001ebu.2; human. [Q9UK17-1]
DR CTD; 3752; -.
DR DisGeNET; 3752; -.
DR GeneCards; KCND3; -.
DR GeneReviews; KCND3; -.
DR HGNC; HGNC:6239; KCND3.
DR HPA; ENSG00000171385; Tissue enhanced (brain).
DR MalaCards; KCND3; -.
DR MIM; 605411; gene.
DR MIM; 607346; phenotype.
DR MIM; 616399; phenotype.
DR neXtProt; NX_Q9UK17; -.
DR OpenTargets; ENSG00000171385; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 98772; Spinocerebellar ataxia type 19/22.
DR PharmGKB; PA210; -.
DR VEuPathDB; HostDB:ENSG00000171385; -.
DR eggNOG; KOG4390; Eukaryota.
DR GeneTree; ENSGT00940000155343; -.
DR HOGENOM; CLU_011722_9_1_1; -.
DR InParanoid; Q9UK17; -.
DR OMA; XKARLAR; -.
DR OrthoDB; 469107at2759; -.
DR PhylomeDB; Q9UK17; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q9UK17; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR Reactome; R-HSA-5576894; Phase 1 - inactivation of fast Na+ channels.
DR SignaLink; Q9UK17; -.
DR SIGNOR; Q9UK17; -.
DR BioGRID-ORCS; 3752; 20 hits in 1073 CRISPR screens.
DR ChiTaRS; KCND3; human.
DR EvolutionaryTrace; Q9UK17; -.
DR GeneWiki; KCND3; -.
DR GenomeRNAi; 3752; -.
DR Pharos; Q9UK17; Tclin.
DR PRO; PR:Q9UK17; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UK17; protein.
DR Bgee; ENSG00000171385; Expressed in cerebellar vermis and 184 other tissues.
DR ExpressionAtlas; Q9UK17; baseline and differential.
DR Genevisible; Q9UK17; HS.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
DR GO; GO:0005250; F:A-type (transient outward) potassium channel activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0086009; P:membrane repolarization; IDA:BHF-UCL.
DR GO; GO:0086013; P:membrane repolarization during cardiac muscle cell action potential; TAS:BHF-UCL.
DR GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; IEA:GOC.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0099625; P:ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
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; IPR004056; K_chnl_volt-dep_Kv4.3.
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; PR01518; KV43CHANNEL.
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; Alternative splicing; Brugada syndrome; Cell membrane;
KW Cell projection; Disease variant; Ion channel; Ion transport; Membrane;
KW Metal-binding; Neurodegeneration; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome;
KW Spinocerebellar ataxia; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel; Zinc.
FT CHAIN 1..655
FT /note="Potassium voltage-gated channel subfamily D member
FT 3"
FT /id="PRO_0000054068"
FT TOPO_DOM 1..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..256
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..307
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT INTRAMEM 360..380
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 2..20
FT /note="Interaction with KCNIP2"
FT /evidence="ECO:0000250"
FT REGION 472..487
FT /note="Mediates dendritic targeting"
FT /evidence="ECO:0000250"
FT REGION 525..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 615..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 367..372
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 624..639
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 640..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V1"
FT MOD_RES 459
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V1"
FT MOD_RES 569
FT /note="Phosphoserine; by CaMK2D"
FT /evidence="ECO:0000250|UniProtKB:Q62897"
FT MOD_RES 585
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0V1"
FT VAR_SEQ 488..506
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10200233,
FT ECO:0000303|PubMed:10729221, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9843794"
FT /id="VSP_008826"
FT VARIANT 94
FT /note="V -> M (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1349469134)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035775"
FT VARIANT 227
FT /note="Missing (in SCA19; results in reduced channel
FT activity consistent with impaired cell surface expression
FT of the mutant protein)"
FT /evidence="ECO:0000269|PubMed:23280837"
FT /id="VAR_070785"
FT VARIANT 338
FT /note="V -> E (in SCA19)"
FT /evidence="ECO:0000269|PubMed:23280837"
FT /id="VAR_070786"
FT VARIANT 345
FT /note="G -> V (in SCA19; dbSNP:rs797045634)"
FT /evidence="ECO:0000269|PubMed:23280837"
FT /id="VAR_070787"
FT VARIANT 352
FT /note="T -> P (in SCA19; loss of channel activity;
FT dbSNP:rs397515476)"
FT /evidence="ECO:0000269|PubMed:23280838"
FT /id="VAR_070788"
FT VARIANT 373
FT /note="M -> I (in SCA19; unknown pathological significance;
FT causes reduced channel activity; dbSNP:rs397515477)"
FT /evidence="ECO:0000269|PubMed:23280838"
FT /id="VAR_070789"
FT VARIANT 377
FT /note="T -> M (in SCA19)"
FT /evidence="ECO:0000269|PubMed:23280837"
FT /id="VAR_070790"
FT VARIANT 384
FT /note="G -> S (in SCA19)"
FT /evidence="ECO:0000269|PubMed:28895081"
FT /id="VAR_079709"
FT VARIANT 390
FT /note="S -> N (in SCA19; unknown pathological significance;
FT results in impaired cell surface expression;
FT dbSNP:rs397515478)"
FT /evidence="ECO:0000269|PubMed:23280838"
FT /id="VAR_070791"
FT VARIANT 392
FT /note="V -> I (in BRGDA9; unknown pathological
FT significance; gain of function mutation;
FT dbSNP:rs786205867)"
FT /evidence="ECO:0000269|PubMed:22457051"
FT /id="VAR_067694"
FT VARIANT 450
FT /note="L -> F (in BRGDA9; unknown pathological
FT significance; gain of function mutation;
FT dbSNP:rs150401343)"
FT /evidence="ECO:0000269|PubMed:21349352"
FT /id="VAR_073831"
FT VARIANT 530
FT /note="S -> R (in BRGDA9; unknown pathological
FT significance; does not affect the electrophysiological
FT properties of the channel)"
FT /evidence="ECO:0000269|PubMed:22457051"
FT /id="VAR_067695"
FT VARIANT 600
FT /note="G -> R (in BRGDA9; unknown pathological
FT significance; gain of function mutation;
FT dbSNP:rs149344567)"
FT /evidence="ECO:0000269|PubMed:21349352,
FT ECO:0000269|PubMed:22457051"
FT /id="VAR_067696"
FT CONFLICT 239
FT /note="V -> G (in Ref. 1; AAC05121/AAC05122 and 4;
FT AAD38898)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="P -> L (in Ref. 1; AAC05121/AAC05122 and 4;
FT AAD38898)"
FT /evidence="ECO:0000305"
FT CONFLICT 408
FT /note="R -> G (in Ref. 2; AAF01044/AAF01045)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="E -> G (in Ref. 2; AAF01044/AAF01045)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="T -> Q (in Ref. 2; AAF01044/AAF01045)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="A -> D (in Ref. 2; AAF01044/AAF01045)"
FT /evidence="ECO:0000305"
FT CONFLICT 646
FT /note="A -> T (in Ref. 1; AAC05121/AAC05122, 2; AAF01045
FT and 4; AAD38898)"
FT /evidence="ECO:0000305"
FT CONFLICT 654
FT /note="A -> V (in Ref. 1; AAC05121/AAC05122, 2; AAF01044
FT and 4; AAD38898)"
FT /evidence="ECO:0000305"
FT HELIX 9..14
FT /evidence="ECO:0007829|PDB:2NZ0"
FT TURN 15..19
FT /evidence="ECO:0007829|PDB:2NZ0"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:2NZ0"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:2NZ0"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:1S1G"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:1S1G"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:1S1G"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:2NZ0"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:1S1G"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2NZ0"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1S1G"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:1S1G"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:1S1G"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2NZ0"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:1S1G"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1S1G"
FT HELIX 130..144
FT /evidence="ECO:0007829|PDB:1S1G"
SQ SEQUENCE 655 AA; 73451 MW; ADD1402A97204764 CRC64;
MAAGVAAWLP FARAAAIGWM PVANCPMPLA PADKNKRQDE LIVLNVSGRR FQTWRTTLER
YPDTLLGSTE KEFFFNEDTK EYFFDRDPEV FRCVLNFYRT GKLHYPRYEC ISAYDDELAF
YGILPEIIGD CCYEEYKDRK RENAERLMDD NDSENNQESM PSLSFRQTMW RAFENPHTST
LALVFYYVTG FFIAVSVITN VVETVPCGTV PGSKELPCGE RYSVAFFCLD TACVMIFTVE
YLLRLFAAPS RYRFIRSVMS IIDVVAIMPY YIGLVMTNNE DVSGAFVTLR VFRVFRIFKF
SRHSQGLRIL GYTLKSCASE LGFLLFSLTM AIIIFATVMF YAEKGSSASK FTSIPASFWY
TIVTMTTLGY GDMVPKTIAG KIFGSICSLS GVLVIALPVP VIVSNFSRIY HQNQRADKRR
AQKKARLARI RVAKTGSSNA YLHSKRNGLL NEALELTGTP EEEHMGKTTS LIESQHHHLL
HCLEKTTGLS YLVDDPLLSV RTSTIKNHEF IDEQMFEQNC MESSMQNYPS TRSPSLSSHP
GLTTTCCSRR SKKTTHLPNS NLPATRLRSM QELSTIHIQG SEQPSLTTSR SSLNLKADDG
LRPNCKTSQI TTAIISIPTP PALTPEGESR PPPASPGPNT NIPSIASNVV KVSAL
