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Protein

Potassium voltage-gated channel subfamily D member 3

Gene

KCND3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi104Zinc1
Metal bindingi131Zinc1
Metal bindingi132Zinc1

GO - Molecular functioni

  • A-type (transient outward) potassium channel activity Source: ProtInc
  • ion channel binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cardiac conduction Source: Reactome
  • membrane repolarization Source: BHF-UCL
  • membrane repolarization during cardiac muscle cell action potential Source: BHF-UCL
  • membrane repolarization during ventricular cardiac muscle cell action potential Source: GOC
  • potassium ion export Source: BHF-UCL
  • potassium ion export across plasma membrane Source: BHF-UCL
  • potassium ion transport Source: ProtInc
  • protein homooligomerization Source: InterPro
  • regulation of heart rate by cardiac conduction Source: BHF-UCL
  • regulation of ion transmembrane transport Source: UniProtKB-KW
  • ventricular cardiac muscle cell membrane repolarization Source: BHF-UCL

Keywordsi

Molecular functionIon channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandMetal-binding, Potassium, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels
R-HSA-5576894 Phase 1 - inactivation of fast Na+ channels

Protein family/group databases

TCDBi1.A.1.2.19 the voltage-gated ion channel (vic) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily D member 3
Alternative name(s):
Voltage-gated potassium channel subunit Kv4.3
Gene namesi
Name:KCND3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000171385.9
HGNCiHGNC:6239 KCND3
MIMi605411 gene
neXtProtiNX_Q9UK17

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 181CytoplasmicSequence analysisAdd BLAST181
Transmembranei182 – 202Helical; Name=Segment S1Sequence analysisAdd BLAST21
Transmembranei222 – 242Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini243 – 256CytoplasmicSequence analysisAdd BLAST14
Transmembranei257 – 277Helical; Name=Segment S3Sequence analysisAdd BLAST21
Transmembranei287 – 307Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini308 – 320CytoplasmicSequence analysisAdd BLAST13
Transmembranei321 – 341Helical; Name=Segment S5Sequence analysisAdd BLAST21
Intramembranei360 – 380Pore-forming; Name=Segment H5Sequence analysisAdd BLAST21
Transmembranei382 – 402Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini403 – 655CytoplasmicSequence analysisAdd BLAST253

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 19 (SCA19)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis.
See also OMIM:607346
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070785227Missing in SCA19; results in reduced channel activity consistent with impaired cell surface expression of the mutant protein. 1 Publication1
Natural variantiVAR_070786338V → E in SCA19. 1 Publication1
Natural variantiVAR_070787345G → V in SCA19. 1 PublicationCorresponds to variant dbSNP:rs797045634Ensembl.1
Natural variantiVAR_070788352T → P in SCA19; loss of channel activity. 1 PublicationCorresponds to variant dbSNP:rs397515476Ensembl.1
Natural variantiVAR_070789373M → I in SCA19; causes reduced channel activity. 1 PublicationCorresponds to variant dbSNP:rs397515477Ensembl.1
Natural variantiVAR_070790377T → M in SCA19. 1 Publication1
Natural variantiVAR_079709384G → S in SCA19. 1 Publication1
Natural variantiVAR_070791390S → N in SCA19; results in impaired cell surface expression. 1 PublicationCorresponds to variant dbSNP:rs397515478Ensembl.1
Brugada syndrome 9 (BRGDA9)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
See also OMIM:616399
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067694392V → I in BRGDA9; gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs786205867Ensembl.1
Natural variantiVAR_073831450L → F in BRGDA9; gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs150401343Ensembl.1
Natural variantiVAR_067695530S → R in BRGDA9; does not affect the electrophysiological properties of the channel. 1 Publication1
Natural variantiVAR_067696600G → R in BRGDA9; gain of function mutation. 2 PublicationsCorresponds to variant dbSNP:rs149344567Ensembl.1

Keywords - Diseasei

Brugada syndrome, Disease mutation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi3752
MalaCardsiKCND3
MIMi607346 phenotype
616399 phenotype
OpenTargetsiENSG00000171385
Orphaneti130 Brugada syndrome
98772 Spinocerebellar ataxia type 19/22
PharmGKBiPA210

Chemistry databases

ChEMBLiCHEMBL1964
DrugBankiDB00321 Amitriptyline
DB06637 Dalfampridine
DB00280 Disopyramide
DB00458 Imipramine

Polymorphism and mutation databases

BioMutaiKCND3
DMDMi92090984

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540681 – 655Potassium voltage-gated channel subfamily D member 3Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei153PhosphoserineBy similarity1
Modified residuei459PhosphothreonineBy similarity1
Modified residuei569Phosphoserine; by CaMK2DBy similarity1
Modified residuei585PhosphoserineBy similarity1

Post-translational modificationi

Regulated through phosphorylation at Ser-569 by CaMK2D.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UK17
PaxDbiQ9UK17
PeptideAtlasiQ9UK17
PRIDEiQ9UK17

PTM databases

iPTMnetiQ9UK17
PhosphoSitePlusiQ9UK17

Expressioni

Tissue specificityi

Highly expressed in heart and brain, in particular in cortex, cerebellum, amygdala and caudate nucleus. Detected at lower levels in liver, skeletal muscle, kidney and pancreas. Isoform 1 predominates in most tissues. Isoform 1 and isoform 2 are detected at similar levels in brain, skeletal muscle and pancreas.3 Publications

Gene expression databases

BgeeiENSG00000171385
CleanExiHS_KCND3
ExpressionAtlasiQ9UK17 baseline and differential
GenevisibleiQ9UK17 HS

Organism-specific databases

HPAiHPA029452

Interactioni

Subunit structurei

Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KCNIP1Q9NZI23EBI-9825212,EBI-2120635

GO - Molecular functioni

  • ion channel binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi10995435 interactors.
CORUMiQ9UK17
IntActiQ9UK17 1 interactor.
STRINGi9606.ENSP00000319591

Chemistry databases

BindingDBiQ9UK17

Structurei

Secondary structure

1655
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 14Combined sources6
Turni15 – 19Combined sources5
Beta strandi20 – 23Combined sources4
Helixi32 – 34Combined sources3
Beta strandi41 – 46Combined sources6
Beta strandi49 – 54Combined sources6
Helixi55 – 58Combined sources4
Turni65 – 67Combined sources3
Helixi70 – 73Combined sources4
Beta strandi74 – 76Combined sources3
Beta strandi77 – 79Combined sources3
Beta strandi81 – 84Combined sources4
Helixi88 – 100Combined sources13
Beta strandi101 – 103Combined sources3
Helixi111 – 120Combined sources10
Helixi125 – 127Combined sources3
Helixi130 – 144Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S1GX-ray2.60A/B29-143[»]
2NZ0X-ray3.20B/D6-145[»]
ProteinModelPortaliQ9UK17
SMRiQ9UK17
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UK17

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 20Interaction with KCNIP2By similarityAdd BLAST19
Regioni472 – 487Mediates dendritic targetingBy similarityAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi367 – 372Selectivity filterBy similarity6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4390 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00760000118846
HOVERGENiHBG106687
InParanoidiQ9UK17
KOiK04893
OMAiGTCCTRR
OrthoDBiEOG091G18X0
PhylomeDBiQ9UK17
TreeFamiTF313103

Family and domain databases

Gene3Di1.20.120.3501 hit
InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR005821 Ion_trans_dom
IPR003968 K_chnl_volt-dep_Kv
IPR003975 K_chnl_volt-dep_Kv4
IPR004056 K_chnl_volt-dep_Kv4.3
IPR024587 K_chnl_volt-dep_Kv4_C
IPR021645 Shal-type_N
IPR011333 SKP1/BTB/POZ_sf
IPR003131 T1-type_BTB
IPR028325 VG_K_chnl
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR11537 PTHR11537, 4 hits
PfamiView protein in Pfam
PF02214 BTB_2, 1 hit
PF11879 DUF3399, 1 hit
PF00520 Ion_trans, 1 hit
PF11601 Shal-type, 1 hit
PRINTSiPR00169 KCHANNEL
PR01518 KV43CHANNEL
PR01491 KVCHANNEL
PR01497 SHALCHANNEL
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SUPFAMiSSF54695 SSF54695, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UK17-1) [UniParc]FASTAAdd to basket
Also known as: KCND3L, Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAGVAAWLP FARAAAIGWM PVANCPMPLA PADKNKRQDE LIVLNVSGRR
60 70 80 90 100
FQTWRTTLER YPDTLLGSTE KEFFFNEDTK EYFFDRDPEV FRCVLNFYRT
110 120 130 140 150
GKLHYPRYEC ISAYDDELAF YGILPEIIGD CCYEEYKDRK RENAERLMDD
160 170 180 190 200
NDSENNQESM PSLSFRQTMW RAFENPHTST LALVFYYVTG FFIAVSVITN
210 220 230 240 250
VVETVPCGTV PGSKELPCGE RYSVAFFCLD TACVMIFTVE YLLRLFAAPS
260 270 280 290 300
RYRFIRSVMS IIDVVAIMPY YIGLVMTNNE DVSGAFVTLR VFRVFRIFKF
310 320 330 340 350
SRHSQGLRIL GYTLKSCASE LGFLLFSLTM AIIIFATVMF YAEKGSSASK
360 370 380 390 400
FTSIPASFWY TIVTMTTLGY GDMVPKTIAG KIFGSICSLS GVLVIALPVP
410 420 430 440 450
VIVSNFSRIY HQNQRADKRR AQKKARLARI RVAKTGSSNA YLHSKRNGLL
460 470 480 490 500
NEALELTGTP EEEHMGKTTS LIESQHHHLL HCLEKTTGLS YLVDDPLLSV
510 520 530 540 550
RTSTIKNHEF IDEQMFEQNC MESSMQNYPS TRSPSLSSHP GLTTTCCSRR
560 570 580 590 600
SKKTTHLPNS NLPATRLRSM QELSTIHIQG SEQPSLTTSR SSLNLKADDG
610 620 630 640 650
LRPNCKTSQI TTAIISIPTP PALTPEGESR PPPASPGPNT NIPSIASNVV

KVSAL
Length:655
Mass (Da):73,451
Last modified:March 7, 2006 - v3
Checksum:iADD1402A97204764
GO
Isoform 2 (identifier: Q9UK17-2) [UniParc]FASTAAdd to basket
Also known as: KCND3S, Short

The sequence of this isoform differs from the canonical sequence as follows:
     488-506: Missing.

Show »
Length:636
Mass (Da):71,392
Checksum:i9414269BB8A53D29
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti239V → G in AAC05121 (PubMed:9843794).Curated1
Sequence conflicti239V → G in AAC05122 (PubMed:9843794).Curated1
Sequence conflicti239V → G in AAD38898 (PubMed:10729221).Curated1
Sequence conflicti375P → L in AAC05121 (PubMed:9843794).Curated1
Sequence conflicti375P → L in AAC05122 (PubMed:9843794).Curated1
Sequence conflicti375P → L in AAD38898 (PubMed:10729221).Curated1
Sequence conflicti408R → G in AAF01044 (PubMed:10200233).Curated1
Sequence conflicti408R → G in AAF01045 (PubMed:10200233).Curated1
Sequence conflicti452E → G in AAF01044 (PubMed:10200233).Curated1
Sequence conflicti452E → G in AAF01045 (PubMed:10200233).Curated1
Sequence conflicti531T → Q in AAF01044 (PubMed:10200233).Curated1
Sequence conflicti531T → Q in AAF01045 (PubMed:10200233).Curated1
Sequence conflicti564A → D in AAF01044 (PubMed:10200233).Curated1
Sequence conflicti564A → D in AAF01045 (PubMed:10200233).Curated1
Sequence conflicti646A → T in AAC05121 (PubMed:9843794).Curated1
Sequence conflicti646A → T in AAC05122 (PubMed:9843794).Curated1
Sequence conflicti646A → T in AAF01045 (PubMed:10200233).Curated1
Sequence conflicti646A → T in AAD38898 (PubMed:10729221).Curated1
Sequence conflicti654A → V in AAC05121 (PubMed:9843794).Curated1
Sequence conflicti654A → V in AAC05122 (PubMed:9843794).Curated1
Sequence conflicti654A → V in AAF01044 (PubMed:10200233).Curated1
Sequence conflicti654A → V in AAD38898 (PubMed:10729221).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03577594V → M in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_070785227Missing in SCA19; results in reduced channel activity consistent with impaired cell surface expression of the mutant protein. 1 Publication1
Natural variantiVAR_070786338V → E in SCA19. 1 Publication1
Natural variantiVAR_070787345G → V in SCA19. 1 PublicationCorresponds to variant dbSNP:rs797045634Ensembl.1
Natural variantiVAR_070788352T → P in SCA19; loss of channel activity. 1 PublicationCorresponds to variant dbSNP:rs397515476Ensembl.1
Natural variantiVAR_070789373M → I in SCA19; causes reduced channel activity. 1 PublicationCorresponds to variant dbSNP:rs397515477Ensembl.1
Natural variantiVAR_070790377T → M in SCA19. 1 Publication1
Natural variantiVAR_079709384G → S in SCA19. 1 Publication1
Natural variantiVAR_070791390S → N in SCA19; results in impaired cell surface expression. 1 PublicationCorresponds to variant dbSNP:rs397515478Ensembl.1
Natural variantiVAR_067694392V → I in BRGDA9; gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs786205867Ensembl.1
Natural variantiVAR_073831450L → F in BRGDA9; gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs150401343Ensembl.1
Natural variantiVAR_067695530S → R in BRGDA9; does not affect the electrophysiological properties of the channel. 1 Publication1
Natural variantiVAR_067696600G → R in BRGDA9; gain of function mutation. 2 PublicationsCorresponds to variant dbSNP:rs149344567Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008826488 – 506Missing in isoform 2. 4 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF048712 mRNA Translation: AAC05121.1
AF048713 mRNA Translation: AAC05122.1
AF187963 mRNA Translation: AAF01044.1
AF187964 mRNA Translation: AAF01045.1
AF205856 mRNA Translation: AAF20924.1
AF205857 mRNA Translation: AAF20925.1
AF120491 mRNA Translation: AAD38898.1
AF166011, AF166009, AF166010 Genomic DNA Translation: AAF68177.1
AF166011, AF166009, AF166010 Genomic DNA Translation: AAF68178.1
AL512665 Genomic DNA No translation available.
AL450997 Genomic DNA No translation available.
AL049557 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56511.1
BC113475 mRNA Translation: AAI13476.1
BC113477 mRNA Translation: AAI13478.1
CCDSiCCDS843.1 [Q9UK17-1]
CCDS844.1 [Q9UK17-2]
RefSeqiNP_004971.2, NM_004980.4 [Q9UK17-1]
NP_751948.1, NM_172198.2 [Q9UK17-2]
XP_005270908.1, XM_005270851.4 [Q9UK17-1]
XP_006710692.1, XM_006710629.3 [Q9UK17-1]
XP_006710693.1, XM_006710630.3 [Q9UK17-2]
XP_016856733.1, XM_017001244.1 [Q9UK17-1]
UniGeneiHs.666367
Hs.730579

Genome annotation databases

EnsembliENST00000302127; ENSP00000306923; ENSG00000171385 [Q9UK17-2]
ENST00000315987; ENSP00000319591; ENSG00000171385 [Q9UK17-1]
ENST00000369697; ENSP00000358711; ENSG00000171385 [Q9UK17-2]
GeneIDi3752
KEGGihsa:3752
UCSCiuc001ebu.2 human [Q9UK17-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKCND3_HUMAN
AccessioniPrimary (citable) accession number: Q9UK17
Secondary accession number(s): O60576
, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: March 7, 2006
Last modified: February 28, 2018
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome