Q9UK17 (KCND3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily D member 3

Alternative name(s):
Voltage-gated potassium channel subunit Kv4.3

Gene names

Name:

KCND3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	655 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2
Subunit structure	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. Ref.6 Ref.8 Ref.9 Ref.10
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane › sarcolemma By similarity.
Tissue specificity	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. Ref.1 Ref.2 Ref.4
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Post-translational modification	Regulated through phosphorylation at Ser-569 by CaMK2D By similarity.
Sequence similarities	Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Metal-binding Potassium Zinc
Molecular function	Ionic channel Potassium channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	synaptic transmission Traceable author statement. Source: Reactome
Cellular component	sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell voltage-gated potassium channel complex Traceable author statement. Source: ProtInc
Molecular function	A-type (transient outward) potassium channel activity Traceable author statement. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UK17-1)

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.

Isoform 2 (identifier: Q9UK17-2)

Also known as: KCND3S; Short;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 655

655

Potassium voltage-gated channel subfamily D member 3

PRO_0000054068

Regions

Topological domain

1 – 181

181

Cytoplasmic Potential

Transmembrane

182 – 202

21

Helical; Name=Segment S1; Potential

Transmembrane

222 – 242

21

Helical; Name=Segment S2; Potential

Topological domain

243 – 256

14

Cytoplasmic Potential

Transmembrane

257 – 277

21

Helical; Name=Segment S3; Potential

Transmembrane

287 – 307

21

Helical; Voltage-sensor; Name=Segment S4; Potential

Topological domain

308 – 320

13

Cytoplasmic Potential

Transmembrane

321 – 341

21

Helical; Name=Segment S5; Potential

Intramembrane

360 – 380

21

Pore-forming; Name=Segment H5; Potential

Transmembrane

382 – 402

21

Helical; Name=Segment S6; Potential

Topological domain

403 – 655

253

Cytoplasmic Potential

Region

2 – 20

19

Interaction with KCNIP2 By similarity

Motif

367 – 372

6

Selectivity filter By similarity

Sites

Metal binding

104

1

Zinc

Metal binding

131

1

Zinc

Metal binding

132

1

Zinc

Amino acid modifications

Modified residue

435

1

Phosphothreonine Ref.7

Modified residue

441

1

Phosphotyrosine Ref.7

Modified residue

569

1

Phosphoserine; by CaMK2D By similarity

Natural variations

Alternative sequence

488 – 506

19

Missing in isoform 2.

VSP_008826

Natural variant

94

1

V → M in a colorectal cancer sample; somatic mutation. Ref.11

VAR_035775

Experimental info

Sequence conflict

239

1

V → G in AAC05121. Ref.1

Sequence conflict

239

1

V → G in AAC05122. Ref.1

Sequence conflict

239

1

V → G in AAD38898. Ref.4

Sequence conflict

375

1

P → L in AAC05121. Ref.1

Sequence conflict

375

1

P → L in AAC05122. Ref.1

Sequence conflict

375

1

P → L in AAD38898. Ref.4

Sequence conflict

408

1

R → G in AAF01044. Ref.2

Sequence conflict

408

1

R → G in AAF01045. Ref.2

Sequence conflict

452

1

E → G in AAF01044. Ref.2

Sequence conflict

452

1

E → G in AAF01045. Ref.2

Sequence conflict

531

1

T → Q in AAF01044. Ref.2

Sequence conflict

531

1

T → Q in AAF01045. Ref.2

Sequence conflict

564

1

A → D in AAF01044. Ref.2

Sequence conflict

564

1

A → D in AAF01045. Ref.2

Sequence conflict

646

1

A → T in AAC05121. Ref.1

Sequence conflict

646

1

A → T in AAC05122. Ref.1

Sequence conflict

646

1

A → T in AAF01045. Ref.2

Sequence conflict

646

1

A → T in AAD38898. Ref.4

Sequence conflict

654

1

A → V in AAC05121. Ref.1

Sequence conflict

654

1

A → V in AAC05122. Ref.1

Sequence conflict

654

1

A → V in AAF01044. Ref.2

Sequence conflict

654

1

A → V in AAD38898. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

655

Helix Strand Turn

Details...

Helix

9 – 14

6

Turn

15 – 19

5

Beta strand

20 – 23

4

Helix

32 – 34

3

Beta strand

41 – 46

6

Beta strand

49 – 54

6

Helix

55 – 58

4

Helix

70 – 73

4

Beta strand

77 – 79

3

Beta strand

81 – 84

4

Helix

88 – 100

13

Helix

111 – 120

10

Helix

125 – 127

3

Helix

130 – 144

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KCND3L) (Long) [UniParc]. Last modified March 7, 2006. Version 3. Checksum: ADD1402A97204764	FASTA	655	73,451
	10 20 30 40 50 60 MAAGVAAWLP FARAAAIGWM PVANCPMPLA PADKNKRQDE LIVLNVSGRR FQTWRTTLER 70 80 90 100 110 120 YPDTLLGSTE KEFFFNEDTK EYFFDRDPEV FRCVLNFYRT GKLHYPRYEC ISAYDDELAF 130 140 150 160 170 180 YGILPEIIGD CCYEEYKDRK RENAERLMDD NDSENNQESM PSLSFRQTMW RAFENPHTST 190 200 210 220 230 240 LALVFYYVTG FFIAVSVITN VVETVPCGTV PGSKELPCGE RYSVAFFCLD TACVMIFTVE 250 260 270 280 290 300 YLLRLFAAPS RYRFIRSVMS IIDVVAIMPY YIGLVMTNNE DVSGAFVTLR VFRVFRIFKF 310 320 330 340 350 360 SRHSQGLRIL GYTLKSCASE LGFLLFSLTM AIIIFATVMF YAEKGSSASK FTSIPASFWY 370 380 390 400 410 420 TIVTMTTLGY GDMVPKTIAG KIFGSICSLS GVLVIALPVP VIVSNFSRIY HQNQRADKRR 430 440 450 460 470 480 AQKKARLARI RVAKTGSSNA YLHSKRNGLL NEALELTGTP EEEHMGKTTS LIESQHHHLL 490 500 510 520 530 540 HCLEKTTGLS YLVDDPLLSV RTSTIKNHEF IDEQMFEQNC MESSMQNYPS TRSPSLSSHP 550 560 570 580 590 600 GLTTTCCSRR SKKTTHLPNS NLPATRLRSM QELSTIHIQG SEQPSLTTSR SSLNLKADDG 610 620 630 640 650 LRPNCKTSQI TTAIISIPTP PALTPEGESR PPPASPGPNT NIPSIASNVV KVSAL
	Isoform 2 (KCND3S) (Short) [UniParc]. Checksum: 9414269BB8A53D29	FASTA	636	71,392
	10 20 30 40 50 60 MAAGVAAWLP FARAAAIGWM PVANCPMPLA PADKNKRQDE LIVLNVSGRR FQTWRTTLER 70 80 90 100 110 120 YPDTLLGSTE KEFFFNEDTK EYFFDRDPEV FRCVLNFYRT GKLHYPRYEC ISAYDDELAF 130 140 150 160 170 180 YGILPEIIGD CCYEEYKDRK RENAERLMDD NDSENNQESM PSLSFRQTMW RAFENPHTST 190 200 210 220 230 240 LALVFYYVTG FFIAVSVITN VVETVPCGTV PGSKELPCGE RYSVAFFCLD TACVMIFTVE 250 260 270 280 290 300 YLLRLFAAPS RYRFIRSVMS IIDVVAIMPY YIGLVMTNNE DVSGAFVTLR VFRVFRIFKF 310 320 330 340 350 360 SRHSQGLRIL GYTLKSCASE LGFLLFSLTM AIIIFATVMF YAEKGSSASK FTSIPASFWY 370 380 390 400 410 420 TIVTMTTLGY GDMVPKTIAG KIFGSICSLS GVLVIALPVP VIVSNFSRIY HQNQRADKRR 430 440 450 460 470 480 AQKKARLARI RVAKTGSSNA YLHSKRNGLL NEALELTGTP EEEHMGKTTS LIESQHHHLL 490 500 510 520 530 540 HCLEKTTNHE FIDEQMFEQN CMESSMQNYP STRSPSLSSH PGLTTTCCSR RSKKTTHLPN 550 560 570 580 590 600 SNLPATRLRS MQELSTIHIQ GSEQPSLTTS RSSLNLKADD GLRPNCKTSQ ITTAIISIPT 610 620 630 PPALTPEGES RPPPASPGPN TNIPSIASNV VKVSAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing." Kong W., Po S., Yamagishi T., Ashen M.D., Stetten G., Tomaselli G.F. Am. J. Physiol. 275:H1963-H1970(1998) [PubMed: 9843794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, FUNCTION. Tissue: Heart.
[2]	"Cloning and expression of the human Kv4.3 potassium channel." Dilks D., Ling H.-P., Cockett M., Sokol P., Numann R. J. Neurophysiol. 81:1974-1977(1999) [PubMed: 10200233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Brain and Heart.
[3]	"Long and short human isoforms of the Kv4.3 channel: cloning, expression, electrophysiology, pharmacology and phosphorylation by protein kinase C." Calmels T.P.G., Faivre J.-F., Javre J.-L., Cheval B., Rouanet S., Bril A. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[4]	"Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA)." Isbrandt D., Leicher T., Waldschuetz R., Zhu X.-R., Luhmann U., Michel U., Sauter K., Pongs O. Genomics 64:144-154(2000) [PubMed: 10729221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Brain cortex.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Modulation of Kv4.3 current by accessory subunits." Deschenes I., Tomaselli G.F. FEBS Lett. 528:183-188(2002) [PubMed: 12297301] [Abstract] Cited for: INTERACTION WITH KCNIP2; KCNE1; KCNE2; SCN1B AND KCNAB1.
[7]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-435 AND TYR-441, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes." El-Haou S., Balse E., Neyroud N., Dilanian G., Gavillet B., Abriel H., Coulombe A., Jeromin A., Hatem S.N. Circ. Res. 104:758-769(2009) [PubMed: 19213956] [Abstract] Cited for: INTERACTION WITH DLG1.
[9]	"Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1." Scannevin R.H., Wang K., Jow F., Megules J., Kopsco D.C., Edris W., Carroll K.C., Lu Q., Xu W., Xu Z., Katz A.H., Olland S., Lin L., Taylor M., Stahl M., Malakian K., Somers W., Mosyak L. , Bowlby M.R., Chanda P., Rhodes K.J. Neuron 41:587-598(2004) [PubMed: 14980207] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 29-143, INTERACTION WITH KCNIP1.
[10]	"Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits." Wang H., Yan Y., Liu Q., Huang Y., Shen Y., Chen L., Chen Y., Yang Q., Hao Q., Wang K., Chai J. Nat. Neurosci. 10:32-39(2007) [PubMed: 17187064] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 6-145 IN COMPLEX WITH KCNIP1, SUBUNIT.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-94.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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, AL049557, AL450997 Genomic DNA. Translation: CAI16956.1.
AL450997, AL049557, AL512665 Genomic DNA. Translation: CAI19096.1.
AL049557, AL450997, AL512665 Genomic DNA. Translation: CAI22711.1.

IPI

IPI00383327.
IPI00383328.

RefSeq

NP_004971.2. NM_004980.4.
NP_751948.1. NM_172198.2.

UniGene

Hs.666367.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S1G	X-ray	2.60	A/B	29-143	[»]
2NZ0	X-ray	3.20	B/D	6-145	[»]

ProteinModelPortal

Q9UK17.

SMR

Q9UK17. Positions 6-413.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9UK17.

PTM databases

PhosphoSite

Q9UK17.

Polymorphism databases

DMDM

92090984.

Proteomic databases

PRIDE

Q9UK17.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315987; ENSP00000319591; ENSG00000171385.

GeneID

3752.

KEGG

hsa:3752.

NMPDR

fig|9606.3.peg.1710.

UCSC

uc001ebu.1. human.
uc001ebv.1. human.

Organism-specific databases

CTD

3752.

GeneCards

GC01M112313.

H-InvDB

HIX0028524.

HGNC

HGNC:6239. KCND3.

HPA

HPA029452.

MIM

605411. gene.

neXtProt

NX_Q9UK17.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06939.

GeneTree

ENSGT00580000081431.

HOVERGEN

HBG106687.

InParanoid

Q9UK17.

OMA

MGTPEEE.

OrthoDB

EOG4HMJ8X.

PhylomeDB

Q9UK17.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q9UK17.

Bgee

Q9UK17.

CleanEx

HS_KCND3.

Genevestigator

Q9UK17.

GermOnline

ENSG00000171385. Homo sapiens.

Family and domain databases

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR005821. Ion_trans.
IPR003091. K_chnl.
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.
IPR003131. K_chnl_volt-dep_Kv_tetra.
IPR021645. Shal-type.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.

KO

K04893.

Pfam

PF11879. DUF3399. 1 hit.
PF00520. Ion_trans. 1 hit.
PF02214. K_tetra. 1 hit.
PF11601. Shal-type. 1 hit.
[Graphical view]

PRINTS

PR00169. KCHANNEL.
PR01518. KV43CHANNEL.
PR01491. KVCHANNEL.
PR01497. SHALCHANNEL.

SMART

SM00225. BTB. 1 hit.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.

ProtoNet

Search...

Other

NextBio

14691.

SOURCE

Search...

Entry information

Entry name

KCND3_HUMAN

Accession

Primary (citable) accession number: Q9UK17
Secondary accession number(s): O60576 , O60577, Q5T0M0, Q9UH85, Q9UH86, Q9UK16

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	March 7, 2006
Last modified:	January 25, 2012
This is version 105 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.