Q62897 (KCND3_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 Ref.3 Ref.4
Subunit structure	Homotetramer or heterotetramer with KCND1 and/or KCND2. Interacts with DLG1. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 By similarity. Ref.7 Ref.9 Ref.11
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell membrane › sarcolemma. Cell projection › dendrite By similarity. Note: Interaction with palmitoylated KCNIP2 and KCNIP3 enhances cell surface expression. Ref.8 Ref.11
Tissue specificity	Highly expressed in brain, in particular in the retrosplenial cortex, medial habenula, anterior thalamus, hippocampus, cerebellum and lateral geniculate and superior colliculus. Highly expressed in heart atrium (at protein level) and throughout the ventricle wall, in lung and vas deferens. Ref.1 Ref.2 Ref.3 Ref.4 Ref.11
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.
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 Cell projection Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Metal-binding Potassium Zinc
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein homooligomerization Inferred from electronic annotation. Source: InterPro
Cellular_component	dendrite Inferred from direct assay PubMed 20849929. Source: RGD integral to plasma membrane Inferred from direct assay PubMed 10325948. Source: RGD neuronal cell body Inferred from direct assay PubMed 15738276PubMed 20849929. Source: RGD perinuclear endoplasmic reticulum Inferred from direct assay PubMed 12967630. Source: RGD sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell voltage-gated potassium channel complex Inferred from electronic annotation. Source: InterPro
Molecular_function	A-type (transient outward) potassium channel activity Inferred from mutant phenotype PubMed 12150935. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q62897-1)

Also known as: Kv4.3 long form;

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: Q62897-2)

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

Isoform 3 (identifier: Q62897-3)

The sequence of this isoform differs from the canonical sequence as follows:
     488-506: Missing.
     608-655: SQITTAIISIPTPPALTPEGESRPPPASPGPNTNIPSITSNVVKVSVL → QDQEQPRGRVVTCKQEEIITLCI

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_0000054071

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

Region

474 – 489

16

Mediates dendritic targeting By similarity

Motif

367 – 372

6

Selectivity filter By similarity

Sites

Metal binding

104

1

Zinc By similarity

Metal binding

131

1

Zinc By similarity

Metal binding

132

1

Zinc By similarity

Amino acid modifications

Modified residue

569

1

Phosphoserine; by CaMK2D Ref.10

Natural variations

Alternative sequence

488 – 506

19

Missing in isoform 2 and isoform 3.

VSP_008831

Alternative sequence

608 – 655

48

SQITT…KVSVL → QDQEQPRGRVVTCKQEEIIT LCI in isoform 3.

VSP_008832

Experimental info

Sequence conflict

124

1

L → H in AAA80459. Ref.3

Sequence conflict

404

1

S → T in AAC52695. Ref.2

Sequence conflict

404

1

S → T in AAK07651. Ref.5

Sequence conflict

569

1

S → T in AAA80459. Ref.3

Sequence conflict

631

1

P → A in AAC52695. Ref.2

Sequence conflict

654

1

V → A in AAB18337. Ref.1

Sequence conflict

654

1

V → A in BAA24525. Ref.4

Secondary structure

1

.

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.

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655

Helix Strand Turn

Details...

Turn

6 – 8

3

Helix

9 – 16

8

Beta strand

41 – 46

6

Beta strand

49 – 54

6

Helix

55 – 59

5

Turn

65 – 67

3

Helix

70 – 74

5

Turn

77 – 80

4

Beta strand

81 – 84

4

Helix

88 – 99

12

Helix

111 – 121

11

Turn

130 – 132

3

Helix

133 – 138

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Kv4.3 long form) [UniParc]. Last modified November 7, 2003. Version 2. Checksum: 26BC512BDE069C09	FASTA	655	73,513
	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 NESENNQESM 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 TRSPSLSSHS 550 560 570 580 590 600 GLTTTCCSRR SKKTTHLPNS NLPATRLRSM QELSTIHIQG SEQPSLTTSR SSLNLKADDG 610 620 630 640 650 LRPNCKTSQI TTAIISIPTP PALTPEGESR PPPASPGPNT NIPSITSNVV KVSVL
	Isoform 2 [UniParc]. Checksum: A2D65B7C3FA5A58A	FASTA	636	71,454
	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 NESENNQESM 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 SGLTTTCCSR RSKKTTHLPN 550 560 570 580 590 600 SNLPATRLRS MQELSTIHIQ GSEQPSLTTS RSSLNLKADD GLRPNCKTSQ ITTAIISIPT 610 620 630 PPALTPEGES RPPPASPGPN TNIPSITSNV VKVSVL
	Isoform 3 [UniParc]. Checksum: 0D6042030E46F4C1	FASTA	611	69,294
	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 NESENNQESM 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 SGLTTTCCSR RSKKTTHLPN 550 560 570 580 590 600 SNLPATRLRS MQELSTIHIQ GSEQPSLTTS RSSLNLKADD GLRPNCKTQD QEQPRGRVVT 610 CKQEEIITLC I

References

[1]	"Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current." Dixon J.E., Shi W., Wang H.-S., McDonald C., Yu H., Wymore R.S., Cohen I.S., McKinnon D. Circ. Res. 79:659-668(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
[2]	"Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain." Serodio P., Vega-Saenz de Miera E., Rudy B. J. Neurophysiol. 75:2174-2179(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Brain.
[3]	"Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha subunit." Tsaur M.-L., Chou C.-C., Shih Y.-H., Wang H.-L. FEBS Lett. 400:215-220(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY. Tissue: Hippocampus.
[4]	"Molecular cloning and tissue distribution of an alternatively spliced variant of an A-type K+ channel alpha-subunit, Kv4.3 in the rat." Ohya S., Tanaka M., Oku T., Asai Y., Watanabe M., Giles W.R., Imaizumi Y. FEBS Lett. 420:47-53(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Smooth muscle and Vas deferens.
[5]	"Remodeling of Kv4.3 potassium channel gene expression under the control of sex hormones." Song M., Helguera G., Eghbali M., Zhu N., Zarei M.M., Olcese R., Toro L., Stefani E. J. Biol. Chem. 276:31883-31890(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Sprague-Dawley. Tissue: Uterus.
[6]	"Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats." Takimoto K., Li D., Hershman K.M., Li P., Jackson E.K., Levitan E.S. Circ. Res. 81:533-539(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 455-606 (ISOFORM 1). Strain: Sprague-Dawley.
[7]	"Modulation of A-type potassium channels by a family of calcium sensors." An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G., Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J. Nature 403:553-556(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP1; KCNIP2 AND KCNIP3.
[8]	"Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels." Takimoto K., Yang E.-K., Conforti L. J. Biol. Chem. 277:26904-26911(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain." Holmqvist M.H., Cao J., Hernandez-Pineda R., Jacobson M.D., Carroll K.I., Sung M.A., Betty M., Ge P., Gilbride K.J., Brown M.E., Jurman M.E., Lawson D., Silos-Santiago I., Xie Y., Covarrubias M., Rhodes K.J., Distefano P.S., An W.F. Proc. Natl. Acad. Sci. U.S.A. 99:1035-1040(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP4.
[10]	"Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II." Sergeant G.P., Ohya S., Reihill J.A., Perrino B.A., Amberg G.C., Imaizumi Y., Horowitz B., Sanders K.M., Koh S.D. Am. J. Physiol. 288:C304-C313(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-569 BY CAMK2D.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DLG1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[12]	"Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer." Pioletti M., Findeisen F., Hura G.L., Minor D.L. Jr. Nat. Struct. Mol. Biol. 13:987-995(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) OF 2-143 IN COMPLEX WITH KCNIP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U75448 mRNA. Translation: AAB18337.1.
U42975 mRNA. Translation: AAC52695.1.
L48619 mRNA. Translation: AAA80459.1.
AB003587 mRNA. Translation: BAA24525.1.
AF334791 mRNA. Translation: AAK07651.1.
U92897 mRNA. Translation: AAB53321.1.

IPI

IPI00389372.
IPI00389373.
IPI00389374.

RefSeq

NP_001257891.1. NM_001270962.1.
NP_001257892.1. NM_001270963.1.
NP_113927.2. NM_031739.3.

UniGene

Rn.10540.
Rn.214215.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I2R	X-ray	3.35	A/B/C/D/I/J/K/L	2-143	[»]

ProteinModelPortal

Q62897.

SMR

Q62897. Positions 3-140.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29245N.

MINT

MINT-103596.

PTM databases

PhosphoSite

Q62897.

Proteomic databases

PaxDb

Q62897.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000019997; ENSRNOP00000019997; ENSRNOG00000014686.
ENSRNOT00000051835; ENSRNOP00000049111; ENSRNOG00000014686.

GeneID

65195.

KEGG

rno:65195.

UCSC

RGD:68394. rat.

Organism-specific databases

CTD

3752.

RGD

68394. Kcnd3.

Phylogenomic databases

eggNOG

COG1226.

GeneTree

ENSGT00630000089518.

HOGENOM

HOG000231013.

HOVERGEN

HBG106687.

InParanoid

Q62897.

KO

K04893.

OrthoDB

EOG4HMJ8X.

Gene expression databases

ArrayExpress

Q62897.

Genevestigator

Q62897.

GermOnline

ENSRNOG00000014686. Rattus norvegicus.

Family and domain databases

Gene3D

3.30.710.10. 1 hit.

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR005821. Ion_trans_dom.
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.
IPR021645. Shal-type.
IPR003131. T1-type_BTB.
[Graphical view]

PANTHER

PTHR11537. PTHR11537. 1 hit.

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

EvolutionaryTrace

Q62897.

NextBio

614128.

Entry information

Entry name

KCND3_RAT

Accession

Primary (citable) accession number: Q62897
Secondary accession number(s): O08723 , P70622, Q63286, Q99P42

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	November 7, 2003
Last modified:	April 3, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program