Q63881 (KCND2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily D member 2

Alternative name(s):
RK5
Shal1
Voltage-gated potassium channel subunit Kv4.2

Gene names

Name:

Kcnd2

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	630 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
Subunit structure	Homotetramer or heterotetramer with KCND1 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. The KCND2-KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits. Interacts with FLNA and FLNC By similarity. Interacts with DPP6, DPP10, DLG4, NCS1/FREQ and DLG1. Ref.3 Ref.4 Ref.5 Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell projection › dendrite. Note: Interaction with DPP6, DLG4 or NCS1/FREQ may increase cell surface expression. Localized preferentially to the dendrites of pyramidal cells. Ref.8
Tissue specificity	Highly expressed in heart and throughout the brain, with similar levels in cortex and hypothalamus, and much higher levels in hippocampus, dentate gyrus and the habenular nucleus of the thalamus. Detected at similar levels in heart atrium and ventricle. Detected in aorta, cardiac and smooth muscle. Ref.1 Ref.2
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	Phosphorylated on serine and threonine residues By similarity. Ref.7
Sequence similarities	Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily. [View classification]
Sequence caution	The sequence AAA40929.1 differs from that shown. Reason: Frameshift at position 477.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Cell projection Membrane
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 heterooligomerization Inferred from direct assay PubMed 16123112. Source: RGD protein homooligomerization Inferred from electronic annotation. Source: InterPro regulation of action potential Inferred from mutant phenotype PubMed 16141270. Source: RGD
Cellular_component	neuronal cell body Inferred from direct assay PubMed 15736227PubMed 20849929. Source: RGD perinuclear endoplasmic reticulum Inferred from direct assay PubMed 12967630. Source: RGD postsynaptic density Inferred from direct assay PubMed 17635915. Source: RGD voltage-gated potassium channel complex Inferred from direct assay Ref.10PubMed 16123112. Source: RGD
Molecular_function	A-type (transient outward) potassium channel activity Inferred from mutant phenotype PubMed 16123112. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Inferred from direct assay Ref.15. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 630

630

Potassium voltage-gated channel subfamily D member 2

PRO_0000054067

Regions

Topological domain

1 – 183

183

Cytoplasmic Potential

Transmembrane

184 – 204

21

Helical; Name=Segment S1; Potential

Transmembrane

225 – 245

21

Helical; Name=Segment S2; Potential

Topological domain

246 – 259

14

Cytoplasmic Potential

Transmembrane

260 – 280

21

Helical; Name=Segment S3; Potential

Transmembrane

290 – 310

21

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

Topological domain

311 – 323

13

Cytoplasmic Potential

Transmembrane

324 – 344

21

Helical; Name=Segment S5; Potential

Intramembrane

363 – 383

21

Pore-forming; Name=Segment H5; Potential

Transmembrane

385 – 405

21

Helical; Name=Segment S6; Potential

Topological domain

406 – 630

225

Cytoplasmic Potential

Region

2 – 20

19

Interaction with KCNIP2 By similarity

Region

7 – 11

5

Interaction with KCNIP1

Region

71 – 90

20

Interaction with KCNIP1

Region

474 – 489

16

Mediates dendritic targeting

Motif

370 – 375

6

Selectivity filter By similarity

Sites

Metal binding

105

1

Zinc By similarity

Metal binding

132

1

Zinc By similarity

Metal binding

133

1

Zinc By similarity

Amino acid modifications

Modified residue

38

1

Phosphothreonine By similarity

Modified residue

548

1

Phosphoserine By similarity

Modified residue

552

1

Phosphoserine Ref.7

Modified residue

602

1

Phosphothreonine By similarity

Modified residue

607

1

Phosphothreonine By similarity

Modified residue

616

1

Phosphoserine By similarity

Experimental info

Mutagenesis

7 – 11

5

Missing: Greatly reduces interaction with KCNIP1. Ref.11 Ref.15

Mutagenesis

8

1

W → A: Abolishes interaction with KCNP1; when associated with A-11. Ref.15

Mutagenesis

11

1

F → A: Abolishes interaction with KCNP1; when associated with A-8. Ref.15

Mutagenesis

66

1

L → R: Abolishes expression. Ref.14

Mutagenesis

71

1

E → K: Abolishes interaction with KCNIP1. Ref.11

Mutagenesis

73

1

D → M: Abolishes interaction with KCNIP1. Ref.11

Mutagenesis

74

1

F → R: Abolishes interaction with KCNIP1. Ref.11

Mutagenesis

79

1

E → L or R: Abolishes interaction with KCNIP1. Ref.11

Mutagenesis

93

1

R → A: Greatly reduces expression and changes multimerization. Ref.14

Mutagenesis

481 – 482

2

Missing: Loss of dendritic targeted expression. Ref.8

Mutagenesis

627 – 630

4

Missing: Abolishes interaction with DLG4. Ref.6

Secondary structure

1

.

.

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.

.

.

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.

.

.

.

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.

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.

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630

Helix Strand Turn

Details...

Helix

1 – 6

6

Helix

9 – 17

9

Beta strand

43 – 47

5

Beta strand

50 – 54

5

Helix

56 – 60

5

Beta strand

64 – 66

3

Helix

70 – 75

6

Helix

78 – 80

3

Beta strand

81 – 85

5

Turn

89 – 91

3

Helix

92 – 101

10

Helix

112 – 122

11

Helix

131 – 145

15

Sequences

	Sequence		Length	Mass (Da)
	Q63881 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: FDE57E8A5113BABF	FASTA	630	70,549
	10 20 30 40 50 60 MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE 70 80 90 100 110 120 RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA 130 140 150 160 170 180 FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDNTGES ALPTMTARQR VWRAFENPHT 190 200 210 220 230 240 STMALVFYYV TGFFIAVSVI ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF 250 260 270 280 290 300 TVEYLLRLAA APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI 310 320 330 340 350 360 FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS ASKFTSIPAA 370 380 390 400 410 420 FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL PVPVIVSNFS RIYHQNQRAD 430 440 450 460 470 480 KRRAQKKARL ARIRAAKSGS ANAYMQSKRN GLLSNQLQSS EDEPAFVSKS GSSFETQHHH 490 500 510 520 530 540 LLHCLEKTTN HEFVDEQVFE ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKSFRI 550 560 570 580 590 600 PNANVSGSHR GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI 610 620 630 PTPPVTTPEG DDRPESPEYS GGNIVRVSAL

References

[1]	"Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel." Baldwin T.J., Tsaur M.-L., Lopez G.A., Jan Y.N., Jan L.Y. Neuron 7:471-483(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Hippocampus.
[2]	"Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart." Roberds S.L., Tamkun M.M. Proc. Natl. Acad. Sci. U.S.A. 88:1798-1802(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Heart.
[3]	"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.
[4]	"A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents." Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B., Coetzee W.A. Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP1 AND NCS1.
[5]	"Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4." Morohashi Y., Hatano N., Ohya S., Takikawa R., Watabiki T., Takasugi N., Imaizumi Y., Tomita T., Iwatsubo T. J. Biol. Chem. 277:14965-14975(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP4.
[6]	"Cell surface targeting and clustering interactions between heterologously expressed PSD-95 and the Shal voltage-gated potassium channel, Kv4.2." Wong W., Newell E.W., Jugloff D.G.M., Jones O.T., Schlichter L.C. J. Biol. Chem. 277:20423-20430(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF 627-VAL--LEU-630, INTERACTION WITH DLG4.
[7]	"A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels." Shibata R., Misonou H., Campomanes C.R., Anderson A.E., Schrader L.A., Doliveira L.C., Carroll K.I., Sweatt J.D., Rhodes K.J., Trimmer J.S. J. Biol. Chem. 278:36445-36454(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-552.
[8]	"An evolutionarily conserved dileucine motif in Shal K+ channels mediates dendritic targeting." Rivera J.F., Ahmad S., Quick M.W., Liman E.R., Arnold D.B. Nat. Neurosci. 6:243-250(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, DENDRITIC TARGETING REGION, MUTAGENESIS OF 481-LEU--LEU-482.
[9]	"The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels." Nadal M.S., Ozaita A., Amarillo Y., Vega-Saenz de Miera E., Ma Y., Mo W., Goldberg E.M., Misumi Y., Ikehara Y., Neubert T.A., Rudy B. Neuron 37:449-461(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPP6.
[10]	"KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain." Rhodes K.J., Carroll K.I., Sung M.A., Doliveira L.C., Monaghan M.M., Burke S.L., Strassle B.W., Buchwalder L., Menegola M., Cao J., An W.F., Trimmer J.S. J. Neurosci. 24:7903-7915(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP1 AND KCNIP3.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP1, MUTAGENESIS OF 7-ALA--PHE-11; GLU-71; ASP-73; PHE-74 AND GLU-79.
[12]	"DPP10 modulates Kv4-mediated A-type potassium channels." Zagha E., Ozaita A., Chang S.Y., Nadal M.S., Lin U., Saganich M.J., McCormack T., Akinsanya K.O., Qi S.Y., Rudy B. J. Biol. Chem. 280:18853-18861(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPP6 AND DPP10.
[13]	"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.
[14]	"Determining the basis of channel-tetramerization specificity by X-ray crystallography and a sequence-comparison algorithm: family values (FamVal)." Nanao M.H., Zhou W., Pfaffinger P.J., Choe S. Proc. Natl. Acad. Sci. U.S.A. 100:8670-8675(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 42-146, MUTAGENESIS OF LEU-66 AND ARG-93.
[15]	"Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels." Zhou W., Qian Y., Kunjilwar K., Pfaffinger P.J., Choe S. Neuron 41:573-586(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-30, INTERACTION WITH KCNIP1; KCNIP2 AND KCNIP3, MUTAGENESIS OF TRP-8 AND PHE-11.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S64320 mRNA. Translation: AAB19939.1.
M59980 mRNA. Translation: AAA40929.1. Frameshift.

IPI

IPI00394218.

PIR

I57681.
JU0271.

RefSeq

NP_113918.2. NM_031730.2.

UniGene

Rn.87841.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NN7	X-ray	2.10	A	42-146	[»]
1S6C	X-ray	2.00	B	1-30	[»]

ProteinModelPortal

Q63881.

SMR

Q63881. Positions 3-146.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q63881. 2 interactions.

MINT

MINT-104113.

STRING

10116.ENSRNOP00000039227.

PTM databases

PhosphoSite

Q63881.

Proteomic databases

PaxDb

Q63881.

PRIDE

Q63881.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

65180.

KEGG

rno:65180.

UCSC

RGD:68393. rat.

Organism-specific databases

CTD

3751.

RGD

68393. Kcnd2.

Phylogenomic databases

eggNOG

COG1226.

HOGENOM

HOG000231013.

HOVERGEN

HBG106687.

InParanoid

Q63881.

KO

K04892.

OrthoDB

EOG4HMJ8X.

Gene expression databases

Genevestigator

Q63881.

GermOnline

ENSRNOG00000029610. 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.
IPR004055. K_chnl_volt-dep_Kv4.2.
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.
PR01517. KV42CHANNEL.
PR01491. KVCHANNEL.
PR01497. SHALCHANNEL.

SMART

SM00225. BTB. 1 hit.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL1075227.

EvolutionaryTrace

Q63881.

NextBio

614080.

Entry information

Entry name

KCND2_RAT

Accession

Primary (citable) accession number: Q63881
Secondary accession number(s): Q00090, Q99249

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program