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Protein

Potassium voltage-gated channel subfamily D member 2

Gene

Kcnd2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi105 – 1051ZincBy similarity
Metal bindingi132 – 1321ZincBy similarity
Metal bindingi133 – 1331ZincBy similarity

GO - Molecular functioni

  1. A-type (transient outward) potassium channel activity Source: RGD
  2. ion channel activity Source: RGD
  3. metal ion binding Source: UniProtKB-KW
  4. potassium channel activity Source: RGD
  5. protein heterodimerization activity Source: RGD
  6. voltage-gated potassium channel activity Source: RGD

GO - Biological processi

  1. action potential Source: RGD
  2. cellular response to drug Source: RGD
  3. cellular response to mechanical stimulus Source: RGD
  4. potassium ion transmembrane transport Source: GO_Central
  5. potassium ion transport Source: RGD
  6. protein heterooligomerization Source: RGD
  7. protein homooligomerization Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Metal-binding, Potassium, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily D member 2
Alternative name(s):
RK5
Shal1
Voltage-gated potassium channel subunit Kv4.2
Gene namesi
Name:Kcnd2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi68393. Kcnd2.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cell projectiondendrite 1 Publication
Note: Interaction with DPP6, DLG4 or NCS1/FREQ may increase cell surface expression. Localized preferentially to the dendrites of pyramidal cells.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 183183CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei184 – 20421Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Transmembranei225 – 24521Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Topological domaini246 – 25914CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei260 – 28021Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Transmembranei290 – 31021Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
BLAST
Topological domaini311 – 32313CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei324 – 34421Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Intramembranei363 – 38321Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Transmembranei385 – 40521Helical; Name=Segment S6Sequence AnalysisAdd
BLAST
Topological domaini406 – 630225CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. dendrite Source: RGD
  2. dendritic spine Source: RGD
  3. integral component of plasma membrane Source: RGD
  4. neuronal cell body Source: RGD
  5. neuron projection Source: RGD
  6. perinuclear endoplasmic reticulum Source: RGD
  7. plasma membrane Source: RGD
  8. postsynaptic density Source: RGD
  9. potassium channel complex Source: RGD
  10. voltage-gated potassium channel complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi7 – 115Missing: Greatly reduces interaction with KCNIP1. 1 Publication
Mutagenesisi8 – 81W → A: Abolishes interaction with KCNP1; when associated with A-11. 1 Publication
Mutagenesisi11 – 111F → A: Abolishes interaction with KCNP1; when associated with A-8. 1 Publication
Mutagenesisi66 – 661L → R: Abolishes expression. 1 Publication
Mutagenesisi71 – 711E → K: Abolishes interaction with KCNIP1. 1 Publication
Mutagenesisi73 – 731D → M: Abolishes interaction with KCNIP1. 1 Publication
Mutagenesisi74 – 741F → R: Abolishes interaction with KCNIP1. 1 Publication
Mutagenesisi79 – 791E → L or R: Abolishes interaction with KCNIP1. 1 Publication
Mutagenesisi93 – 931R → A: Greatly reduces expression and changes multimerization. 1 Publication
Mutagenesisi481 – 4822Missing: Loss of dendritic targeted expression. 1 Publication
Mutagenesisi627 – 6304Missing: Abolishes interaction with DLG4. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 630630Potassium voltage-gated channel subfamily D member 2PRO_0000054067Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei38 – 381PhosphothreonineBy similarity
Modified residuei552 – 5521Phosphoserine1 Publication
Modified residuei602 – 6021PhosphothreonineBy similarity
Modified residuei607 – 6071PhosphothreonineBy similarity
Modified residuei616 – 6161PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on serine and threonine residues.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63881.
PRIDEiQ63881.

PTM databases

PhosphoSiteiQ63881.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

GenevestigatoriQ63881.

Interactioni

Subunit structurei

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.By similarity10 Publications

Protein-protein interaction databases

BioGridi249292. 2 interactions.
IntActiQ63881. 3 interactions.
MINTiMINT-104113.
STRINGi10116.ENSRNOP00000039227.

Structurei

Secondary structure

630
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1 – 66Combined sources
Helixi9 – 179Combined sources
Beta strandi43 – 475Combined sources
Beta strandi50 – 545Combined sources
Helixi56 – 605Combined sources
Beta strandi64 – 663Combined sources
Helixi70 – 756Combined sources
Helixi78 – 803Combined sources
Beta strandi81 – 855Combined sources
Turni89 – 913Combined sources
Helixi92 – 10110Combined sources
Helixi112 – 12211Combined sources
Helixi131 – 14515Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NN7X-ray2.10A42-146[»]
1S6CX-ray2.00B1-30[»]
ProteinModelPortaliQ63881.
SMRiQ63881. Positions 3-146.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ63881.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 2019Interaction with KCNIP2By similarityAdd
BLAST
Regioni7 – 115Interaction with KCNIP1
Regioni71 – 9020Interaction with KCNIP1Add
BLAST
Regioni474 – 48916Mediates dendritic targetingAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi370 – 3756Selectivity filterBy similarity

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

eggNOGiCOG1226.
HOGENOMiHOG000231013.
HOVERGENiHBG106687.
InParanoidiQ63881.
KOiK04892.
PhylomeDBiQ63881.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
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.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF11879. DUF3399. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11601. Shal-type. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01517. KV42CHANNEL.
PR01491. KVCHANNEL.
PR01497. SHALCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

Q63881-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT
60 70 80 90 100
RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR
110 120 130 140 150
TGKLHYPRHE CISAYDEELA FFGLIPEIIG DCCYEEYKDR RRENAERLQD
160 170 180 190 200
DADTDNTGES ALPTMTARQR VWRAFENPHT STMALVFYYV TGFFIAVSVI
210 220 230 240 250
ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF TVEYLLRLAA
260 270 280 290 300
APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI
310 320 330 340 350
FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS
360 370 380 390 400
ASKFTSIPAA FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL
410 420 430 440 450
PVPVIVSNFS RIYHQNQRAD KRRAQKKARL ARIRAAKSGS ANAYMQSKRN
460 470 480 490 500
GLLSNQLQSS EDEPAFVSKS GSSFETQHHH LLHCLEKTTN HEFVDEQVFE
510 520 530 540 550
ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKSFRI PNANVSGSHR
560 570 580 590 600
GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
610 620 630
PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
Length:630
Mass (Da):70,549
Last modified:November 1, 1996 - v1
Checksum:iFDE57E8A5113BABF
GO

Sequence cautioni

The sequence AAA40929.1 differs from that shown. Reason: Frameshift at position 477. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S64320 mRNA. Translation: AAB19939.1.
M59980 mRNA. Translation: AAA40929.1. Frameshift.
PIRiI57681.
JU0271.
RefSeqiNP_113918.2. NM_031730.2.
UniGeneiRn.87841.

Genome annotation databases

GeneIDi65180.
KEGGirno:65180.
UCSCiRGD:68393. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S64320 mRNA. Translation: AAB19939.1.
M59980 mRNA. Translation: AAA40929.1. Frameshift.
PIRiI57681.
JU0271.
RefSeqiNP_113918.2. NM_031730.2.
UniGeneiRn.87841.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NN7X-ray2.10A42-146[»]
1S6CX-ray2.00B1-30[»]
ProteinModelPortaliQ63881.
SMRiQ63881. Positions 3-146.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249292. 2 interactions.
IntActiQ63881. 3 interactions.
MINTiMINT-104113.
STRINGi10116.ENSRNOP00000039227.

Chemistry

BindingDBiQ63881.
ChEMBLiCHEMBL1075227.
GuidetoPHARMACOLOGYi553.

PTM databases

PhosphoSiteiQ63881.

Proteomic databases

PaxDbiQ63881.
PRIDEiQ63881.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65180.
KEGGirno:65180.
UCSCiRGD:68393. rat.

Organism-specific databases

CTDi3751.
RGDi68393. Kcnd2.

Phylogenomic databases

eggNOGiCOG1226.
HOGENOMiHOG000231013.
HOVERGENiHBG106687.
InParanoidiQ63881.
KOiK04892.
PhylomeDBiQ63881.

Miscellaneous databases

EvolutionaryTraceiQ63881.
NextBioi614080.
PROiQ63881.

Gene expression databases

GenevestigatoriQ63881.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
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.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF11879. DUF3399. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11601. Shal-type. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01517. KV42CHANNEL.
PR01491. KVCHANNEL.
PR01497. SHALCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Publicationsi

  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. 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. Cited for: INTERACTION WITH KCNIP1, MUTAGENESIS OF 7-ALA--PHE-11; GLU-71; ASP-73; PHE-74 AND GLU-79.
  12. 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.

Entry informationi

Entry nameiKCND2_RAT
AccessioniPrimary (citable) accession number: Q63881
Secondary accession number(s): Q00090, Q99249
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 1, 1996
Last modified: February 4, 2015
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.