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Protein

Kv channel-interacting protein 2

Gene

Kcnip2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner (PubMed:20943905, PubMed:23713033). In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and KCND3 trafficking to the cell surface. Essential for the expression of I(To) currents in the heart (PubMed:11747815, PubMed:23713033). Required for normal protein levels of KCND2 in the heart ventricle (PubMed:23713033).By similarity3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi189 – 200121PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi237 – 248122PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Calcium, Metal-binding, Potassium

Names & Taxonomyi

Protein namesi
Recommended name:
Kv channel-interacting protein 2
Short name:
KChIP2
Alternative name(s):
A-type potassium channel modulatory protein 2
Potassium channel-interacting protein 2
Gene namesi
Name:Kcnip2
Synonyms:Kchip2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2135916. Kcnip2.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity

  • Note: Detected on lipid rafts (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice appear healthy and show no signs of cardiac dysmorphogenesis, contractile dysfunction, hypertrophy, or heart failure but are highly susceptible to the induction of polymorphic ventricular tachycardia, including arrhythmia (PubMed:11747815, PubMed:23713033). Myocytes show a complete and selective loss of I(To) current in the heart (PubMed:11747815, PubMed:23713033). This is due to the loss of KCND2 protein in the heart ventricles (PubMed:23713033).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 270270Kv channel-interacting protein 2PRO_0000073822Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91PhosphoserineBy similarity
Lipidationi45 – 451S-palmitoyl cysteineBy similarity
Lipidationi46 – 461S-palmitoyl cysteineBy similarity

Post-translational modificationi

Palmitoylated. Palmitoylation enhances association with the plasma membrane.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ9JJ69.
PaxDbiQ9JJ69.
PRIDEiQ9JJ69.

PTM databases

PhosphoSiteiQ9JJ69.

Expressioni

Tissue specificityi

Detected in brain (at protein level) (PubMed:23713033). Expressed in brain. Highly expressed in layer IV of the cerebral cortex and in striatum and hippocampus, but expressed at low levels in cerebellum. Also expressed in heart. According to PubMed:11747815 expressed in heart at much higher levels than in brain with a preferential expression in the myocardium.4 Publications

Gene expression databases

BgeeiQ9JJ69.
CleanExiMM_KCNIP2.
ExpressionAtlasiQ9JJ69. baseline and differential.
GenevisibleiQ9JJ69. MM.

Interactioni

Subunit structurei

Component of heteromultimeric potassium channels (PubMed:19713751, PubMed:20943905). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). The KCND2-KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. At least isoform 2 and isoform 3 can self-associate to form homodimers and homotetramers. Isoform 3 interacts with KCNIP1 in a calcium-dependent manner (By similarity). Interacts with KCND2 (PubMed:20943905). Isoform 1 and isoform 3 interact with KCND3 isoform 1.By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000125142.

Structurei

3D structure databases

ProteinModelPortaliQ9JJ69.
SMRiQ9JJ69. Positions 28-64, 90-270.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 13757EF-hand 1; degeneratePROSITE-ProRule annotationAdd
BLAST
Domaini140 – 17536EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini176 – 21136EF-hand 3PROSITE-ProRule annotationAdd
BLAST
Domaini224 – 25936EF-hand 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni257 – 27014Interaction with KCND2By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the recoverin family.Curated
Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOVERGENiHBG108179.
InParanoidiQ9JJ69.
OMAiMNRCPRR.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR029532. KCNIP2.
IPR028846. Recoverin.
[Graphical view]
PANTHERiPTHR23055. PTHR23055. 1 hit.
PTHR23055:SF65. PTHR23055:SF65. 1 hit.
PfamiPF13499. EF-hand_7. 1 hit.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JJ69-1) [UniParc]FASTAAdd to basket

Also known as: A, KChIP2a, KCHIP2B, KChIP2L

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
MRGQGRKESL SDSRDLDGSY DQLTGHPPGP SKKALKQRFL KLLPCCGPQA
60 70 80 90 100
LPSVSETLAA PASLRPHRPR PLDPDSVEDE FELSTVCHRP EGLEQLQEQT
110 120 130 140 150
KFTRRELQVL YRGFKNECPS GIVNEENFKQ IYSQFFPQGD SSNYATFLFN
160 170 180 190 200
AFDTNHDGSV SFEDFVAGLS VILRGTIDDR LNWAFNLYDL NKDGCITKEE
210 220 230 240 250
MLDIMKSIYD MMGKYTYPAL REEAPREHVE SFFQKMDRNK DGVVTIEEFI
260 270
ESCQQDENIM RSMQLFDNVI
Length:270
Mass (Da):30,946
Last modified:August 16, 2005 - v2
Checksum:iDB5AC273B2C0F667
GO
Isoform 2 (identifier: Q9JJ69-2) [UniParc]FASTAAdd to basket

Also known as: B, KChIP2b, KCHIP2C

The sequence of this isoform differs from the canonical sequence as follows:
     57-75: TLAAPASLRPHRPRPLDPD → N

Show »
Length:252
Mass (Da):28,997
Checksum:iA54E8D23BDA289ED
GO
Isoform 3 (identifier: Q9JJ69-3) [UniParc]FASTAAdd to basket

Also known as: KCHIP2A, KChIP2b, KChIP2c, KChIP2S

The sequence of this isoform differs from the canonical sequence as follows:
     25-74: Missing.

Show »
Length:220
Mass (Da):25,631
Checksum:iED8BB221099DECCD
GO
Isoform 4 (identifier: Q9JJ69-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MRGQGRKESL...LRPHRPRPLD → MNRCPRRCRSPLGQAARSLYQLVTGSLS

Show »
Length:225
Mass (Da):26,135
Checksum:iC66F919C209473B3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 121D → E in AAL32044 (PubMed:11747815).Curated
Sequence conflicti12 – 121D → E in AAL32045 (PubMed:11747815).Curated
Sequence conflicti12 – 121D → E in AAL32046 (PubMed:11747815).Curated
Sequence conflicti31 – 311S → T in BAA96738 (PubMed:11263977).Curated
Sequence conflicti50 – 501A → V in BAA96738 (PubMed:11263977).Curated
Sequence conflicti75 – 751D → G in CAC82023 (Ref. 4) Curated
Sequence conflicti105 – 1051R → K in BAA96738 (PubMed:11263977).Curated
Sequence conflicti105 – 1051R → K in BAA96739 (PubMed:11263977).Curated
Sequence conflicti143 – 1431N → T in BAA96738 (PubMed:11263977).Curated
Sequence conflicti143 – 1431N → T in BAA96739 (PubMed:11263977).Curated
Sequence conflicti177 – 1771I → V in BAA96738 (PubMed:11263977).Curated
Sequence conflicti177 – 1771I → V in BAA96739 (PubMed:11263977).Curated
Sequence conflicti239 – 2391N → S in BAA96738 (PubMed:11263977).Curated
Sequence conflicti239 – 2391N → S in BAA96739 (PubMed:11263977).Curated
Sequence conflicti248 – 2481E → G in CAC82024 (Ref. 4) Curated
Sequence conflicti255 – 2551Q → K in BAA96738 (PubMed:11263977).Curated
Sequence conflicti255 – 2551Q → K in BAA96739 (PubMed:11263977).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7373MRGQG…PRPLD → MNRCPRRCRSPLGQAARSLY QLVTGSLS in isoform 4. 1 PublicationVSP_015059Add
BLAST
Alternative sequencei25 – 7450Missing in isoform 3. 3 PublicationsVSP_015060Add
BLAST
Alternative sequencei57 – 7519TLAAP…PLDPD → N in isoform 2. 2 PublicationsVSP_015061Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044570 mRNA. Translation: BAA96738.1.
AB044571 mRNA. Translation: BAA96739.1.
AF439339 mRNA. Translation: AAL32044.1.
AF439340 mRNA. Translation: AAL32045.1.
AF439341 mRNA. Translation: AAL32046.1.
AY647241 mRNA. Translation: AAT68467.1.
AJ278535 mRNA. Translation: CAC82023.1.
AJ278536 mRNA. Translation: CAC82024.1.
AJ278537 mRNA. Translation: CAC82026.1.
CCDSiCCDS29868.1. [Q9JJ69-3]
CCDS38004.1. [Q9JJ69-1]
CCDS50453.1. [Q9JJ69-2]
CCDS70955.1. [Q9JJ69-4]
RefSeqiNP_001263287.1. NM_001276358.1. [Q9JJ69-4]
NP_109641.2. NM_030716.3.
NP_663749.1. NM_145703.2.
NP_663750.1. NM_145704.2.
UniGeneiMm.213204.

Genome annotation databases

EnsembliENSMUST00000086993; ENSMUSP00000084215; ENSMUSG00000025221. [Q9JJ69-4]
GeneIDi80906.
KEGGimmu:80906.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044570 mRNA. Translation: BAA96738.1.
AB044571 mRNA. Translation: BAA96739.1.
AF439339 mRNA. Translation: AAL32044.1.
AF439340 mRNA. Translation: AAL32045.1.
AF439341 mRNA. Translation: AAL32046.1.
AY647241 mRNA. Translation: AAT68467.1.
AJ278535 mRNA. Translation: CAC82023.1.
AJ278536 mRNA. Translation: CAC82024.1.
AJ278537 mRNA. Translation: CAC82026.1.
CCDSiCCDS29868.1. [Q9JJ69-3]
CCDS38004.1. [Q9JJ69-1]
CCDS50453.1. [Q9JJ69-2]
CCDS70955.1. [Q9JJ69-4]
RefSeqiNP_001263287.1. NM_001276358.1. [Q9JJ69-4]
NP_109641.2. NM_030716.3.
NP_663749.1. NM_145703.2.
NP_663750.1. NM_145704.2.
UniGeneiMm.213204.

3D structure databases

ProteinModelPortaliQ9JJ69.
SMRiQ9JJ69. Positions 28-64, 90-270.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000125142.

PTM databases

PhosphoSiteiQ9JJ69.

Proteomic databases

MaxQBiQ9JJ69.
PaxDbiQ9JJ69.
PRIDEiQ9JJ69.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000086993; ENSMUSP00000084215; ENSMUSG00000025221. [Q9JJ69-4]
GeneIDi80906.
KEGGimmu:80906.

Organism-specific databases

CTDi30819.
MGIiMGI:2135916. Kcnip2.

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOVERGENiHBG108179.
InParanoidiQ9JJ69.
OMAiMNRCPRR.

Miscellaneous databases

NextBioi350258.
PROiQ9JJ69.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JJ69.
CleanExiMM_KCNIP2.
ExpressionAtlasiQ9JJ69. baseline and differential.
GenevisibleiQ9JJ69. MM.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR029532. KCNIP2.
IPR028846. Recoverin.
[Graphical view]
PANTHERiPTHR23055. PTHR23055. 1 hit.
PTHR23055:SF65. PTHR23055:SF65. 1 hit.
PfamiPF13499. EF-hand_7. 1 hit.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of the novel splice variants of K(+) channel-interacting protein 2."
    Ohya S., Morohashi Y., Muraki K., Tomita T., Watanabe M., Iwatsubo T., Imaizumi Y.
    Biochem. Biophys. Res. Commun. 282:96-102(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY.
    Tissue: Aorta, Brain, Heart and Stomach.
  2. "A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia."
    Kuo H.-C., Cheng C.-F., Clark R.B., Lin J.J.C., Lin J.L.C., Hoshijima M., Nguyen-Tran V.T.B., Gu Y., Ikeda Y., Chu P.-H., Ross J. Jr., Giles W.R., Chien K.R.
    Cell 107:801-813(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
    Strain: BALB/cJ.
  3. Xia K.U., Fang H.Y., Zhong X.Y., Xia J.H., Zhang Z.H.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
  4. Franz O., Soloviev M., Roeper J.
    Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-270 (ISOFORMS 1; 2 AND 3).
  5. "Role of heteromultimers in the generation of myocardial transient outward K+ currents."
    Guo W., Li H., Aimond F., Johns D.C., Rhodes K.J., Trimmer J.S., Nerbonne J.M.
    Circ. Res. 90:586-593(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCND2 AND KCND3.
  6. "Differential distribution of KChIPs mRNAs in adult mouse brain."
    Xiong H., Kovacs I., Zhang Z.
    Brain Res. Mol. Brain Res. 128:103-111(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Proteomic analyses of native brain K(V)4.2 channel complexes."
    Marionneau C., LeDuc R.D., Rohrs H.W., Link A.J., Townsend R.R., Nerbonne J.M.
    Channels 3:284-294(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Heart.
  9. "Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in the generation of Kv4-encoded IA channels in cortical pyramidal neurons."
    Norris A.J., Foeger N.C., Nerbonne J.M.
    J. Neurosci. 30:13644-13655(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCND2.
  10. "Stabilization of Kv4 protein by the accessory K(+) channel interacting protein 2 (KChIP2) subunit is required for the generation of native myocardial fast transient outward K(+) currents."
    Foeger N.C., Wang W., Mellor R.L., Nerbonne J.M.
    J. Physiol. (Lond.) 591:4149-4166(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiKCIP2_MOUSE
AccessioniPrimary (citable) accession number: Q9JJ69
Secondary accession number(s): Q6DTJ2
, Q8K1T8, Q8K1T9, Q8K1U0, Q8VHN4, Q8VHN5, Q8VHN6, Q9JJ68
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: February 17, 2016
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.