KCIP2_MOUSE
ID KCIP2_MOUSE Reviewed; 270 AA.
AC Q9JJ69; Q6DTJ2; Q8K1T8; Q8K1T9; Q8K1U0; Q8VHN4; Q8VHN5; Q8VHN6; Q9JJ68;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Kv channel-interacting protein 2;
DE Short=KChIP2;
DE AltName: Full=A-type potassium channel modulatory protein 2;
DE AltName: Full=Potassium channel-interacting protein 2;
GN Name=Kcnip2; Synonyms=Kchip2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND TISSUE SPECIFICITY.
RC TISSUE=Aorta, Brain, Heart, and Stomach;
RX PubMed=11263977; DOI=10.1006/bbrc.2001.4558;
RA Ohya S., Morohashi Y., Muraki K., Tomita T., Watanabe M., Iwatsubo T.,
RA Imaizumi Y.;
RT "Molecular cloning and expression of the novel splice variants of K(+)
RT channel-interacting protein 2.";
RL Biochem. Biophys. Res. Commun. 282:96-102(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=BALB/cJ;
RX PubMed=11747815; DOI=10.1016/s0092-8674(01)00588-8;
RA Kuo H.-C., Cheng C.-F., Clark R.B., Lin J.J.C., Lin J.L.C., Hoshijima M.,
RA Nguyen-Tran V.T.B., Gu Y., Ikeda Y., Chu P.-H., Ross J. Jr., Giles W.R.,
RA Chien K.R.;
RT "A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a
RT complete loss of I(to) and confers susceptibility to ventricular
RT tachycardia.";
RL Cell 107:801-813(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Xia K.U., Fang H.Y., Zhong X.Y., Xia J.H., Zhang Z.H.;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-270 (ISOFORMS 1; 2 AND 3).
RA Franz O., Soloviev M., Roeper J.;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH KCND2 AND KCND3.
RX PubMed=11909823; DOI=10.1161/01.res.0000012664.05949.e0;
RA Guo W., Li H., Aimond F., Johns D.C., Rhodes K.J., Trimmer J.S.,
RA Nerbonne J.M.;
RT "Role of heteromultimers in the generation of myocardial transient outward
RT K+ currents.";
RL Circ. Res. 90:586-593(2002).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15363885; DOI=10.1016/j.molbrainres.2004.06.024;
RA Xiong H., Kovacs I., Zhang Z.;
RT "Differential distribution of KChIPs mRNAs in adult mouse brain.";
RL Brain Res. Mol. Brain Res. 128:103-111(2004).
RN [7]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19713751; DOI=10.4161/chan.3.4.9553;
RA Marionneau C., LeDuc R.D., Rohrs H.W., Link A.J., Townsend R.R.,
RA Nerbonne J.M.;
RT "Proteomic analyses of native brain K(V)4.2 channel complexes.";
RL Channels 3:284-294(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH KCND2.
RX PubMed=20943905; DOI=10.1523/jneurosci.2487-10.2010;
RA Norris A.J., Foeger N.C., Nerbonne J.M.;
RT "Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in
RT the generation of Kv4-encoded IA channels in cortical pyramidal neurons.";
RL J. Neurosci. 30:13644-13655(2010).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23713033; DOI=10.1113/jphysiol.2013.255836;
RA Foeger N.C., Wang W., Mellor R.L., Nerbonne J.M.;
RT "Stabilization of Kv4 protein by the accessory K(+) channel interacting
RT protein 2 (KChIP2) subunit is required for the generation of native
RT myocardial fast transient outward K(+) currents.";
RL J. Physiol. (Lond.) 591:4149-4166(2013).
CC -!- FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly
CC inactivating A-type potassium channels. Modulates channel density,
CC inactivation kinetics and rate of recovery from inactivation in a
CC calcium-dependent and isoform-specific manner (PubMed:20943905,
CC PubMed:23713033). In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3
CC currents. Involved in KCND2 and KCND3 trafficking to the cell surface.
CC Essential for the expression of I(To) currents in the heart
CC (PubMed:11747815, PubMed:23713033). Required for normal protein levels
CC of KCND2 in the heart ventricle (PubMed:23713033).
CC {ECO:0000250|UniProtKB:Q9NS61, ECO:0000269|PubMed:11747815,
CC ECO:0000269|PubMed:20943905, ECO:0000269|PubMed:23713033}.
CC -!- SUBUNIT: Component of heteromultimeric potassium channels
CC (PubMed:19713751, PubMed:20943905). Identified in potassium channel
CC complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3,
CC KCNIP4, DPP6 and DPP10 (PubMed:19713751). The KCND2-KCNIP2 channel
CC complex contains four KCND2 and four KCNIP2 subunits. Probably part of
CC a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. At least
CC isoform 2 and isoform 3 can self-associate to form homodimers and
CC homotetramers. Isoform 3 interacts with KCNIP1 in a calcium-dependent
CC manner (By similarity). Interacts with KCND2 (PubMed:20943905). Isoform
CC 1 and isoform 3 interact with KCND3 isoform 1.
CC {ECO:0000250|UniProtKB:Q9NS61, ECO:0000269|PubMed:11909823,
CC ECO:0000269|PubMed:19713751, ECO:0000269|PubMed:20943905}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9JM59};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q9JM59}. Note=Detected on lipid
CC rafts (By similarity). {ECO:0000250|UniProtKB:Q9JM59}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=A, KChIP2a, KCHIP2B, KChIP2L;
CC IsoId=Q9JJ69-1; Sequence=Displayed;
CC Name=2; Synonyms=B, KChIP2b, KCHIP2C;
CC IsoId=Q9JJ69-2; Sequence=VSP_015061;
CC Name=3; Synonyms=KCHIP2A, KChIP2b, KChIP2c, KChIP2S;
CC IsoId=Q9JJ69-3; Sequence=VSP_015060;
CC Name=4;
CC IsoId=Q9JJ69-4; Sequence=VSP_015059;
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:23713033). Expressed in brain. Highly expressed in layer IV of
CC the cerebral cortex and in striatum and hippocampus, but expressed at
CC low levels in cerebellum. Also expressed in heart. According to
CC PubMed:11747815 expressed in heart at much higher levels than in brain
CC with a preferential expression in the myocardium.
CC {ECO:0000269|PubMed:11263977, ECO:0000269|PubMed:11747815,
CC ECO:0000269|PubMed:15363885, ECO:0000269|PubMed:23713033}.
CC -!- PTM: Palmitoylated. Palmitoylation enhances association with the plasma
CC membrane. {ECO:0000250|UniProtKB:Q9JM59}.
CC -!- DISRUPTION PHENOTYPE: Mice appear healthy and show no signs of cardiac
CC dysmorphogenesis, contractile dysfunction, hypertrophy, or heart
CC failure but are highly susceptible to the induction of polymorphic
CC ventricular tachycardia, including arrhythmia (PubMed:11747815,
CC PubMed:23713033). Myocytes show a complete and selective loss of I(To)
CC current in the heart (PubMed:11747815, PubMed:23713033). This is due to
CC the loss of KCND2 protein in the heart ventricles (PubMed:23713033).
CC {ECO:0000269|PubMed:11747815, ECO:0000269|PubMed:23713033}.
CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}.
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DR EMBL; AB044570; BAA96738.1; -; mRNA.
DR EMBL; AB044571; BAA96739.1; -; mRNA.
DR EMBL; AF439339; AAL32044.1; -; mRNA.
DR EMBL; AF439340; AAL32045.1; -; mRNA.
DR EMBL; AF439341; AAL32046.1; -; mRNA.
DR EMBL; AY647241; AAT68467.1; -; mRNA.
DR EMBL; AJ278535; CAC82023.1; -; mRNA.
DR EMBL; AJ278536; CAC82024.1; -; mRNA.
DR EMBL; AJ278537; CAC82026.1; -; mRNA.
DR CCDS; CCDS29868.1; -. [Q9JJ69-3]
DR CCDS; CCDS38004.1; -. [Q9JJ69-1]
DR CCDS; CCDS50453.1; -. [Q9JJ69-2]
DR CCDS; CCDS70955.1; -. [Q9JJ69-4]
DR RefSeq; NP_001263287.1; NM_001276358.1. [Q9JJ69-4]
DR RefSeq; NP_109641.2; NM_030716.3.
DR RefSeq; NP_663749.1; NM_145703.2.
DR RefSeq; NP_663750.1; NM_145704.2.
DR RefSeq; XP_017173804.1; XM_017318315.1.
DR AlphaFoldDB; Q9JJ69; -.
DR SMR; Q9JJ69; -.
DR BioGRID; 219843; 2.
DR ComplexPortal; CPX-3261; Kv4.2-KChIP2 channel complex.
DR STRING; 10090.ENSMUSP00000125142; -.
DR iPTMnet; Q9JJ69; -.
DR PhosphoSitePlus; Q9JJ69; -.
DR MaxQB; Q9JJ69; -.
DR PaxDb; Q9JJ69; -.
DR PRIDE; Q9JJ69; -.
DR ProteomicsDB; 301763; -. [Q9JJ69-1]
DR ProteomicsDB; 301764; -. [Q9JJ69-2]
DR ProteomicsDB; 301765; -. [Q9JJ69-3]
DR ProteomicsDB; 301766; -. [Q9JJ69-4]
DR ABCD; Q9JJ69; 2 sequenced antibodies.
DR Antibodypedia; 17919; 435 antibodies from 30 providers.
DR DNASU; 80906; -.
DR Ensembl; ENSMUST00000086993; ENSMUSP00000084215; ENSMUSG00000025221. [Q9JJ69-4]
DR GeneID; 80906; -.
DR KEGG; mmu:80906; -.
DR CTD; 30819; -.
DR MGI; MGI:2135916; Kcnip2.
DR VEuPathDB; HostDB:ENSMUSG00000025221; -.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000157798; -.
DR InParanoid; Q9JJ69; -.
DR OMA; ELWEVVI; -.
DR OrthoDB; 1271942at2759; -.
DR Reactome; R-MMU-5576894; Phase 1 - inactivation of fast Na+ channels.
DR BioGRID-ORCS; 80906; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Kcnip2; mouse.
DR PRO; PR:Q9JJ69; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9JJ69; protein.
DR Bgee; ENSMUSG00000025221; Expressed in interventricular septum and 160 other tissues.
DR ExpressionAtlas; Q9JJ69; baseline and differential.
DR Genevisible; Q9JJ69; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005250; F:A-type (transient outward) potassium channel activity; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015459; F:potassium channel regulator activity; IMP:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0045163; P:clustering of voltage-gated potassium channels; ISO:MGI.
DR GO; GO:0086009; P:membrane repolarization; ISO:MGI.
DR GO; GO:1903766; P:positive regulation of potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IMP:UniProtKB.
DR CDD; cd00051; EFh; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR028846; Recoverin.
DR PANTHER; PTHR23055; PTHR23055; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 3.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Ion channel; Ion transport;
KW Lipoprotein; Membrane; Metal-binding; Palmitate; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Repeat;
KW Transport; Voltage-gated channel.
FT CHAIN 1..270
FT /note="Kv channel-interacting protein 2"
FT /id="PRO_0000073822"
FT DOMAIN 81..137
FT /note="EF-hand 1; degenerate"
FT /evidence="ECO:0000305"
FT DOMAIN 140..175
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 176..211
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 224..259
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 257..270
FT /note="Interaction with KCND2"
FT /evidence="ECO:0000250|UniProtKB:Q8R426"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 157
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 159
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 164
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 191
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 241
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM59"
FT LIPID 45
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM59"
FT LIPID 46
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM59"
FT VAR_SEQ 1..73
FT /note="MRGQGRKESLSDSRDLDGSYDQLTGHPPGPSKKALKQRFLKLLPCCGPQALP
FT SVSETLAAPASLRPHRPRPLD -> MNRCPRRCRSPLGQAARSLYQLVTGSLS (in
FT isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_015059"
FT VAR_SEQ 25..74
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11263977,
FT ECO:0000303|PubMed:11747815, ECO:0000303|Ref.4"
FT /id="VSP_015060"
FT VAR_SEQ 57..75
FT /note="TLAAPASLRPHRPRPLDPD -> N (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11747815, ECO:0000303|Ref.4"
FT /id="VSP_015061"
FT CONFLICT 12
FT /note="D -> E (in Ref. 2; AAL32044/AAL32045/AAL32046)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="S -> T (in Ref. 1; BAA96738)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="A -> V (in Ref. 1; BAA96738)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="D -> G (in Ref. 4; CAC82023)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="R -> K (in Ref. 1; BAA96738/BAA96739)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="N -> T (in Ref. 1; BAA96738/BAA96739)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="I -> V (in Ref. 1; BAA96738/BAA96739)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="N -> S (in Ref. 1; BAA96738/BAA96739)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="E -> G (in Ref. 4; CAC82024)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="Q -> K (in Ref. 1; BAA96738/BAA96739)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 270 AA; 30946 MW; DB5AC273B2C0F667 CRC64;
MRGQGRKESL SDSRDLDGSY DQLTGHPPGP SKKALKQRFL KLLPCCGPQA LPSVSETLAA
PASLRPHRPR PLDPDSVEDE FELSTVCHRP EGLEQLQEQT KFTRRELQVL YRGFKNECPS
GIVNEENFKQ IYSQFFPQGD SSNYATFLFN AFDTNHDGSV SFEDFVAGLS VILRGTIDDR
LNWAFNLYDL NKDGCITKEE MLDIMKSIYD MMGKYTYPAL REEAPREHVE SFFQKMDRNK
DGVVTIEEFI ESCQQDENIM RSMQLFDNVI
