KCIP2_RAT
ID KCIP2_RAT Reviewed; 270 AA.
AC Q9JM59; Q9JI21; Q9JI22; Q9JI23; Q9JM60;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 147.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), INTERACTION WITH KCND3,
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
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), SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, PALMITOYLATION AT CYS-45 AND CYS-46, AND MUTAGENESIS OF
RP 45-CYS-CYS-46.
RC STRAIN=Sprague-Dawley;
RX PubMed=12006572; DOI=10.1074/jbc.m203651200;
RA Takimoto K., Yang E.-K., Conforti L.;
RT "Palmitoylation of KChIP splicing variants is required for efficient cell
RT surface expression of Kv4.3 channels.";
RL J. Biol. Chem. 277:26904-26911(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH KCND2 AND KCND3, AND TISSUE SPECIFICITY.
RX PubMed=10676964; DOI=10.1038/35000592;
RA An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G.,
RA Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J.;
RT "Modulation of A-type potassium channels by a family of calcium sensors.";
RL Nature 403:553-556(2000).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12646414; DOI=10.1152/ajpcell.00416.2002;
RA Boland L.M., Jiang M., Lee S.Y., Fahrenkrug S.C., Harnett M.T.,
RA O'Grady S.M.;
RT "Functional properties of a brain-specific NH2-terminally spliced modulator
RT of Kv4 channels.";
RL Am. J. Physiol. 285:C161-C170(2003).
RN [6]
RP FUNCTION, INTERACTION WITH KCND2, AND SUBCELLULAR LOCATION.
RX PubMed=16820361; DOI=10.1074/jbc.m604843200;
RA Han W., Nattel S., Noguchi T., Shrier A.;
RT "C-terminal domain of Kv4.2 and associated KChIP2 interactions regulate
RT functional expression and gating of Kv4.2.";
RL J. Biol. Chem. 281:27134-27144(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=24793047; DOI=10.1007/s00424-014-1521-3;
RA Rudakova E., Wagner M., Frank M., Volk T.;
RT "Localization of Kv4.2 and KChIP2 in lipid rafts and modulation of outward
RT K(+) currents by membrane cholesterol content in rat left ventricular
RT myocytes.";
RL Pflugers Arch. 467:299-309(2015).
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:16820361). In
CC vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in
CC KCND2 and KCND3 trafficking to the cell surface. Essential for the
CC expression of I(To) currents in the heart (By similarity). Required for
CC normal protein levels of KCND2 in the heart ventricle (By similarity).
CC {ECO:0000250|UniProtKB:Q9JJ69, ECO:0000250|UniProtKB:Q9NS61,
CC ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:16820361}.
CC -!- SUBUNIT: Component of heteromultimeric potassium channels. Identified
CC in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1,
CC KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). The KCND2-
CC KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits (By
CC similarity). Probably part of a complex consisting of KCNIP1, KCNIP2
CC isoform 3 and KCND2. At least isoform 2 and isoform 3 can self-
CC associate to form homodimers and homotetramers. Isoform 3 interacts
CC with KCNIP1 in a calcium-dependent manner (By similarity). Interacts
CC with KCND2 (PubMed:16820361). Isoform 1 and isoform 3 interact with
CC KCND3 isoform 1. {ECO:0000250|UniProtKB:Q9NS61,
CC ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11263977,
CC ECO:0000269|PubMed:16820361}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11263977,
CC ECO:0000269|PubMed:12006572, ECO:0000269|PubMed:16820361,
CC ECO:0000269|PubMed:24793047}; Lipid-anchor
CC {ECO:0000269|PubMed:12006572}. Note=Detected on lipid rafts.
CC {ECO:0000269|PubMed:24793047}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=B, KCHIP2a, KChIP2L, rKCHIP2b;
CC IsoId=Q9JM59-1; Sequence=Displayed;
CC Name=2; Synonyms=KCHIP2b;
CC IsoId=Q9JM59-2; Sequence=VSP_015065;
CC Name=3; Synonyms=rKCHIP2a, KCHIP2L;
CC IsoId=Q9JM59-3; Sequence=VSP_015064;
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain and lung. In brain,
CC abundantly expressed in striatum, hippocampus and olfactory bulb,
CC moderately expressed in cerebral cortex and lowly expressed in thalamus
CC and hypothalamus. Isoform 1 is predominant in cerebral cortex, striatum
CC and hippocampus. Isoform 1, isoform 2 and isoform 3 are equally
CC expressed in olfactory bulb. Iisoform 3 is expressed at high levels and
CC isoform 1 at low levels in heart (in PubMed:11263977).
CC {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11263977,
CC ECO:0000269|PubMed:12006572, ECO:0000269|PubMed:12646414}.
CC -!- PTM: Palmitoylated. Palmitoylation enhances association with the plasma
CC membrane. {ECO:0000269|PubMed:12006572}.
CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}.
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DR EMBL; AB040031; BAA92743.1; -; mRNA.
DR EMBL; AB040032; BAA92744.1; -; mRNA.
DR EMBL; AF269283; AAF81755.1; -; mRNA.
DR EMBL; AF269284; AAF81756.1; -; mRNA.
DR EMBL; AF269285; AAF81757.1; -; mRNA.
DR EMBL; BC085905; AAH85905.1; -; mRNA.
DR PIR; JC7631; JC7631.
DR RefSeq; NP_001029133.1; NM_001033961.1. [Q9JM59-3]
DR RefSeq; NP_064479.2; NM_020094.2. [Q9JM59-1]
DR RefSeq; NP_064480.2; NM_020095.2. [Q9JM59-2]
DR RefSeq; XP_008758701.1; XM_008760479.2. [Q9JM59-1]
DR RefSeq; XP_008758702.1; XM_008760480.2. [Q9JM59-2]
DR RefSeq; XP_008758704.1; XM_008760482.2. [Q9JM59-3]
DR RefSeq; XP_017445315.1; XM_017589826.1. [Q9JM59-1]
DR RefSeq; XP_017445321.1; XM_017589832.1. [Q9JM59-2]
DR RefSeq; XP_017445328.1; XM_017589839.1. [Q9JM59-3]
DR AlphaFoldDB; Q9JM59; -.
DR SMR; Q9JM59; -.
DR BioGRID; 248591; 2.
DR CORUM; Q9JM59; -.
DR STRING; 10116.ENSRNOP00000059337; -.
DR iPTMnet; Q9JM59; -.
DR PhosphoSitePlus; Q9JM59; -.
DR SwissPalm; Q9JM59; -.
DR PaxDb; Q9JM59; -.
DR PRIDE; Q9JM59; -.
DR ABCD; Q9JM59; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000024709; ENSRNOP00000024709; ENSRNOG00000018018. [Q9JM59-1]
DR Ensembl; ENSRNOT00000024750; ENSRNOP00000024750; ENSRNOG00000018018. [Q9JM59-3]
DR GeneID; 56817; -.
DR KEGG; rno:56817; -.
DR UCSC; RGD:70887; rat. [Q9JM59-1]
DR CTD; 30819; -.
DR RGD; 70887; Kcnip2.
DR VEuPathDB; HostDB:ENSRNOG00000014152; -.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000157798; -.
DR HOGENOM; CLU_072366_2_2_1; -.
DR InParanoid; Q9JM59; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q9JM59; -.
DR TreeFam; TF318560; -.
DR Reactome; R-RNO-5576894; Phase 1 - inactivation of fast Na+ channels.
DR PRO; PR:Q9JM59; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018018; Expressed in heart and 19 other tissues.
DR ExpressionAtlas; Q9JM59; baseline and differential.
DR Genevisible; Q9JM59; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005250; F:A-type (transient outward) potassium channel activity; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0045163; P:clustering of voltage-gated potassium channels; IDA:RGD.
DR GO; GO:0086009; P:membrane repolarization; ISO:RGD.
DR GO; GO:1903766; P:positive regulation of potassium ion export across plasma membrane; ISO:RGD.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:RGD.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA: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_0000073824"
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:0007744|PubMed:22673903"
FT LIPID 45
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12006572"
FT LIPID 46
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12006572"
FT VAR_SEQ 25..74
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11263977,
FT ECO:0000303|PubMed:12006572, ECO:0000303|PubMed:15489334"
FT /id="VSP_015064"
FT VAR_SEQ 57..75
FT /note="TLAAPASLRPHRPRPLDPD -> N (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12006572"
FT /id="VSP_015065"
FT MUTAGEN 45..46
FT /note="CC->AA,SS: Abolishes plasma membrane localization."
FT /evidence="ECO:0000269|PubMed:12006572"
FT CONFLICT 12
FT /note="E -> D (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="S -> T (in Ref. 1; BAA92744 and 3; AAH85905)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="A -> V (in Ref. 1; BAA92744 and 3; AAH85905)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="R -> K (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="N -> T (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="I -> V (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="S -> N (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="Q -> K (in Ref. 1; BAA92743/BAA92744)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 270 AA; 30933 MW; C797DEC90FDC3B92 CRC64;
MRGQGRKESL SESRDLDGSY DQLTGHPPGP SKKALKQRFL KLLPCCGPQA LPSVSETLAA
PASLRPHRPR PLDPDSVEDE FELSTVCHRP EGLEQLQEQT KFTRRELQVL YRGFKNECPS
GIVNEENFKQ IYSQFFPQGD SSNYATFLFN AFDTNHDGSV SFEDFVAGLS VILRGTIDDR
LSWAFNLYDL NKDGCITKEE MLDIMKSIYD MMGKYTYPAL REEAPREHVE SFFQKMDRNK
DGVVTIEEFI ESCQQDENIM RSMQLFDNVI
