CSEN_RAT
ID CSEN_RAT Reviewed; 256 AA.
AC Q9JM47;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Calsenilin;
DE AltName: Full=A-type potassium channel modulatory protein 3;
DE AltName: Full=DRE-antagonist modulator;
DE Short=DREAM;
DE AltName: Full=Kv channel-interacting protein 3;
DE Short=KChIP3;
GN Name=Kcnip3; Synonyms=Csen, Dream, Kchip3;
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].
RC TISSUE=Brain;
RA Ohya S., Imaizumi Y.;
RT "A-type potassium channel modulating protein 3.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pituitary;
RA Leclerc G.M., Shorte S.L., Leclerc G.J., Frawley L.S.;
RT "Molecular cloning of the rat DREAM gene.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH KCND2 AND KCND3.
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 [4]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-45 AND CYS-46, AND MUTAGENESIS
RP OF 45-CYS-CYS-46.
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 [5]
RP INTERACTION WITH KCND2.
RX PubMed=15485870; DOI=10.1074/jbc.m409721200;
RA Kunjilwar K., Strang C., DeRubeis D., Pfaffinger P.J.;
RT "KChIP3 rescues the functional expression of Shal channel tetramerization
RT mutants.";
RL J. Biol. Chem. 279:54542-54551(2004).
RN [6]
RP TISSUE SPECIFICITY, AND INTERACTION WITH KCND2.
RX PubMed=15356203; DOI=10.1523/jneurosci.0776-04.2004;
RA Rhodes K.J., Carroll K.I., Sung M.A., Doliveira L.C., Monaghan M.M.,
RA Burke S.L., Strassle B.W., Buchwalder L., Menegola M., Cao J., An W.F.,
RA Trimmer J.S.;
RT "KChIPs and Kv4 alpha subunits as integral components of A-type potassium
RT channels in mammalian brain.";
RL J. Neurosci. 24:7903-7915(2004).
RN [7]
RP INTERACTION WITH KCND2 AND DPP10, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16123112; DOI=10.1113/jphysiol.2005.087858;
RA Jerng H.H., Kunjilwar K., Pfaffinger P.J.;
RT "Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel
RT complexes with ISA-like properties.";
RL J. Physiol. (Lond.) 568:767-788(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP MASS 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).
CC -!- FUNCTION: Calcium-dependent transcriptional repressor that binds to the
CC DRE element of genes including PDYN and FOS. Affinity for DNA is
CC reduced upon binding to calcium and enhanced by binding to magnesium.
CC Seems to be involved in nociception (By similarity).
CC {ECO:0000250|UniProtKB:Q9QXT8}.
CC -!- FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly
CC inactivating A-type potassium channels, such as KCND2/Kv4.2 and
CC KCND3/Kv4.3. Modulates channel expression at the cell membrane, gating
CC characteristics, inactivation kinetics and rate of recovery from
CC inactivation in a calcium-dependent and isoform-specific manner (By
CC similarity). {ECO:0000250|UniProtKB:Q9Y2W7}.
CC -!- FUNCTION: May play a role in the regulation of PSEN2 proteolytic
CC processing and apoptosis. Together with PSEN2 involved in modulation of
CC amyloid-beta formation (By similarity). {ECO:0000250|UniProtKB:Q9Y2W7}.
CC -!- SUBUNIT: Binds to DNA as a homomultimer. Dimerization is induced by
CC binding to calcium. Interacts with the C-terminus of PSEN1 and PSEN2
CC and with PSEN2 CTF subunit. Associates with KCN1. Component of
CC heteromultimeric potassium channels (PubMed:16123112). Identified in
CC potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1,
CC KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with
CC KCND2 and KCND3 (PubMed:10676964). {ECO:0000250|UniProtKB:Q9QXT8,
CC ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:15356203,
CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:16123112}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12006572}. Cell
CC membrane {ECO:0000269|PubMed:12006572, ECO:0000269|PubMed:16123112};
CC Lipid-anchor {ECO:0000269|PubMed:12006572}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:12006572}. Golgi apparatus
CC {ECO:0000269|PubMed:12006572}. Nucleus {ECO:0000250|UniProtKB:Q9Y2W7}.
CC Note=Also membrane-bound, associated with the plasma membrane. In the
CC presence of PSEN2 associated with the endoplasmic reticulum and Golgi.
CC The sumoylated form is present only in the nucleus.
CC {ECO:0000250|UniProtKB:Q9Y2W7}.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex, thalamus, dentate gyrus
CC and cerebellum (at protein level) (PubMed:16123112). Expressed in
CC brain. Colocalizes with KCND2 in excitatory neurons including cortical
CC and hippocampal CA1 pyramidal cells. {ECO:0000269|PubMed:15356203,
CC ECO:0000269|PubMed:16123112}.
CC -!- PTM: Palmitoylated. Palmitoylation enhances association with the plasma
CC membrane. {ECO:0000269|PubMed:12006572}.
CC -!- PTM: Proteolytically cleaved by caspase-3. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}.
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DR EMBL; AB043892; BAA96360.1; -; mRNA.
DR EMBL; AF297118; AAG15382.1; -; mRNA.
DR RefSeq; NP_115851.1; NM_032462.2.
DR AlphaFoldDB; Q9JM47; -.
DR BMRB; Q9JM47; -.
DR SMR; Q9JM47; -.
DR BioGRID; 249311; 1.
DR CORUM; Q9JM47; -.
DR STRING; 10116.ENSRNOP00000047927; -.
DR iPTMnet; Q9JM47; -.
DR PhosphoSitePlus; Q9JM47; -.
DR SwissPalm; Q9JM47; -.
DR PaxDb; Q9JM47; -.
DR PRIDE; Q9JM47; -.
DR ABCD; Q9JM47; 2 sequenced antibodies.
DR GeneID; 65199; -.
DR KEGG; rno:65199; -.
DR UCSC; RGD:70888; rat.
DR CTD; 30818; -.
DR RGD; 70888; Kcnip3.
DR VEuPathDB; HostDB:ENSRNOG00000014152; -.
DR eggNOG; KOG0044; Eukaryota.
DR HOGENOM; CLU_072366_2_2_1; -.
DR InParanoid; Q9JM47; -.
DR OMA; NIFHPET; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q9JM47; -.
DR Reactome; R-RNO-5576894; Phase 1 - inactivation of fast Na+ channels.
DR PRO; PR:Q9JM47; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000014152; Expressed in frontal cortex and 17 other tissues.
DR ExpressionAtlas; Q9JM47; baseline and differential.
DR Genevisible; Q9JM47; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032993; C:protein-DNA complex; IDA:RGD.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0005267; F:potassium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048266; P:behavioral response to pain; ISO:RGD.
DR GO; GO:0006886; P:intracellular protein transport; IMP:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0032026; P:response to magnesium ion; ISO:RGD.
DR GO; GO:0048265; P:response to pain; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
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; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW Apoptosis; Calcium; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW Golgi apparatus; Ion channel; Ion transport; Isopeptide bond; Lipoprotein;
KW Membrane; Metal-binding; Nucleus; Palmitate; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Transport;
KW Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..256
FT /note="Calsenilin"
FT /id="PRO_0000073817"
FT DOMAIN 67..123
FT /note="EF-hand 1; degenerate"
FT /evidence="ECO:0000305"
FT DOMAIN 126..161
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 162..197
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 210..245
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..256
FT /note="Interaction with KCND2"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 181
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXT8"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W7"
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 CROSSLNK 26
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W7"
FT CROSSLNK 90
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W7"
FT MUTAGEN 45..46
FT /note="CC->AA,SS: Greatly reduces plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:12006572"
FT CONFLICT 208
FT /note="E -> K (in Ref. 2; AAG15382)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 256 AA; 29471 MW; 6DF71E1584C1E9A0 CRC64;
MQRTKEAMKA SDGSLLGDPG RIPLSKREGI KWQRPRFTRQ ALMRCCLIKW ILSSAAPQGS
DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF KNECPTGLVD EDTFKLIYSQ
FFPQGDATTY AHFLFNAFDA DGNGAIHFED FVVGLSILLR GTVHEKLKWA FNLYDINKDG
YITKEEMLAI MKSIYDMMGR HTYPILREDA PLEHVERFFQ KMDRNQDGVV TIDEFLETCQ
KDENIMSSMQ LFENVI
