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Q9QXT8 (CSEN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calsenilin
Alternative name(s):
A-type potassium channel modulatory protein 3
DRE-antagonist modulator
Short name=DREAM
Kv channel-interacting protein 3
Short name=KChIP3
Gene names
Name:Kcnip3
Synonyms:Csen, Dream, Kchip3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length256 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-dependent transcriptional repressor that binds to the DRE element of genes including PDYN and FOS. Affinity for DNA is reduced upon binding to calcium and enhanced by binding to magnesium. Seems to be involved in nociception. Ref.8 Ref.11

Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Probably modulates channels density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and probably KCND3 trafficking to the cell surface By similarity. Ref.8 Ref.11

May play a role in the regulation of PSEN2 proteolytic processing and apoptosis. Together with PSEN2 involved in modulation of beta-amyloid formation By similarity. Ref.8 Ref.11

Subunit structure

Binds to DNA as a homomultimer. Dimerization is induced by binding to calcium. Interacts with the C-terminus of PSEN1 and PSEN2 and with PSEN2 CTF subunit. Associates with KCN1. Component of heteromultimeric potassium channels By similarity. Interacts with KCND2 and KCND3. Ref.7 Ref.9 Ref.13 Ref.14

Subcellular location

Cytoplasm. Cell membrane; Lipid-anchor. Endoplasmic reticulum. Golgi apparatus. Nucleus By similarity. Note: The sumoylated form is present only in the nucleus By similarity. In the presence of PSEN2, associated with the endoplasmic reticulum and Golgi.

Tissue specificity

Highly expressed in brain. Isoform 1 or isoform 4 (T+ forms) are expressed at equal levels with isoform 2 or isoform 3 (T- forms). Primarily detected in the layer V and deep layer VI of the cerebral cortex, the hippocampus, and the entire cerebellum. Expressed at low levels in testis. Also expressed in heart. Ref.1 Ref.6 Ref.10 Ref.12

Post-translational modification

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

Proteolytically cleaved by caspase-3 By similarity.

Miscellaneous

Mice deficient for Csen show a significant decrease of beta-amyloid protein 40 and beta-amyloid-protein 42, and display markedly reduced responses in models of acute thermal, mechanical, and visceral pain.

Sequence similarities

Belongs to the recoverin family.

Contains 4 EF-hand domains.

Ontologies

Keywords
   Biological processApoptosis
Ion transport
Potassium transport
Transcription
Transcription regulation
Transport
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Golgi apparatus
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandCalcium
Metal-binding
Potassium
   Molecular functionIon channel
Potassium channel
Repressor
Voltage-gated channel
   PTMIsopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

behavioral response to pain

Inferred from mutant phenotype Ref.11. Source: MGI

intracellular protein transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.8. Source: MGI

negative regulation of transcription, DNA-templated

Traceable author statement Ref.1. Source: MGI

potassium ion transport

Traceable author statement Ref.1. Source: MGI

regulation of neuron apoptotic process

Inferred from direct assay PubMed 17189291. Source: MGI

response to pain

Inferred from mutant phenotype Ref.8. Source: MGI

sensory perception of pain

Inferred from mutant phenotype Ref.8. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

axon terminus

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay PubMed 17189291. Source: MGI

dendrite

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 17189291. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

protein-DNA complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from direct assay Ref.8. Source: MGI

calcium ion binding

Inferred from electronic annotation. Source: InterPro

calcium-dependent protein binding

Inferred from physical interaction PubMed 17189291. Source: MGI

potassium channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

potassium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

protein C-terminus binding

Inferred from physical interaction PubMed 17189291. Source: MGI

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

voltage-gated ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QXT8-1)

Also known as: Calsenilin/KChIP3 T+;

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.
Isoform 2 (identifier: Q9QXT8-2)

Also known as: Calsenilin/KChIP3 T-;

The sequence of this isoform differs from the canonical sequence as follows:
     61-256: DSSDSELELS...NSMQLFENVI → AVTVNWSYPR...ASPRRRCWPS
Note: Lacks EF-hand domains.
Isoform 3 (identifier: Q9QXT8-3)

Also known as: DREAM T-;

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MQRTKEAVKA...LSSAAPQGSD → MRQLPAGPSS...DPVQCCPTRL
Isoform 4 (identifier: P0C092-1)

Also known as: DREAM T+;

The sequence of this isoform can be found in the external entry P0C092.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Lacks EF-hand domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 256256Calsenilin
PRO_0000073815

Regions

Domain67 – 12357EF-hand 1; degenerate
Domain126 – 16136EF-hand 2
Domain162 – 19736EF-hand 3
Domain210 – 24536EF-hand 4
Calcium binding175 – 186121 Ref.13 Ref.14
Calcium binding223 – 234122 Ref.13 Ref.14
Region243 – 25614Interaction with KCND2 By similarity

Amino acid modifications

Modified residue631Phosphoserine By similarity
Lipidation451S-palmitoyl cysteine By similarity
Lipidation461S-palmitoyl cysteine By similarity
Cross-link26Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity
Cross-link90Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Natural variations

Alternative sequence1 – 6161MQRTK…PQGSD → MRQLPAGPSSLACSGCKAGR LVTVPFSSRDAEDQGSREGI GWQPPGRSWAHTTEQEGKHQ VAKATVHPPGPDALLLNQVD PVQCCPTRL in isoform 3.
VSP_015041
Alternative sequence61 – 256196DSSDS…FENVI → AVTVNWSYPRCAISQRAWTS YKLRPSSPRRSCSPFTEASR MSVPQAWWMKTPSNSFIPSS SLREMPPPMHTSSSMPSMLM GTGPSTLRTLWLGSPSCFEG RSMRSSSGPSISMTLTRMVA SPRRRCWPS in isoform 2.
VSP_015042
Natural variant141N → S in strain: 129/Ola, BALB/c and FVB/NJ. Ref.1 Ref.3 Ref.4

Experimental info

Mutagenesis1861E → Q: Abolishes calcium-binding. Ref.13
Mutagenesis2341E → Q: Abolishes calcium-binding. Ref.13
Sequence conflict2461M → T in AAF14576. Ref.2

Secondary structure

.......................... 256
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Calsenilin/KChIP3 T+) [UniParc].

Last modified August 16, 2005. Version 2.
Checksum: 0F43D5F239D6378C

FASTA25629,463
        10         20         30         40         50         60 
MQRTKEAVKA SDGNLLGDPG RIPLSKRESI KWQRPRFTRQ ALMRCCLIKW ILSSAAPQGS 

        70         80         90        100        110        120 
DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF KNECPTGLVD EDTFKLIYSQ 

       130        140        150        160        170        180 
FFPQGDATTY AHFLFNAFDA DGNGAIHFED FVVGLSILLR GTVHEKLKWA FNLYDINKDG 

       190        200        210        220        230        240 
CITKEEMLAI MKSIYDMMGR HTYPILREDA PLEHVERFFQ KMDRNQDGVV TIDEFLETCQ 

       250 
KDENIMNSMQ LFENVI 

« Hide

Isoform 2 (Calsenilin/KChIP3 T-) [UniParc].

Checksum: 15D5915B2C70E185
Show »

FASTA18921,175
Isoform 3 (DREAM T-) [UniParc].

Checksum: 08592607D28ED530
Show »

FASTA28432,035
Isoform 4 (DREAM T+) [UniParc].

See P0C092.

References

« Hide 'large scale' references
[1]"Mouse DREAM/calsenilin/KChIP3: gene structure, coding potential and expression."
Spreafico F., Barski J.J., Farina C., Meyer M.
Mol. Cell. Neurosci. 17:1-16(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3), NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, VARIANT SER-14.
Strain: 129/Ola and C57BL/6.
[2]"Cloning and characterization of mouse calsenilin/DREAM."
Jo D.G., Kim M., Jung Y.K.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Allele of Mus musculus Dream/calsenilin gene."
Deng L., Reid R.E., Leavitt B., Hayden M.R.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-14.
Strain: FVB/NJ.
Tissue: Brain.
[4]Lee H.G., Choi J.K., Choi E.K., Wasco W., Buxbaum J.D., Beier D.R., Kim Y.S.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-14.
Strain: BALB/c.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Brain, Eye and Olfactory epithelium.
[6]"Modulation of A-type potassium channels by a family of calcium sensors."
An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G., Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J.
Nature 403:553-556(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription."
Liss B., Franz O., Sewing S., Bruns R., Neuhoff H., Roeper J.
EMBO J. 20:5715-5724(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCND3.
[8]"DREAM is a critical transcriptional repressor for pain modulation."
Cheng H.Y., Pitcher G.M., Laviolette S.R., Whishaw I.Q., Tong K.I., Kockeritz L.K., Wada T., Joza N.A., Crackower M., Goncalves J., Sarosi I., Woodgett J.R., Oliveira-dos-Santos A.J., Ikura M., van der Kooy D., Salter M.W., Penninger J.M.
Cell 108:31-43(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex."
Schrader L.A., Anderson A.E., Mayne A., Pfaffinger P.J., Sweatt J.D.
J. Neurosci. 22:10123-10133(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCND2.
[10]"Functional properties of a brain-specific NH2-terminally spliced modulator of Kv4 channels."
Boland L.M., Jiang M., Lee S.Y., Fahrenkrug S.C., Harnett M.T., O'Grady S.M.
Am. J. Physiol. 285:C161-C170(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[11]"Altered Abeta formation and long-term potentiation in a calsenilin knock-out."
Lilliehook C., Bozdagi O., Yao J., Gomez-Ramirez M., Zaidi N.F., Wasco W., Gandy S., Santucci A.C., Haroutunian V., Huntley G.W., Buxbaum J.D.
J. Neurosci. 23:9097-9106(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"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.
[13]"Mg2+ and Ca2+ differentially regulate DNA binding and dimerization of DREAM."
Osawa M., Dace A., Tong K.I., Valiveti A., Ikura M., Ames J.B.
J. Biol. Chem. 280:18008-18014(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, CALCIUM-BINDING, SUBUNIT, MUTAGENESIS OF GLU-186 AND GLU-234.
[14]"NMR structure of DREAM: implications for Ca(2+)-dependent DNA binding and protein dimerization."
Lusin J.D., Vanarotti M., Li C., Valiveti A., Ames J.B.
Biochemistry 47:2252-2264(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, SUBUNIT, DNA-BINDING, CALCIUM-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF287732 mRNA. Translation: AAK08175.1.
AF287733 mRNA. Translation: AAK08180.1.
AF287737 expand/collapse EMBL AC list , AF287734, AF287735, AF287736 Genomic DNA. Translation: AAK08176.1.
AF287737 expand/collapse EMBL AC list , AF287734, AF287735, AF287736 Genomic DNA. Translation: AAK08177.1.
AF287737 expand/collapse EMBL AC list , AF287734, AF287735, AF287736 Genomic DNA. Translation: AAK08179.1.
AF184624 mRNA. Translation: AAF14576.1.
AF274050 mRNA. Translation: AAF74784.1.
AF300870 mRNA. Translation: AAG17450.1.
BC026980 mRNA. Translation: AAH26980.1.
BC047139 mRNA. Translation: AAH47139.1.
BC057329 mRNA. Translation: AAH57329.1.
RefSeqNP_001104801.1. NM_001111331.1.
NP_062763.2. NM_019789.3.
UniGeneMm.315292.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JULNMR-A1-256[»]
DisProtDP00291.
ProteinModelPortalQ9QXT8.
SMRQ9QXT8. Positions 76-256.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid208000. 1 interaction.
MINTMINT-193520.
STRING10090.ENSMUSP00000028850.

PTM databases

PhosphoSiteQ9QXT8.

Proteomic databases

PRIDEQ9QXT8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000103215; ENSMUSP00000099504; ENSMUSG00000079056. [Q9QXT8-1]
GeneID56461.
KEGGmmu:56461.
UCSCuc008mfm.1. mouse. [Q9QXT8-1]

Organism-specific databases

CTD30818.
MGIMGI:1929258. Kcnip3.

Phylogenomic databases

GeneTreeENSGT00560000076973.
HOVERGENHBG108179.
TreeFamTF318560.

Gene expression databases

ArrayExpressQ9QXT8.
BgeeQ9QXT8.
CleanExMM_KCNIP3.
GenevestigatorQ9QXT8.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin_like.
[Graphical view]
PfamPF13499. EF-hand_7. 1 hit.
[Graphical view]
PRINTSPR00450. RECOVERIN.
SMARTSM00054. EFh. 3 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9QXT8.
NextBio312710.
PROQ9QXT8.
SOURCESearch...

Entry information

Entry nameCSEN_MOUSE
AccessionPrimary (citable) accession number: Q9QXT8
Secondary accession number(s): Q924L0 expand/collapse secondary AC list , Q99PH9, Q99PI0, Q99PI2, Q99PI3, Q9JHZ5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 16, 2005
Last modified: April 16, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot