Q9QXT8 (CSEN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	256 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Ion transport Potassium transport Transcription Transcription regulation Transport
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Golgi apparatus Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding Potassium
Molecular function	Ion channel Potassium channel Repressor Voltage-gated channel
PTM	Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW behavior Inferred from mutant phenotype Ref.11. Source: MGI intracellular protein transport Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.8. 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay PubMed 17189291. Source: MGI 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
Molecular_function	DNA binding Inferred from direct assay Ref.8. Source: MGI calcium ion binding Inferred from electronic annotation. Source: InterPro potassium channel activity Inferred from electronic annotation. Source: UniProtKB-KW potassium channel regulator activity Inferred from electronic annotation. Source: Compara 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 256

256

Calsenilin

PRO_0000073815

Regions

Domain

67 – 123

57

EF-hand 1; degenerate

Domain

126 – 161

36

EF-hand 2

Domain

162 – 197

36

EF-hand 3

Domain

210 – 245

36

EF-hand 4

Calcium binding

175 – 186

12

1 Ref.13 Ref.14

Calcium binding

223 – 234

12

2 Ref.13 Ref.14

Region

243 – 256

14

Interaction with KCND2 By similarity

Amino acid modifications

Modified residue

63

1

Phosphoserine By similarity

Lipidation

45

1

S-palmitoyl cysteine By similarity

Lipidation

46

1

S-palmitoyl cysteine By similarity

Cross-link

26

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Cross-link

90

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Natural variations

Alternative sequence

1 – 61

61

MQRTK…PQGSD → MRQLPAGPSSLACSGCKAGR LVTVPFSSRDAEDQGSREGI GWQPPGRSWAHTTEQEGKHQ VAKATVHPPGPDALLLNQVD PVQCCPTRL in isoform 3.

VSP_015041

Alternative sequence

61 – 256

196

DSSDS…FENVI → AVTVNWSYPRCAISQRAWTS YKLRPSSPRRSCSPFTEASR MSVPQAWWMKTPSNSFIPSS SLREMPPPMHTSSSMPSMLM GTGPSTLRTLWLGSPSCFEG RSMRSSSGPSISMTLTRMVA SPRRRCWPS in isoform 2.

VSP_015042

Natural variant

14

1

N → S in strain: 129/Ola, BALB/c and FVB/NJ. Ref.1 Ref.3 Ref.4

Experimental info

Mutagenesis

186

1

E → Q: Abolishes calcium-binding. Ref.13

Mutagenesis

234

1

E → Q: Abolishes calcium-binding. Ref.13

Sequence conflict

246

1

M → T in AAF14576. Ref.2

Secondary structure

1

.

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256

Helix Strand Turn

Details...

Helix

78 – 85

8

Helix

90 – 103

14

Beta strand

107 – 110

4

Helix

111 – 121

11

Helix

128 – 137

10

Beta strand

144 – 146

3

Helix

149 – 159

11

Helix

163 – 173

11

Beta strand

177 – 180

4

Helix

184 – 197

14

Helix

211 – 221

11

Helix

232 – 241

10

Helix

245 – 255

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Calsenilin/KChIP3 T+) [UniParc]. Last modified August 16, 2005. Version 2. Checksum: 0F43D5F239D6378C	FASTA	256	29,463
	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
	Isoform 2 (Calsenilin/KChIP3 T-) [UniParc]. Checksum: 15D5915B2C70E185	FASTA	189	21,175
	10 20 30 40 50 60 MQRTKEAVKA SDGNLLGDPG RIPLSKRESI KWQRPRFTRQ ALMRCCLIKW ILSSAAPQGS 70 80 90 100 110 120 AVTVNWSYPR CAISQRAWTS YKLRPSSPRR SCSPFTEASR MSVPQAWWMK TPSNSFIPSS 130 140 150 160 170 180 SLREMPPPMH TSSSMPSMLM GTGPSTLRTL WLGSPSCFEG RSMRSSSGPS ISMTLTRMVA SPRRRCWPS
	Isoform 3 (DREAM T-) [UniParc]. Checksum: 08592607D28ED530	FASTA	284	32,035
	10 20 30 40 50 60 MRQLPAGPSS LACSGCKAGR LVTVPFSSRD AEDQGSREGI GWQPPGRSWA HTTEQEGKHQ 70 80 90 100 110 120 VAKATVHPPG PDALLLNQVD PVQCCPTRLS SDSELELSTV RHQPEGLDQL QAQTKFTKKE 130 140 150 160 170 180 LQSLYRGFKN ECPTGLVDED TFKLIYSQFF PQGDATTYAH FLFNAFDADG NGAIHFEDFV 190 200 210 220 230 240 VGLSILLRGT VHEKLKWAFN LYDINKDGCI TKEEMLAIMK SIYDMMGRHT YPILREDAPL 250 260 270 280 EHVERFFQKM DRNQDGVVTI DEFLETCQKD ENIMNSMQLF ENVI
	Isoform 4 (DREAM T+) [UniParc]. See P0C092.		–	–

References

	« Hide 'large scale' referencesShow '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 , AF287734, AF287735, AF287736 Genomic DNA. Translation: AAK08176.1.
AF287737 , AF287734, AF287735, AF287736 Genomic DNA. Translation: AAK08177.1.
AF287737 , 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.

IPI

IPI00135534.
IPI00474630.
IPI00475040.

RefSeq

NP_001104801.1. NM_001111331.1.
NP_062763.2. NM_019789.3.

UniGene

Mm.315292.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JUL	NMR	-	A	1-256	[»]

DisProt

DP00291.

ProteinModelPortal

Q9QXT8.

SMR

Q9QXT8. Positions 76-256.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-193520.

STRING

10090.ENSMUSP00000028850.

PTM databases

PhosphoSite

Q9QXT8.

Proteomic databases

PRIDE

Q9QXT8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000103215; ENSMUSP00000099504; ENSMUSG00000079056.

GeneID

56461.

KEGG

mmu:56461.

UCSC

uc008mfm.1. mouse.

Organism-specific databases

CTD

30818.

MGI

MGI:1929258. Kcnip3.

Phylogenomic databases

GeneTree

ENSGT00560000076973.

HOVERGEN

HBG108179.

Gene expression databases

ArrayExpress

Q9QXT8.

Bgee

Q9QXT8.

CleanEx

MM_KCNIP3.

Genevestigator

Q9QXT8.

GermOnline

ENSMUSG00000027376. Mus musculus.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin.
[Graphical view]

Pfam

PF13499. EF_hand_5. 1 hit.
[Graphical view]

PRINTS

PR00450. RECOVERIN.

SMART

SM00054. EFh. 3 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9QXT8.

NextBio

312710.

SOURCE

Search...

Entry information

Entry name

CSEN_MOUSE

Accession

Primary (citable) accession number: Q9QXT8
Secondary accession number(s): Q924L0 , Q99PH9, Q99PI0, Q99PI2, Q99PI3, Q9JHZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	August 16, 2005
Last modified:	May 29, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program