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Q9QXT8

- CSEN_MOUSE

UniProt

Q9QXT8 - CSEN_MOUSE

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Protein
Calsenilin
Gene
Kcnip3, Csen, Dream, Kchip3
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications
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.2 Publications
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.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi175 – 1861212 Publications
Add
BLAST
Calcium bindingi223 – 2341222 Publications
Add
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. calcium ion binding Source: InterPro
  3. calcium-dependent protein binding Source: MGI
  4. potassium channel activity Source: UniProtKB-KW
  5. potassium channel regulator activity Source: Ensembl
  6. protein C-terminus binding Source: MGI
  7. sequence-specific DNA binding Source: Ensembl
  8. voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. behavioral response to pain Source: MGI
  3. intracellular protein transport Source: Ensembl
  4. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  5. negative regulation of transcription, DNA-templated Source: MGI
  6. potassium ion transport Source: MGI
  7. regulation of neuron apoptotic process Source: MGI
  8. response to pain Source: MGI
  9. sensory perception of pain Source: MGI
  10. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Repressor, Voltage-gated channel

Keywords - Biological processi

Apoptosis, Ion transport, Potassium transport, Transcription, Transcription regulation, Transport

Keywords - Ligandi

Calcium, Metal-binding, Potassium

Names & Taxonomyi

Protein namesi
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 namesi
Name:Kcnip3
Synonyms:Csen, Dream, Kchip3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:1929258. Kcnip3.

Subcellular locationi

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.

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB-SubCell
  2. axon terminus Source: Ensembl
  3. cytosol Source: MGI
  4. dendrite Source: Ensembl
  5. endoplasmic reticulum Source: UniProtKB-SubCell
  6. nucleus Source: MGI
  7. plasma membrane Source: UniProtKB-SubCell
  8. protein-DNA complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi186 – 1861E → Q: Abolishes calcium-binding. 1 Publication
Mutagenesisi234 – 2341E → Q: Abolishes calcium-binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 256256Calsenilin
PRO_0000073815Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki26 – 26Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity
Lipidationi45 – 451S-palmitoyl cysteine By similarity
Lipidationi46 – 461S-palmitoyl cysteine By similarity
Modified residuei63 – 631Phosphoserine By similarity
Cross-linki90 – 90Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Post-translational modificationi

Palmitoylated. Palmitoylation enhances association with the plasma membrane By similarity.
Proteolytically cleaved by caspase-3 By similarity.

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ9QXT8.

PTM databases

PhosphoSiteiQ9QXT8.

Expressioni

Tissue specificityi

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.4 Publications

Gene expression databases

ArrayExpressiQ9QXT8.
BgeeiQ9QXT8.
CleanExiMM_KCNIP3.
GenevestigatoriQ9QXT8.

Interactioni

Subunit structurei

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 KCND3.4 Publications

Protein-protein interaction databases

BioGridi208000. 1 interaction.
MINTiMINT-193520.
STRINGi10090.ENSMUSP00000028850.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi78 – 858
Helixi90 – 10314
Beta strandi107 – 1104
Helixi111 – 12111
Helixi128 – 13710
Beta strandi144 – 1463
Helixi149 – 15911
Helixi163 – 17311
Beta strandi177 – 1804
Helixi184 – 19714
Helixi211 – 22111
Helixi232 – 24110
Helixi245 – 25511

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JULNMR-A1-256[»]
DisProtiDP00291.
ProteinModelPortaliQ9QXT8.
SMRiQ9QXT8. Positions 76-256.

Miscellaneous databases

EvolutionaryTraceiQ9QXT8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini67 – 12357EF-hand 1; degenerate
Add
BLAST
Domaini126 – 16136EF-hand 2
Add
BLAST
Domaini162 – 19736EF-hand 3
Add
BLAST
Domaini210 – 24536EF-hand 4
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni243 – 25614Interaction with KCND2 By similarity
Add
BLAST

Sequence similaritiesi

Belongs to the recoverin family.
Contains 4 EF-hand domains.

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00560000076973.
HOVERGENiHBG108179.
TreeFamiTF318560.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028846. Recoverin.
[Graphical view]
PANTHERiPTHR23055. PTHR23055. 1 hit.
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9QXT8-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MQRTKEAVKA SDGNLLGDPG RIPLSKRESI KWQRPRFTRQ ALMRCCLIKW    50
ILSSAAPQGS DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF 100
KNECPTGLVD EDTFKLIYSQ FFPQGDATTY AHFLFNAFDA DGNGAIHFED 150
FVVGLSILLR GTVHEKLKWA FNLYDINKDG CITKEEMLAI MKSIYDMMGR 200
HTYPILREDA PLEHVERFFQ KMDRNQDGVV TIDEFLETCQ KDENIMNSMQ 250
LFENVI 256
Length:256
Mass (Da):29,463
Last modified:August 16, 2005 - v2
Checksum:i0F43D5F239D6378C
GO
Isoform 2 (identifier: Q9QXT8-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:189
Mass (Da):21,175
Checksum:i15D5915B2C70E185
GO
Isoform 3 (identifier: Q9QXT8-3) [UniParc]FASTAAdd to Basket

Also known as: DREAM T-

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MQRTKEAVKA...LSSAAPQGSD → MRQLPAGPSS...DPVQCCPTRL

Show »
Length:284
Mass (Da):32,035
Checksum:i08592607D28ED530
GO
Isoform 4 (identifier: P0C092-1) [UniParc]FASTAAdd to Basket

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.

Length:89
Mass (Da):9,471
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti14 – 141N → S in strain: 129/Ola, BALB/c and FVB/NJ. 3 Publications

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6161MQRTK…PQGSD → MRQLPAGPSSLACSGCKAGR LVTVPFSSRDAEDQGSREGI GWQPPGRSWAHTTEQEGKHQ VAKATVHPPGPDALLLNQVD PVQCCPTRL in isoform 3.
VSP_015041Add
BLAST
Alternative sequencei61 – 256196DSSDS…FENVI → AVTVNWSYPRCAISQRAWTS YKLRPSSPRRSCSPFTEASR MSVPQAWWMKTPSNSFIPSS SLREMPPPMHTSSSMPSMLM GTGPSTLRTLWLGSPSCFEG RSMRSSSGPSISMTLTRMVA SPRRRCWPS in isoform 2.
VSP_015042Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti246 – 2461M → T in AAF14576. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS16703.1. [Q9QXT8-1]
CCDS71139.1. [Q9QXT8-3]
RefSeqiNP_001104801.1. NM_001111331.1.
NP_001277934.1. NM_001291005.1.
NP_062763.2. NM_019789.4. [Q9QXT8-1]
UniGeneiMm.315292.

Genome annotation databases

EnsembliENSMUST00000103215; ENSMUSP00000099504; ENSMUSG00000079056. [Q9QXT8-1]
GeneIDi56461.
KEGGimmu:56461.
UCSCiuc008mfm.1. mouse. [Q9QXT8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS16703.1. [Q9QXT8-1 ]
CCDS71139.1. [Q9QXT8-3 ]
RefSeqi NP_001104801.1. NM_001111331.1.
NP_001277934.1. NM_001291005.1.
NP_062763.2. NM_019789.4. [Q9QXT8-1 ]
UniGenei Mm.315292.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2JUL NMR - A 1-256 [» ]
DisProti DP00291.
ProteinModelPortali Q9QXT8.
SMRi Q9QXT8. Positions 76-256.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 208000. 1 interaction.
MINTi MINT-193520.
STRINGi 10090.ENSMUSP00000028850.

PTM databases

PhosphoSitei Q9QXT8.

Proteomic databases

PRIDEi Q9QXT8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000103215 ; ENSMUSP00000099504 ; ENSMUSG00000079056 . [Q9QXT8-1 ]
GeneIDi 56461.
KEGGi mmu:56461.
UCSCi uc008mfm.1. mouse. [Q9QXT8-1 ]

Organism-specific databases

CTDi 30818.
MGIi MGI:1929258. Kcnip3.

Phylogenomic databases

GeneTreei ENSGT00560000076973.
HOVERGENi HBG108179.
TreeFami TF318560.

Miscellaneous databases

EvolutionaryTracei Q9QXT8.
NextBioi 312710.
PROi Q9QXT8.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9QXT8.
Bgeei Q9QXT8.
CleanExi MM_KCNIP3.
Genevestigatori Q9QXT8.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
InterProi IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028846. Recoverin.
[Graphical view ]
PANTHERi PTHR23055. PTHR23055. 1 hit.
Pfami PF13499. EF-hand_7. 1 hit.
[Graphical view ]
SMARTi SM00054. EFh. 3 hits.
[Graphical view ]
PROSITEi PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiCSEN_MOUSE
AccessioniPrimary (citable) accession number: Q9QXT8
Secondary accession number(s): Q924L0
, Q99PH9, Q99PI0, Q99PI2, Q99PI3, Q9JHZ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 16, 2005
Last modified: September 3, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi