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Protein

Calsenilin

Gene

Kcnip3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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, such as KCND2/Kv4.2 and KCND3/Kv4.3. Modulates channel expression at the cell membrane, gating characteristics, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner.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).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi175 – 1861Add BLAST12
Calcium bindingi223 – 2342Add BLAST12

GO - Molecular functioni

  • calcium-dependent protein binding Source: MGI
  • calcium ion binding Source: InterPro
  • DNA binding Source: MGI
  • potassium channel activity Source: UniProtKB-KW
  • potassium channel regulator activity Source: UniProtKB
  • protein C-terminus binding Source: MGI
  • voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • behavioral response to pain Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • potassium ion transport Source: MGI
  • protein localization to plasma membrane Source: UniProtKB
  • regulation of neuron apoptotic process Source: MGI
  • regulation of potassium ion transmembrane transport Source: UniProtKB
  • response to pain Source: MGI
  • sensory perception of pain Source: MGI
  • 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

Enzyme and pathway databases

ReactomeiR-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1929258. Kcnip3.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Cell membrane By similarity; Lipid-anchor
  • Endoplasmic reticulum By similarity
  • Golgi apparatus By similarity
  • Nucleus By similarity

  • Note: The sumoylated form is present only in the nucleus. In the presence of PSEN2, associated with the endoplasmic reticulum and Golgi.By similarity

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi186E → Q: Abolishes calcium-binding. 1 Publication1
Mutagenesisi234E → Q: Abolishes calcium-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000738151 – 256CalsenilinAdd BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki26Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Lipidationi45S-palmitoyl cysteineBy similarity1
Lipidationi46S-palmitoyl cysteineBy similarity1
Modified residuei60PhosphoserineCombined sources1
Modified residuei63PhosphoserineBy similarity1
Cross-linki90Glycyl 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).By similarity
Proteolytically cleaved by caspase-3.By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9QXT8.
PRIDEiQ9QXT8.

PTM databases

iPTMnetiQ9QXT8.
PhosphoSitePlusiQ9QXT8.

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

BgeeiENSMUSG00000079056.
CleanExiMM_KCNIP3.
ExpressionAtlasiQ9QXT8. baseline and differential.
GenevisibleiQ9QXT8. MM.

Interactioni

Subunit structurei

Binds to DNA as a homomultimer. Dimerization is induced by binding to calcium (PubMed:18201103). Interacts with the C-terminus of PSEN1 and PSEN2 and with PSEN2 CTF subunit. Associates with KCN1. Component of heteromultimeric potassium channels (PubMed:19713751). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). Interacts with KCND2 and KCND3 (PubMed:11598014, PubMed:12451113, PubMed:20943905).Curated5 Publications

GO - Molecular functioni

  • calcium-dependent protein binding Source: MGI
  • protein C-terminus binding Source: MGI

Protein-protein interaction databases

BioGridi208000. 1 interactor.
IntActiQ9QXT8. 1 interactor.
MINTiMINT-193520.
STRINGi10090.ENSMUSP00000099504.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi78 – 85Combined sources8
Helixi90 – 103Combined sources14
Beta strandi107 – 110Combined sources4
Helixi111 – 121Combined sources11
Helixi128 – 137Combined sources10
Beta strandi144 – 146Combined sources3
Helixi149 – 159Combined sources11
Helixi163 – 173Combined sources11
Beta strandi177 – 180Combined sources4
Helixi184 – 197Combined sources14
Helixi211 – 221Combined sources11
Helixi232 – 241Combined sources10
Helixi245 – 255Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JULNMR-A1-256[»]
DisProtiDP00291.
ProteinModelPortaliQ9QXT8.
SMRiQ9QXT8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QXT8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini67 – 123EF-hand 1; degeneratePROSITE-ProRule annotationAdd BLAST57
Domaini126 – 161EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini162 – 197EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini210 – 245EF-hand 4PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni243 – 256Interaction with KCND2By similarityAdd BLAST14

Sequence similaritiesi

Belongs to the recoverin family.Curated
Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOVERGENiHBG108179.
InParanoidiQ9QXT8.
TreeFamiTF318560.

Family and domain databases

CDDicd00051. EFh. 2 hits.
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.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
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. AlignAdd to basket

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

        10         20         30         40         50
MQRTKEAVKA SDGNLLGDPG RIPLSKRESI KWQRPRFTRQ ALMRCCLIKW
60 70 80 90 100
ILSSAAPQGS DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF
110 120 130 140 150
KNECPTGLVD EDTFKLIYSQ FFPQGDATTY AHFLFNAFDA DGNGAIHFED
160 170 180 190 200
FVVGLSILLR GTVHEKLKWA FNLYDINKDG CITKEEMLAI MKSIYDMMGR
210 220 230 240 250
HTYPILREDA PLEHVERFFQ KMDRNQDGVV TIDEFLETCQ KDENIMNSMQ

LFENVI
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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246M → T in AAF14576 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti14N → S in strain: 129/Ola, BALB/c and FVB/NJ. 3 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0150411 – 61MQRTK…PQGSD → MRQLPAGPSSLACSGCKAGR LVTVPFSSRDAEDQGSREGI GWQPPGRSWAHTTEQEGKHQ VAKATVHPPGPDALLLNQVD PVQCCPTRL in isoform 3. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_01504261 – 256DSSDS…FENVI → AVTVNWSYPRCAISQRAWTS YKLRPSSPRRSCSPFTEASR MSVPQAWWMKTPSNSFIPSS SLREMPPPMHTSSSMPSMLM GTGPSTLRTLWLGSPSCFEG RSMRSSSGPSISMTLTRMVA SPRRRCWPS in isoform 2. 1 PublicationAdd BLAST196

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.2. mouse. [Q9QXT8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JULNMR-A1-256[»]
DisProtiDP00291.
ProteinModelPortaliQ9QXT8.
SMRiQ9QXT8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208000. 1 interactor.
IntActiQ9QXT8. 1 interactor.
MINTiMINT-193520.
STRINGi10090.ENSMUSP00000099504.

PTM databases

iPTMnetiQ9QXT8.
PhosphoSitePlusiQ9QXT8.

Proteomic databases

PaxDbiQ9QXT8.
PRIDEiQ9QXT8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000103215; ENSMUSP00000099504; ENSMUSG00000079056. [Q9QXT8-1]
GeneIDi56461.
KEGGimmu:56461.
UCSCiuc008mfm.2. mouse. [Q9QXT8-1]

Organism-specific databases

CTDi30818.
MGIiMGI:1929258. Kcnip3.

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOVERGENiHBG108179.
InParanoidiQ9QXT8.
TreeFamiTF318560.

Enzyme and pathway databases

ReactomeiR-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

Miscellaneous databases

EvolutionaryTraceiQ9QXT8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000079056.
CleanExiMM_KCNIP3.
ExpressionAtlasiQ9QXT8. baseline and differential.
GenevisibleiQ9QXT8. MM.

Family and domain databases

CDDicd00051. EFh. 2 hits.
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.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 139 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.