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Protein

Calsenilin

Gene

KCNIP3

Organism
Homo sapiens (Human)
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 (By similarity).By similarity
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.5 Publications
May play a role in the regulation of PSEN2 proteolytic processing and apoptosis. Together with PSEN2 involved in modulation of beta-amyloid formation.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi175 – 1861PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi223 – 2342PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • calcium ion binding Source: ProtInc
  • DNA binding Source: ProtInc
  • potassium channel activity Source: UniProtKB-KW
  • potassium channel regulator activity Source: UniProtKB
  • sequence-specific DNA binding Source: Ensembl
  • transcription corepressor activity Source: ProtInc
  • voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

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

BioCyciZFISH:ENSG00000115041-MONOMER.
ReactomeiR-HSA-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:15523. KCNIP3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61D → A: Abolishes cleavage by caspase-3. 1 Publication1
Mutagenesisi64D → A: Abolishes cleavage by caspase-3. 1 Publication1

Organism-specific databases

DisGeNETi30818.
OpenTargetsiENSG00000115041.
PharmGKBiPA26934.

Polymorphism and mutation databases

BioMutaiKCNIP3.
DMDMi13431428.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000738141 – 256CalsenilinAdd BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineBy similarity1
Cross-linki26Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Lipidationi45S-palmitoyl cysteineBy similarity1
Lipidationi46S-palmitoyl cysteineBy similarity1
Modified residuei60PhosphoserineBy similarity1
Modified residuei63Phosphoserine; by CK11 Publication1
Cross-linki90Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication

Post-translational modificationi

Palmitoylated. Palmitoylation enhances association with the plasma membrane (By similarity).By similarity
Proteolytically cleaved by caspase-3.1 Publication
Phosphorylation at Ser-63 inhibits cleavage by CASP3.2 Publications

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9Y2W7.
PeptideAtlasiQ9Y2W7.
PRIDEiQ9Y2W7.

PTM databases

iPTMnetiQ9Y2W7.
PhosphoSitePlusiQ9Y2W7.

Miscellaneous databases

PMAP-CutDBQ3YAC3.

Expressioni

Tissue specificityi

Highly expressed in brain. Widely expressed at lower levels. Expression levels are elevated in brain cortex regions affected by Alzheimer disease.1 Publication

Gene expression databases

BgeeiENSG00000115041.
CleanExiHS_KCNIP3.
ExpressionAtlasiQ9Y2W7. baseline and differential.
GenevisibleiQ9Y2W7. HS.

Organism-specific databases

HPAiCAB006907.

Interactioni

Subunit structurei

Binds to DNA as a homomultimer. Dimerization is induced by binding to calcium (PubMed:17962406). Interacts with the C-terminus of PSEN1 and PSEN2 and with PSEN2 CTF subunit. Associates with KCN1. Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with KCND2 and KCND3.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD177Q8N6Q36EBI-751501,EBI-747170
IGF1RP080695EBI-751501,EBI-475981
IL6STQ17RA03EBI-751501,EBI-10238517
MAVSQ7Z4343EBI-751501,EBI-995373

Protein-protein interaction databases

BioGridi119042. 21 interactors.
IntActiQ9Y2W7. 7 interactors.
MINTiMINT-1453732.
STRINGi9606.ENSP00000295225.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi164 – 174Combined sources11
Beta strandi179 – 182Combined sources4
Helixi184 – 193Combined sources10
Beta strandi211 – 213Combined sources3
Helixi214 – 222Combined sources9
Beta strandi227 – 231Combined sources5
Helixi232 – 239Combined sources8
Helixi243 – 254Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E6WNMR-A161-256[»]
ProteinModelPortaliQ9Y2W7.
SMRiQ9Y2W7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y2W7.

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.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiQ9Y2W7.
OMAiFGILEPM.
PhylomeDBiQ9Y2W7.
TreeFamiTF318560.

Family and domain databases

CDDicd00051. EFh. 2 hits.
Gene3Di1.10.238.10. 3 hits.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y2W7-1) [UniParc]FASTAAdd to basket
Also known as: KChIP3.1

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
MQPAKEVTKA SDGSLLGDLG HTPLSKKEGI KWQRPRLSRQ ALMRCCLVKW
60 70 80 90 100
ILSSTAPQGS DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF
110 120 130 140 150
KNECPTGLVD EDTFKLIYAQ FFPQGDATTY AHFLFNAFDA DGNGAIHFED
160 170 180 190 200
FVVGLSILLR GTVHEKLKWA FNLYDINKDG YITKEEMLAI MKSIYDMMGR
210 220 230 240 250
HTYPILREDA PAEHVERFFE KMDRNQDGVV TIEEFLEACQ KDENIMSSMQ

LFENVI
Length:256
Mass (Da):29,231
Last modified:November 1, 1999 - v1
Checksum:i635C3EDF8B91E1C5
GO
Isoform 2 (identifier: Q9Y2W7-2) [UniParc]FASTAAdd to basket
Also known as: KChIP3.2, KChIP4.2

The sequence of this isoform differs from the canonical sequence as follows:
     103-124: Missing.

Note: No experimental confirmation available.
Show »
Length:234
Mass (Da):26,687
Checksum:i4AC9058CBBD08169
GO
Isoform 3 (identifier: Q9Y2W7-3) [UniParc]FASTAAdd to basket
Also known as: KChip3.x

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.
     27-60: KEGIKWQRPRLSRQALMRCCLVKWILSSTAPQGS → MGIQGMELCAMAVVVLLFIAVLKQFGILEPISME

Show »
Length:230
Mass (Da):26,335
Checksum:iE6CEC7D4A37E5705
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti182I → V in CAB56836 (PubMed:10078534).Curated1
Sequence conflicti182I → V in CAB56835 (PubMed:10078534).Curated1
Sequence conflicti207R → Q in CAB56836 (PubMed:10078534).Curated1
Sequence conflicti207R → Q in CAB56835 (PubMed:10078534).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048663119A → V.Corresponds to variant rs35658670dbSNPEnsembl.1
Natural variantiVAR_035463170A → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_035464179D → Y in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0409821 – 26Missing in isoform 3. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_04098327 – 60KEGIK…APQGS → MGIQGMELCAMAVVVLLFIA VLKQFGILEPISME in isoform 3. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_015040103 – 124Missing in isoform 2. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF120102 mRNA. Translation: AAD20350.1.
AJ131730 mRNA. Translation: CAB56836.1.
AJ131730 mRNA. Translation: CAB56835.1.
AF199599 mRNA. Translation: AAF33684.1.
DQ148485 mRNA. Translation: AAZ77802.1.
DQ148486 mRNA. Translation: AAZ77803.1.
AF367022 mRNA. Translation: AAK53711.1.
BT020075 mRNA. Translation: AAV38878.1.
AK315437 mRNA. Translation: BAG37825.1.
AC009238 Genomic DNA. Translation: AAY14752.1.
CH471219 Genomic DNA. Translation: EAX10724.1.
BC012850 mRNA. Translation: AAH12850.1.
CCDSiCCDS2013.1. [Q9Y2W7-1]
CCDS33245.1. [Q9Y2W7-3]
RefSeqiNP_001030086.1. NM_001034914.1. [Q9Y2W7-3]
NP_038462.1. NM_013434.4. [Q9Y2W7-1]
UniGeneiHs.437376.

Genome annotation databases

EnsembliENST00000295225; ENSP00000295225; ENSG00000115041. [Q9Y2W7-1]
ENST00000468529; ENSP00000417499; ENSG00000115041. [Q9Y2W7-3]
GeneIDi30818.
KEGGihsa:30818.
UCSCiuc002sup.4. human. [Q9Y2W7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF120102 mRNA. Translation: AAD20350.1.
AJ131730 mRNA. Translation: CAB56836.1.
AJ131730 mRNA. Translation: CAB56835.1.
AF199599 mRNA. Translation: AAF33684.1.
DQ148485 mRNA. Translation: AAZ77802.1.
DQ148486 mRNA. Translation: AAZ77803.1.
AF367022 mRNA. Translation: AAK53711.1.
BT020075 mRNA. Translation: AAV38878.1.
AK315437 mRNA. Translation: BAG37825.1.
AC009238 Genomic DNA. Translation: AAY14752.1.
CH471219 Genomic DNA. Translation: EAX10724.1.
BC012850 mRNA. Translation: AAH12850.1.
CCDSiCCDS2013.1. [Q9Y2W7-1]
CCDS33245.1. [Q9Y2W7-3]
RefSeqiNP_001030086.1. NM_001034914.1. [Q9Y2W7-3]
NP_038462.1. NM_013434.4. [Q9Y2W7-1]
UniGeneiHs.437376.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E6WNMR-A161-256[»]
ProteinModelPortaliQ9Y2W7.
SMRiQ9Y2W7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119042. 21 interactors.
IntActiQ9Y2W7. 7 interactors.
MINTiMINT-1453732.
STRINGi9606.ENSP00000295225.

PTM databases

iPTMnetiQ9Y2W7.
PhosphoSitePlusiQ9Y2W7.

Polymorphism and mutation databases

BioMutaiKCNIP3.
DMDMi13431428.

Proteomic databases

PaxDbiQ9Y2W7.
PeptideAtlasiQ9Y2W7.
PRIDEiQ9Y2W7.

Protocols and materials databases

DNASUi30818.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295225; ENSP00000295225; ENSG00000115041. [Q9Y2W7-1]
ENST00000468529; ENSP00000417499; ENSG00000115041. [Q9Y2W7-3]
GeneIDi30818.
KEGGihsa:30818.
UCSCiuc002sup.4. human. [Q9Y2W7-1]

Organism-specific databases

CTDi30818.
DisGeNETi30818.
GeneCardsiKCNIP3.
HGNCiHGNC:15523. KCNIP3.
HPAiCAB006907.
MIMi604662. gene.
neXtProtiNX_Q9Y2W7.
OpenTargetsiENSG00000115041.
PharmGKBiPA26934.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiQ9Y2W7.
OMAiFGILEPM.
PhylomeDBiQ9Y2W7.
TreeFamiTF318560.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115041-MONOMER.
ReactomeiR-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Miscellaneous databases

ChiTaRSiKCNIP3. human.
EvolutionaryTraceiQ9Y2W7.
GeneWikiiCalsenilin.
GenomeRNAii30818.
PMAP-CutDBQ3YAC3.
PROiQ9Y2W7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115041.
CleanExiHS_KCNIP3.
ExpressionAtlasiQ9Y2W7. baseline and differential.
GenevisibleiQ9Y2W7. HS.

Family and domain databases

CDDicd00051. EFh. 2 hits.
Gene3Di1.10.238.10. 3 hits.
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_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2W7
Secondary accession number(s): H7BY46
, Q3YAC3, Q3YAC4, Q53TJ5, Q96T40, Q9UJ84, Q9UJ85
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1999
Last modified: November 30, 2016
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.