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calsenilin; Kv channel-interacting protein 3; KChIP3; A-type K+ channel modulatory protein 3; DRE-antagonist modulator; DREAM (KCNIP3, CSEN, DREAM, KCHIP3)

Function: - Ca+2-dependent transcriptional repressor that binds to the DRE element of genes including PDYN & FOS - affinity for DNA is reduced upon binding to Ca+2 & enhanced by binding to Mg+2 - seems to be involved in nociception (putative) - regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type K+ channels - probably modulates channels density, inactivation kinetics & rate of recovery from inactivation in a Ca+2-dependent & isoform-specific manner in vitro, modulates KCND2/Kv4.2 & KCND3/Kv4.3 currents - involved in KCND2 & probably KCND3 trafficking to the cell surface - interacts with presenilin 1 & presenilin 2 - may play a role in the regulation of PSEN2 proteolytic processing & apoptosis - together with PSEN2 involved in modulation of beta-amyloid formation palmitoylated - palmitoylation enhances association with the plasma membrane (putative) - proteolytically cleaved by caspase-3 - phosphorylation at Ser-63 inhibits cleavage by CASP3 - binds to DNA as a homomultimer - dimerization is induced by binding to Ca+2 - component of heteromultimeric K+ channels - interacts with KCND2 & KCND3 (putative) - interacts with the C-terminus of PSEN1 & PSEN2 & with PSEN2 CTF subunit - associates with KCN1 Structure: - belongs to the recoverin family a) ~25% identical to recoverin b) ~29% identical to hippocalcin c) ~33% identical to neuronal calcium sensor-1 (NCS-1) - contains 4 EF-hand domains Compartment: - cytoplasm, cell membrane, lipid-anchor - colocalizes with presenilin 2 on membranes - endoplasmic reticulum, Golgi, nucleus - associated with plasma membrane (putative) - in the presence of PSEN2, associated with the endoplasmic reticulum & Golgi Expression: - highly expressed in brain - lower in other tissues Pathology: - expression levels are elevated in brain cortex regions affected by Alzheimer disease

Related

neuron-specific Ca+2-binding protein hippocalcin; Ca+2-binding protein BDR-2 (HPCA, BDR2) neuronal Ca+2 sensor 1; NCS-1; frequenin homolog; frequenin-like protein; frequenin-like ubiquitous protein (NCS1, FLUP, FREQ) presenilin recoverin; cancer-associated retinopathy protein; protein CAR; visinin; frequinin; S-modulin (RCVRN, RCV1)

General

Ca+2 binding protein oligomerizing protein phosphoprotein transcriptional silencer (transcriptional repressor)

Properties

SIZE: entity length = 256 aa MW = 29 kD COMPARTMENT: cytoplasm cell nucleus golgi endoplasmic reticulum MOTIF: cysteine residue {C45} MODIFICATION: palmitate COMPARTMENT: membrane cysteine residue {C46} MODIFICATION: palmitate COMPARTMENT: membrane Ser phosphorylation site {S63} EF hand SITE: 67-123 EF hand SITE: 126-161 EF hand SITE: 162-197 MOTIF: Ca+2-binding site SITE: 175-186 EF hand SITE: 210-245 MOTIF: Ca+2-binding site SITE: 223-234 KCND2 interaction {243-256}

Database Correlations

OMIM 604662 UniProt Q9Y2W7 Entrez Gene 30818 Kegg hsa:30818

References

  1. Buxbaum JD et al Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nature Medicine 4:1177-81, 1998 PMID: 9771752
  2. UniProt :accession Q9Y2W7
  3. Cheng HY et al DREAM is a critical transcriptional repressor for pain modulation. Cell 108:31-43, 2002 PMID: 11792319
  4. Carrion AM et al DREAM is a Ca2+-regulated transcriptional repressor. Nature 398:80-4, 1999 PMID: 10078534