calsenilin; Kv channel-interacting protein 3; KChIP3; A-type K+ channel modulatory protein 3; DRE-antagonist modulator; DREAM (KCNIP3, CSEN, DREAM, KCHIP3)
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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
- ~25% identical to recoverin
- ~29% identical to hippocalcin
- ~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
More general terms
- Ca+2 binding protein
- transcriptional silencer (transcriptional repressor)
- oligomerizing protein
- phosphoprotein
Additional terms
- 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)
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/9771752
- ↑ UniProt http://www.uniprot.org/uniprot/Q9Y2W7.html
- ↑ Cheng HY et al DREAM is a critical transcriptional repressor for pain modulation. Cell 108:31-43, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11792319
- ↑ Carrion AM et al DREAM is a Ca2+-regulated transcriptional repressor. Nature 398:80-4, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10078534