Calsenilin

Kv channel interacting protein 3, calsenilin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2E6W​
Identifiers
Symbols	KCNIP3 ; CSEN; DREAM; KCHIP3
External IDs	OMIM: 604662 MGI: 1929258 HomoloGene: 8382 GeneCards: KCNIP3 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • transcription corepressor activity • voltage-gated ion channel activity • potassium channel activity • calcium ion binding • protein binding • protein C-terminus binding • potassium channel regulator activity • calcium-dependent protein binding Cellular component • nucleus • endoplasmic reticulum • Golgi apparatus • cytosol • voltage-gated potassium channel complex Biological process • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • apoptotic process • signal transduction • sensory perception of pain • regulation of neuron apoptotic process • behavioral response to pain • potassium ion transmembrane transport • protein localization to plasma membrane • regulation of potassium ion transmembrane transport Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	30818	56461
Ensembl	ENSG00000115041	ENSMUSG00000079056
UniProt	Q9Y2W7	Q9QXT8
RefSeq (mRNA)	NM_001034914	NM_001111331
RefSeq (protein)	NP_001030086	NP_001104801
Location (UCSC)	Chr 2: 95.3 – 95.39 Mb	Chr 2: 127.46 – 127.52 Mb
PubMed search

Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.^[1][2][3]

Function

This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the neuronal calcium sensor family of proteins.^[4][5] Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. Alternatively spliced transcript variants encoding different isoforms have been described.^[3]

Interactions

Calsenilin has been shown to interact with PSEN1^[1][6] and PSEN2.^[1][7]

See also

• Voltage-gated potassium channel

References

1. Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat Med 4 (10): 1177–81. doi:10.1038/2673. PMID 9771752.
2. Carrión AM, Link WA, Ledo F, Mellström B, Naranjo JR (March 1999). "DREAM is a Ca2+-regulated transcriptional repressor". Nature 398 (6722): 80–4. doi:10.1038/18044. PMID 10078534.
3. "Entrez Gene: KCNIP3 Kv channel interacting protein 3, calsenilin".
4. Burgoyne RD (2007). "Neuronal Calcium Sensor Proteins: Generating Diversity in Neuronal Ca2+ Signalling". Nat. Rev. Neurosci. 8 (3): 182–193. doi:10.1038/nrn2093. PMC 1887812. PMID 17311005.
5. Burgoyne RD, O'Callaghan DW, Hasdemir B, Haynes LP, Tepikin AV (2004). "Neuronal Ca2+-sensor proteins: multitalented regulators of neuronal function". Trends Neurosci. 27 (4): 203–9. doi:10.1016/j.tins.2004.01.010. PMID 15046879.
6. Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, Dargusch R, Schubert D, Kimura H (July 2000). "Isolation and characterization of novel presenilin binding protein". J. Neurochem. 75 (1): 109–16. doi:10.1046/j.1471-4159.2000.0750109.x. PMID 10854253.
7. Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (June 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424.

Further reading

• Carrión AM, Mellström B, Naranjo JR (1998). "Protein Kinase A-Dependent Derepression of the Human Prodynorphin Gene via Differential Binding to an Intragenic Silencer Element". Mol. Cell. Biol. 18 (12): 6921–9. PMC 109275. PMID 9819380.
• An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ (2000). "Modulation of A-type potassium channels by a family of calcium sensors". Nature 403 (6769): 553–6. doi:10.1038/35000592. PMID 10676964.
• Leissring MA, Yamasaki TR, Wasco W, Buxbaum JD, Parker I, LaFerla FM (2000). "Calsenilin reverses presenilin-mediated enhancement of calcium signaling". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8590–3. doi:10.1073/pnas.97.15.8590. PMC 26992. PMID 10900016.
• Buxbaum JD, Lilliehook C, Chan JY, Go RC, Bassett SS, Tanzi RE, Wasco W, Blacker D (2000). "Genomic structure, expression pattern, and chromosomal localization of the human calsenilin gene: no association between an exonic polymorphism and Alzheimer's disease". Neurosci. Lett. 294 (3): 135–8. doi:10.1016/S0304-3940(00)01553-6. PMID 11072133.
• Ledo F, Carrión AM, Link WA, Mellström B, Naranjo JR (2001). "DREAM-αCREM Interaction via Leucine-Charged Domains Derepresses Downstream Regulatory Element-Dependent Transcription". Mol. Cell. Biol. 20 (24): 9120–6. doi:10.1128/MCB.20.24.9120-9126.2000. PMC 102170. PMID 11094064.
• Jo DG, Kim MJ, Choi YH, Kim IK, Song YH, Woo HN, Chung CW, Jung YK (2001). "Pro-apoptotic function of calsenilin/DREAM/KChIP3". FASEB J. 15 (3): 589–91. doi:10.1096/fj.00-0541fje. PMID 11259376.
• Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424.
• Osawa M, Tong KI, Lilliehook C, Wasco W, Buxbaum JD, Cheng HY, Penninger JM, Ikura M, Ames JB (2001). "Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3". J. Biol. Chem. 276 (44): 41005–13. doi:10.1074/jbc.M105842200. PMID 11535596.
• Cheng HY, Pitcher GM, Laviolette SR, Whishaw IQ, Tong KI, Kockeritz LK, Wada T, Joza NA, Crackower M, Goncalves J, Sarosi I, Woodgett JR, Oliveira-dos-Santos AJ, Ikura M, van der Kooy D, Salter MW, Penninger JM (2002). "DREAM is a critical transcriptional repressor for pain modulation". Cell 108 (1): 31–43. doi:10.1016/S0092-8674(01)00629-8. PMID 11792319.
• Lilliehook C, Chan S, Choi EK, Zaidi NF, Wasco W, Mattson MP, Buxbaum JD (2002). "Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling". Mol. Cell. Neurosci. 19 (4): 552–9. doi:10.1006/mcne.2001.1096. PMID 11988022.
• Takimoto K, Yang EK, Conforti L (2002). "Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels". J. Biol. Chem. 277 (30): 26904–11. doi:10.1074/jbc.M203651200. PMID 12006572.
• Ledo F, Kremer L, Mellström B, Naranjo JR (2002). "Ca2+-dependent block of CREB–CBP transcription by repressor DREAM". EMBO J. 21 (17): 4583–92. doi:10.1093/emboj/cdf440. PMC 126180. PMID 12198160.
• Zaidi NF, Berezovska O, Choi EK, Miller JS, Chan H, Lilliehook C, Hyman BT, Buxbaum JD, Wasco W (2002). "Biochemical and immunocytochemical characterization of calsenilin in mouse brain". Neuroscience 114 (1): 247–63. doi:10.1016/S0306-4522(02)00251-8. PMID 12207970.
• Sanz C, Horita M, Fernandez-Luna JL (2004). "Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells". Haematologica 87 (9): 903–7. PMID 12217801.
• Schrader LA, Anderson AE, Mayne A, Pfaffinger PJ, Sweatt JD (2002). "PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex". J. Neurosci. 22 (23): 10123–33. PMID 12451113.
• Hong YM, Jo DG, Lee MC, Kim SY, Jung YK (2003). "Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients". Neurosci. Lett. 340 (1): 33–6. doi:10.1016/S0304-3940(03)00067-3. PMID 12648752.
• Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS (2003). "A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels". J. Biol. Chem. 278 (38): 36445–54. doi:10.1074/jbc.M306142200. PMID 12829703.
• Venn N, Haynes LP, Burgoyne RD (2008). "Specific effects of KChIP3/calsenilin/DREAM, but not KChIPs 1, 2 and 4, on calcium signalling and regulated secretion in PC12 cells". Biochem. J. 413 (1): 71–80. doi:10.1042/BJ20080441. PMC 2474559. PMID 18393943.

External links

• KCNIP3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• NCS proteins

This article incorporates text from the United States National Library of Medicine, which is in the public domain.