Calsenilin

Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.[5][6][7]

KCNIP3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E6W
Identifiers
Aliases	KCNIP3, CSEN, DREAM, KCHIP3, potassium voltage-gated channel interacting protein 3
External IDs	OMIM: 604662 MGI: 1929258 HomoloGene: 8382 GeneCards: KCNIP3
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q11.1 Start 95,297,327 bp[1] End 95,386,077 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 F1 Start 127,456,498 bp[2] End 127,522,094 bp[2]
Gene ontology Molecular function • DNA binding • calcium ion binding • sequence-specific DNA binding • potassium channel activity • GO:0001106 transcription corepressor activity • voltage-gated ion channel activity • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • GO:0001948 protein binding • potassium channel regulator activity • ion channel binding Cellular component • cytoplasm • axon terminus • cytosol • Golgi apparatus • membrane • voltage-gated potassium channel complex • axon • dendrite • protein-DNA complex • endoplasmic reticulum • cell nucleus • cell membrane Biological process • regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • regulation of ion transmembrane transport • negative regulation of transcription from RNA polymerase II promoter • ion transport • transcription, DNA-templated • potassium ion transport • potassium ion transmembrane transport • protein localization to plasma membrane • intracellular protein transport • regulation of potassium ion transmembrane transport • signal transduction • apoptotic process • negative regulation of nucleic acid-templated transcription • cardiac conduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	30818	56461
Ensembl	ENSG00000115041	ENSMUSG00000079056
UniProt	Q9Y2W7	Q9QXT8 P0C092
RefSeq (mRNA)	NM_001034914 NM_013434	NM_001111331 NM_001291005 NM_019789
RefSeq (protein)	NP_001030086 NP_038462	NP_001104801 NP_001277934 NP_062763
Location (UCSC)	Chr 2: 95.3 – 95.39 Mb	Chr 2: 127.46 – 127.52 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[8][9] 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. In addition, the protein has been shown to transcriptionally repress A20 (TNFAIP3) expression and thus modulate the anti-inflammatory signaling.[10] Alternatively spliced transcript variants encoding different isoforms have been described.[7]

Interactions

Calsenilin has been shown to interact with PSEN1[5][11] and PSEN2.[5][12]

See also

• Voltage-gated potassium channel

References

1. GRCh38: Ensembl release 89: ENSG00000115041 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000079056 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: KCNIP3 Kv channel interacting protein 3, calsenilin".
8. 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.
9. 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.
10. Tiruppathi C, Soni D, Wang DM, et al. (March 2014). "The transcription factor DREAM represses A20 and mediates inflammation". Nat Immunol. 15 (3): 239–247. doi:10.1038/ni.2823. PMC 4005385. PMID 24487321.
11. 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.
12. 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. doi:10.1128/MCB.18.12.6921. 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. doi:10.1523/JNEUROSCI.22-23-10123.2002. PMC 6758737. 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.