| Structural highlights
Function
[CSEN_HUMAN] 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).[1] [2] [3] [4] [5] [6] Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Probably modulates channels density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and probably KCND3 trafficking to the cell surface.[7] [8] [9] [10] [11] [12] May play a role in the regulation of PSEN2 proteolytic processing and apoptosis. Together with PSEN2 involved in modulation of beta-amyloid formation.[13] [14] [15] [16] [17] [18]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Calsenilin is a member of the recoverin branch of the EF-hand superfamily that is reported to interact with presenilins, regulate prodynorphin gene expression, modulate voltage-gated Kv4 potassium channel function, and bind to neurotoxins. Calsenilin is a Ca+2-binding protein and plays an important role in calcium signaling. Despite its importance in numerous neurological functions, the structure of this protein has not been reported. In the absence of Ca+2, the protein has limited spectral resolution that increases upon the addition of Ca+2. Here, we describe the three-dimensional solution structure of EF-hands 3 and 4 of calsenilin in the Ca+2-bound form. The Ca+2-bound structure consists of five alpha-helices and one two-stranded antiparallel beta-sheet. The long loop that connects EF hands 3 and 4 is highly disordered in solution. In addition to its structural effects, Ca+2 binding also increases the protein's propensity to dimerize. These changes in structure and oligomerization state induced upon Ca+2 binding may play important roles in molecular recognition during calcium signaling.
Solution structure and calcium-binding properties of EF-hands 3 and 4 of calsenilin.,Yu L, Sun C, Mendoza R, Wang J, Matayoshi ED, Hebert E, Pereda-Lopez A, Hajduk PJ, Olejniczak ET Protein Sci. 2007 Nov;16(11):2502-9. PMID:17962406[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W. Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nat Med. 1998 Oct;4(10):1177-81. PMID:9771752 doi:http://dx.doi.org/10.1038/2673
- ↑ Carrion AM, Link WA, Ledo F, Mellstrom B, Naranjo JR. DREAM is a Ca2+-regulated transcriptional repressor. Nature. 1999 Mar 4;398(6722):80-4. PMID:10078534 doi:http://dx.doi.org/10.1038/18044
- ↑ An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ. Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000 Feb 3;403(6769):553-6. PMID:10676964 doi:10.1038/35000592
- ↑ Jo DG, Kim MJ, Choi YH, Kim IK, Song YH, Woo HN, Chung CW, Jung YK. Pro-apoptotic function of calsenilin/DREAM/KChIP3. FASEB J. 2001 Mar;15(3):589-91. Epub 2001 Jan 19. PMID:11259376 doi:http://dx.doi.org/10.1096/fj.00-0541fje
- ↑ Lilliehook C, Chan S, Choi EK, Zaidi NF, Wasco W, Mattson MP, Buxbaum JD. Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling. Mol Cell Neurosci. 2002 Apr;19(4):552-9. PMID:11988022 doi:http://dx.doi.org/10.1006/mcne.2001.1096
- ↑ Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS. A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. J Biol Chem. 2003 Sep 19;278(38):36445-54. Epub 2003 Jun 26. PMID:12829703 doi:10.1074/jbc.M306142200
- ↑ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W. Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nat Med. 1998 Oct;4(10):1177-81. PMID:9771752 doi:http://dx.doi.org/10.1038/2673
- ↑ Carrion AM, Link WA, Ledo F, Mellstrom B, Naranjo JR. DREAM is a Ca2+-regulated transcriptional repressor. Nature. 1999 Mar 4;398(6722):80-4. PMID:10078534 doi:http://dx.doi.org/10.1038/18044
- ↑ An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ. Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000 Feb 3;403(6769):553-6. PMID:10676964 doi:10.1038/35000592
- ↑ Jo DG, Kim MJ, Choi YH, Kim IK, Song YH, Woo HN, Chung CW, Jung YK. Pro-apoptotic function of calsenilin/DREAM/KChIP3. FASEB J. 2001 Mar;15(3):589-91. Epub 2001 Jan 19. PMID:11259376 doi:http://dx.doi.org/10.1096/fj.00-0541fje
- ↑ Lilliehook C, Chan S, Choi EK, Zaidi NF, Wasco W, Mattson MP, Buxbaum JD. Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling. Mol Cell Neurosci. 2002 Apr;19(4):552-9. PMID:11988022 doi:http://dx.doi.org/10.1006/mcne.2001.1096
- ↑ Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS. A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. J Biol Chem. 2003 Sep 19;278(38):36445-54. Epub 2003 Jun 26. PMID:12829703 doi:10.1074/jbc.M306142200
- ↑ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W. Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nat Med. 1998 Oct;4(10):1177-81. PMID:9771752 doi:http://dx.doi.org/10.1038/2673
- ↑ Carrion AM, Link WA, Ledo F, Mellstrom B, Naranjo JR. DREAM is a Ca2+-regulated transcriptional repressor. Nature. 1999 Mar 4;398(6722):80-4. PMID:10078534 doi:http://dx.doi.org/10.1038/18044
- ↑ An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ. Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000 Feb 3;403(6769):553-6. PMID:10676964 doi:10.1038/35000592
- ↑ Jo DG, Kim MJ, Choi YH, Kim IK, Song YH, Woo HN, Chung CW, Jung YK. Pro-apoptotic function of calsenilin/DREAM/KChIP3. FASEB J. 2001 Mar;15(3):589-91. Epub 2001 Jan 19. PMID:11259376 doi:http://dx.doi.org/10.1096/fj.00-0541fje
- ↑ Lilliehook C, Chan S, Choi EK, Zaidi NF, Wasco W, Mattson MP, Buxbaum JD. Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling. Mol Cell Neurosci. 2002 Apr;19(4):552-9. PMID:11988022 doi:http://dx.doi.org/10.1006/mcne.2001.1096
- ↑ Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS. A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. J Biol Chem. 2003 Sep 19;278(38):36445-54. Epub 2003 Jun 26. PMID:12829703 doi:10.1074/jbc.M306142200
- ↑ Yu L, Sun C, Mendoza R, Wang J, Matayoshi ED, Hebert E, Pereda-Lopez A, Hajduk PJ, Olejniczak ET. Solution structure and calcium-binding properties of EF-hands 3 and 4 of calsenilin. Protein Sci. 2007 Nov;16(11):2502-9. PMID:17962406 doi:16/11/2502
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