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| | <StructureSection load='6jju' size='340' side='right'caption='[[6jju]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='6jju' size='340' side='right'caption='[[6jju]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jju]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JJU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JJU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jju]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JJU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/P-type_Ca(2+)_transporter P-type Ca(2+) transporter], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.2.2.10 7.2.2.10] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jju OCA], [http://pdbe.org/6jju PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jju RCSB], [http://www.ebi.ac.uk/pdbsum/6jju PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jju ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6jju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jju OCA], [https://pdbe.org/6jju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jju RCSB], [https://www.ebi.ac.uk/pdbsum/6jju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jju ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AT2A2_HUMAN AT2A2_HUMAN]] Darier disease;Acrokeratosis verruciformis of Hopf. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/AT2A2_HUMAN AT2A2_HUMAN] Darier disease;Acrokeratosis verruciformis of Hopf. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AT2A2_HUMAN AT2A2_HUMAN]] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle (PubMed:16402920). Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation (By similarity).[UniProtKB:O55143]<ref>PMID:16402920</ref> | + | [https://www.uniprot.org/uniprot/AT2A2_HUMAN AT2A2_HUMAN] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle (PubMed:16402920). Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation (By similarity).[UniProtKB:O55143]<ref>PMID:16402920</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6jju" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6jju" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[ATPase 3D structures|ATPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Inaba, K]] | + | [[Category: Inaba K]] |
| - | [[Category: Inoue, M]] | + | [[Category: Inoue M]] |
| - | [[Category: Sakuta, N]] | + | [[Category: Sakuta N]] |
| - | [[Category: Watanabe, S]] | + | [[Category: Watanabe S]] |
| - | [[Category: Calcium transport]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: P-type atpase]]
| + | |
| Structural highlights
Disease
AT2A2_HUMAN Darier disease;Acrokeratosis verruciformis of Hopf. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
AT2A2_HUMAN This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle (PubMed:16402920). Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation (By similarity).[UniProtKB:O55143][1]
Publication Abstract from PubMed
Sarco/endoplasmic reticulum (ER) Ca(2+)-ATPase 2b (SERCA2b) is a ubiquitously expressed membrane protein that facilitates Ca(2+) uptake from the cytosol to the ER. SERCA2b includes a characteristic 11(th) transmembrane helix (TM11) followed by a luminal tail, but the structural basis of SERCA regulation by these C-terminal segments remains unclear. Here, we determined the crystal structures of SERCA2b and its C-terminal splicing variant SERCA2a, both in the E1-2Ca(2+)-adenylyl methylenediphosphonate (AMPPCP) state. Despite discrepancies with the previously reported structural model of SERCA2b, TM11 was found to be located adjacent to TM10 and to interact weakly with a part of the L8/9 loop and the N-terminal end of TM10, thereby inhibiting the SERCA2b catalytic cycle. Accordingly, mutational disruption of the interactions between TM11 and its neighboring residues caused SERCA2b to display SERCA2a-like ATPase activity. We propose that TM11 serves as a key modulator of SERCA2b activity by fine-tuning the intramolecular interactions with other transmembrane regions.
Structural Basis of Sarco/Endoplasmic Reticulum Ca(2+)-ATPase 2b Regulation via Transmembrane Helix Interplay.,Inoue M, Sakuta N, Watanabe S, Zhang Y, Yoshikaie K, Tanaka Y, Ushioda R, Kato Y, Takagi J, Tsukazaki T, Nagata K, Inaba K Cell Rep. 2019 Apr 23;27(4):1221-1230.e3. doi: 10.1016/j.celrep.2019.03.106. PMID:31018135[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dally S, Bredoux R, Corvazier E, Andersen JP, Clausen JD, Dode L, Fanchaouy M, Gelebart P, Monceau V, Del Monte F, Gwathmey JK, Hajjar R, Chaabane C, Bobe R, Raies A, Enouf J. Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c). Biochem J. 2006 Apr 15;395(2):249-58. doi: 10.1042/BJ20051427. PMID:16402920 doi:http://dx.doi.org/10.1042/BJ20051427
- ↑ Inoue M, Sakuta N, Watanabe S, Zhang Y, Yoshikaie K, Tanaka Y, Ushioda R, Kato Y, Takagi J, Tsukazaki T, Nagata K, Inaba K. Structural Basis of Sarco/Endoplasmic Reticulum Ca(2+)-ATPase 2b Regulation via Transmembrane Helix Interplay. Cell Rep. 2019 Apr 23;27(4):1221-1230.e3. doi: 10.1016/j.celrep.2019.03.106. PMID:31018135 doi:http://dx.doi.org/10.1016/j.celrep.2019.03.106
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