7e7s

<table><tr><td colspan='2'>[[7e7s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E7S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E7S FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATP2A2, ATP2B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/P-type_Ca(2+)_transporter P-type Ca(2+) transporter], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.2.2.10 7.2.2.10] </span></td></tr>

== Disease ==

[[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 ==

[[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>

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== Publication Abstract from PubMed ==

Sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) 2b is a ubiquitous SERCA family member that conducts Ca(2+) uptake from the cytosol to the ER. Herein, we present a 3.3 A resolution cryo-electron microscopy (cryo-EM) structure of human SERCA2b in the E1.2Ca(2+) state, revealing a new conformation for Ca(2+) -bound SERCA2b with a much closer arrangement of cytosolic domains than in the previously reported crystal structure of Ca(2+) -bound SERCA1a. Multiple conformations generated by 3D classification of cryo-EM maps reflect the intrinsically dynamic nature of the cytosolic domains in this state. Notably, ATP binding residues of SERCA2b in the E1.2Ca(2+) state are located at similar positions to those in the E1.2Ca(2+) -ATP state; hence, the cryo-EM structure likely represents a preformed state immediately prior to ATP binding. Consistently, a SERCA2b mutant with an interdomain disulfide bridge that locks the closed cytosolic domain arrangement displayed significant autophosphorylation activity in the presence of Ca(2+) . We propose a novel mechanism of ATP binding to SERCA2b.

Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca(2+) -ATPase SERCA2b.,Zhang Y, Watanabe S, Tsutsumi A, Kadokura H, Kikkawa M, Inaba K EMBO J. 2021 Oct 1;40(19):e108482. doi: 10.15252/embj.2021108482. Epub 2021 Aug, 30. PMID:34459010<ref>PMID:34459010</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Human]]

[[Category: Inaba, K]]

[[Category: Tsutsumi, A]]

[[Category: Watanabe, S]]

[[Category: Zhang, Y]]

[[Category: Metal transport]]