8tzp: Difference between revisions

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</table>

== Disease ==

[https://www.uniprot.org/uniprot/~~WLS_HUMAN WLS_HUMAN~~] The disease is caused by ~~variants~~ affecting the gene represented in this entry.

[https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Phocomelia, Schinzel type;Fuhrmann syndrome. 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/~~WLS_HUMAN WLS_HUMAN~~] ~~Regulates~~ Wnt proteins ~~sorting~~ and secretion ~~in a feedback regulatory mechanism~~. ~~This reciprocal interaction plays~~ a ~~key role~~ in the ~~regulation~~ of ~~expression~~, ~~subcellular location~~, ~~binding~~ and ~~organelle~~-~~specific~~ association of ~~Wnt proteins~~ (~~PubMed:34587386~~). ~~Plays also an important role in establishment~~ of ~~the anterior~~-~~posterior body axis formation during development~~ (~~By similarity~~).<ref>PMID:~~16678095~~</ref> <~~ref~~>~~PMID:16678096~~</~~ref~~> <~~ref~~>~~PMID:34587386~~</~~ref~~>

[https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Signaling by Wnt-7a allows sexually dimorphic development of the mullerian ducts (By similarity).

== Publication Abstract from PubMed ==

Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK(CC4) engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.

Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.,Qi X, Hu Q, Elghobashi-Meinhardt N, Long T, Chen H, Li X Cell. 2023 Nov 9;186(23):5028-5040.e14. doi: 10.1016/j.cell.2023.09.021. Epub , 2023 Oct 17. PMID:37852257<ref>PMID:37852257</ref>

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

</div>

== References ==

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@@ Line 9: / Line 9: @@
 </table>
 == Disease ==
-[https://www.uniprot.org/uniprot/WLS_HUMAN WLS_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Phocomelia, Schinzel type;Fuhrmann syndrome. 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/WLS_HUMAN WLS_HUMAN] Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins (PubMed:34587386). Plays also an important role in establishment of the anterior-posterior body axis formation during development (By similarity).<ref>PMID:16678095</ref> <ref>PMID:16678096</ref> <ref>PMID:34587386</ref>
+[https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Signaling by Wnt-7a allows sexually dimorphic development of the mullerian ducts (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK(CC4) engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.
+Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.,Qi X, Hu Q, Elghobashi-Meinhardt N, Long T, Chen H, Li X Cell. 2023 Nov 9;186(23):5028-5040.e14. doi: 10.1016/j.cell.2023.09.021. Epub , 2023 Oct 17. PMID:37852257<ref>PMID:37852257</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8tzp" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>