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| | ==Crystal structure of Sec23a/Sec24a/Sec22 complexed with 4-phenylbutyric acid (15mM soaking)== | | ==Crystal structure of Sec23a/Sec24a/Sec22 complexed with 4-phenylbutyric acid (15mM soaking)== |
| - | <StructureSection load='5vnm' size='340' side='right' caption='[[5vnm]], [[Resolution|resolution]] 2.77Å' scene=''> | + | <StructureSection load='5vnm' size='340' side='right'caption='[[5vnm]], [[Resolution|resolution]] 2.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vnm]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VNM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vnm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VNM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLT:4-PHENYL-BUTANOIC+ACID'>CLT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.765Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vne|5vne]], [[5vnf|5vnf]], [[5vng|5vng]], [[5vnh|5vnh]], [[5vni|5vni]], [[5vnj|5vnj]], [[5vnk|5vnk]], [[5vnl|5vnl]], [[5vnn|5vnn]], [[5vno|5vno]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLT:4-PHENYL-BUTANOIC+ACID'>CLT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SEC23A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC24A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Sec22b, Sec22l1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5vnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnm OCA], [https://pdbe.org/5vnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vnm RCSB], [https://www.ebi.ac.uk/pdbsum/5vnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnm ProSAT]</span></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=5vnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnm OCA], [http://pdbe.org/5vnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vnm RCSB], [http://www.ebi.ac.uk/pdbsum/5vnm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN]] Defects in SEC23A are the cause of craniolenticulosutural dysplasia (CLSD) [MIM:[http://omim.org/entry/607812 607812]]; also known as cranio-lenticulo-sutural dysplasia. CLSD is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.<ref>PMID:16980979</ref> | + | [https://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN] Defects in SEC23A are the cause of craniolenticulosutural dysplasia (CLSD) [MIM:[https://omim.org/entry/607812 607812]; also known as cranio-lenticulo-sutural dysplasia. CLSD is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.<ref>PMID:16980979</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN]] Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex. [[http://www.uniprot.org/uniprot/SC22B_MOUSE SC22B_MOUSE]] SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER. [[http://www.uniprot.org/uniprot/SC24A_HUMAN SC24A_HUMAN]] Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex. | + | [https://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN] Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Goldberg, J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ma, W]] | + | [[Category: Goldberg J]] |
| - | [[Category: Copii]] | + | [[Category: Ma W]] |
| - | [[Category: Er retention]]
| + | |
| - | [[Category: P24]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Trafficking]]
| + | |
| Structural highlights
Disease
SC23A_HUMAN Defects in SEC23A are the cause of craniolenticulosutural dysplasia (CLSD) [MIM:607812; also known as cranio-lenticulo-sutural dysplasia. CLSD is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.[1]
Function
SC23A_HUMAN Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex.
Publication Abstract from PubMed
Native cargo proteins exit the endoplasmic reticulum (ER) in COPII-coated vesicles, whereas resident and misfolded proteins are substantially excluded from vesicles by a retention mechanism that remains unresolved. We probed the ER retention process using the proteostasis regulator 4-phenylbutyrate (4-PBA), which we show targets COPII protein to reduce the stringency of retention. 4-PBA competes with p24 proteins to bind COPII. When p24 protein uptake is blocked, COPII vesicles package resident proteins and an ER-trapped mutant LDL receptor. We further show that 4-PBA triggers the secretion of a KDEL-tagged luminal resident, implying that a compromised retention mechanism causes saturation of the KDEL retrieval system. The results indicate that stringent ER retention requires the COPII coat machinery to actively sort biosynthetic cargo from diffusible misfolded and resident ER proteins.
ER retention is imposed by COPII protein sorting and attenuated by 4-phenylbutyrate.,Ma W, Goldberg E, Goldberg J Elife. 2017 Jun 8;6. pii: e26624. doi: 10.7554/eLife.26624. PMID:28594326[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Boyadjiev SA, Fromme JC, Ben J, Chong SS, Nauta C, Hur DJ, Zhang G, Hamamoto S, Schekman R, Ravazzola M, Orci L, Eyaid W. Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking. Nat Genet. 2006 Oct;38(10):1192-7. Epub 2006 Sep 17. PMID:16980979 doi:10.1038/ng1876
- ↑ Ma W, Goldberg E, Goldberg J. ER retention is imposed by COPII protein sorting and attenuated by 4-phenylbutyrate. Elife. 2017 Jun 8;6. pii: e26624. doi: 10.7554/eLife.26624. PMID:28594326 doi:http://dx.doi.org/10.7554/eLife.26624
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