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| | <StructureSection load='6w36' size='340' side='right'caption='[[6w36]], [[Resolution|resolution]] 2.85Å' scene=''> | | <StructureSection load='6w36' size='340' side='right'caption='[[6w36]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6w36]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W36 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W36 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w36]] 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=6W36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W36 FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TENT5C, FAM46C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TENT5C, FAM46C ([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'>[http://en.wikipedia.org/wiki/Polynucleotide_adenylyltransferase Polynucleotide adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.19 2.7.7.19] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Polynucleotide_adenylyltransferase Polynucleotide adenylyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.19 2.7.7.19] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w36 OCA], [http://pdbe.org/6w36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w36 RCSB], [http://www.ebi.ac.uk/pdbsum/6w36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w36 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=6w36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w36 OCA], [https://pdbe.org/6w36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w36 RCSB], [https://www.ebi.ac.uk/pdbsum/6w36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w36 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TET5C_HUMAN TET5C_HUMAN]] Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.<ref>PMID:27060136</ref> <ref>PMID:28931820</ref> (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.<ref>PMID:21478870</ref> | + | [[https://www.uniprot.org/uniprot/TET5C_HUMAN TET5C_HUMAN]] Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.<ref>PMID:27060136</ref> <ref>PMID:28931820</ref> (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.<ref>PMID:21478870</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
Function
[TET5C_HUMAN] Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.[1] [2] (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.[3]
Publication Abstract from PubMed
FAM46C, a non-canonical poly(A) polymerase, is frequently mutated in multiple myeloma. Loss of function of FAM46C promotes cell survival of multiple myeloma, suggesting a tumor-suppressive role. FAM46C is also essential for fastening sperm head and flagellum, indispensable for male fertility. The molecular mechanisms of these functions of FAM46C remain elusive. We report the crystal structure of FAM46C to provide the basis for its poly(A) polymerase activity and rationalize mutations associated with multiple myeloma. In addition, we found that FAM46C interacts directly with the serine/threonine kinase Plk4, the master regulator of centrosome duplication. We present the structure of FAM46C in complex with the Cryptic Polo-Box 1-2 domains of Plk4. Our structure-based mutational analyses show that the interaction with Plk4 recruits FAM46C to centrosomes. Our data suggest that Plk4-mediated localization of FAM46C enables its regulation of centrosome structure and functions, which may underlie the roles for FAM46C in cell proliferation and sperm development.
Structural and Functional Analyses of the FAM46C/Plk4 Complex.,Chen H, Lu D, Shang G, Gao G, Zhang X Structure. 2020 May 12. pii: S0969-2126(20)30169-6. doi:, 10.1016/j.str.2020.04.023. PMID:32433990[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kuchta K, Muszewska A, Knizewski L, Steczkiewicz K, Wyrwicz LS, Pawlowski K, Rychlewski L, Ginalski K. FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases. Nucleic Acids Res. 2016 May 5;44(8):3534-48. doi: 10.1093/nar/gkw222. Epub 2016, Apr 7. PMID:27060136 doi:http://dx.doi.org/10.1093/nar/gkw222
- ↑ Mroczek S, Chlebowska J, Kulinski TM, Gewartowska O, Gruchota J, Cysewski D, Liudkovska V, Borsuk E, Nowis D, Dziembowski A. The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma. Nat Commun. 2017 Sep 20;8(1):619. doi: 10.1038/s41467-017-00578-5. PMID:28931820 doi:http://dx.doi.org/10.1038/s41467-017-00578-5
- ↑ Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10. PMID:21478870 doi:10.1038/nature09907
- ↑ Chen H, Lu D, Shang G, Gao G, Zhang X. Structural and Functional Analyses of the FAM46C/Plk4 Complex. Structure. 2020 May 12. pii: S0969-2126(20)30169-6. doi:, 10.1016/j.str.2020.04.023. PMID:32433990 doi:http://dx.doi.org/10.1016/j.str.2020.04.023
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