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| | <StructureSection load='5lhz' size='340' side='right'caption='[[5lhz]], [[Resolution|resolution]] 2.51Å' scene=''> | | <StructureSection load='5lhz' size='340' side='right'caption='[[5lhz]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lhz]] is a 6 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=5LHZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LHZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lhz]] is a 6 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=5LHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LHZ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLK4, SAK, STK18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), STIL, SIL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.51Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </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=5lhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhz OCA], [https://pdbe.org/5lhz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lhz RCSB], [https://www.ebi.ac.uk/pdbsum/5lhz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhz ProSAT]</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=5lhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhz OCA], [http://pdbe.org/5lhz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lhz RCSB], [http://www.ebi.ac.uk/pdbsum/5lhz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/STIL_HUMAN STIL_HUMAN]] Precursor T-cell acute lymphoblastic leukemia;Autosomal recessive primary microcephaly. A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 slicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLK4_HUMAN PLK4_HUMAN]] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref> [[http://www.uniprot.org/uniprot/STIL_HUMAN STIL_HUMAN]] Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1.<ref>PMID:16024801</ref> <ref>PMID:9372240</ref> | + | [https://www.uniprot.org/uniprot/PLK4_HUMAN PLK4_HUMAN] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref> |
| | <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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polo kinase]]
| + | [[Category: Cottee MA]] |
| - | [[Category: Cottee, M A]] | + | [[Category: Lea SM]] |
| - | [[Category: Lea, S M]] | + | |
| - | [[Category: Centriole]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Polo box domain]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PLK4_HUMAN Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
A small number of proteins form a conserved pathway of centriole duplication. In humans and flies, the binding of Plk4/Sak to STIL/Ana2 initiates daughter centriole assembly. In humans, this interaction is mediated by an interaction between the Polo-Box-3 (PB3) domain of Plk4 and the coiled-coil domain of STIL (HsCCD). We showed previously that the Drosophila Ana2 coiled-coil domain (DmCCD) is essential for centriole assembly, but it forms a tight parallel tetramer in vitro that likely precludes an interaction with PB3. Here we show that the isolated HsCCD and HsPB3 domains form a mixture of homo-multimers in vitro, but these readily dissociate when mixed to form the previously described 1:1 HsCCD:HsPB3 complex. In contrast, although Drosophila PB3 (DmPB3) adopts a canonical polo-box fold, it does not detectably interact with DmCCD in vitro Thus, surprisingly, a key centriole assembly interaction interface appears to differ between humans and flies.
A key centriole assembly interaction interface between human Plk4 and STIL appears to not be conserved in flies.,Cottee MA, Johnson S, Raff JW, Lea SM Biol Open. 2017 Feb 15. pii: bio.024661. doi: 10.1242/bio.024661. PMID:28202467[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005 Dec 20;15(24):2199-207. Epub 2005 Dec 1. PMID:16326102 doi:http://dx.doi.org/10.1016/j.cub.2005.11.042
- ↑ Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005 Nov;7(11):1140-6. PMID:16244668 doi:http://dx.doi.org/10.1038/ncb1320
- ↑ Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002
- ↑ Bonni S, Ganuelas ML, Petrinac S, Hudson JW. Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008 Feb 15;7(4):545-7. Epub 2007 Nov 25. PMID:18239451
- ↑ Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW. Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. PMID:19164942
- ↑ Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP, Hoffmann I, Gonczy P, Malek NP. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011 Jul 3;13(8):1004-9. doi: 10.1038/ncb2282. PMID:21725316 doi:http://dx.doi.org/10.1038/ncb2282
- ↑ Cottee MA, Johnson S, Raff JW, Lea SM. A key centriole assembly interaction interface between human Plk4 and STIL appears to not be conserved in flies. Biol Open. 2017 Feb 15. pii: bio.024661. doi: 10.1242/bio.024661. PMID:28202467 doi:http://dx.doi.org/10.1242/bio.024661
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