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| | <StructureSection load='5lhw' size='340' side='right'caption='[[5lhw]], [[Resolution|resolution]] 0.91Å' scene=''> | | <StructureSection load='5lhw' size='340' side='right'caption='[[5lhw]], [[Resolution|resolution]] 0.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lhw]] 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=5LHW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LHW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lhw]] is a 1 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=5LHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LHW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</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]] 0.91Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STIL, SIL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene></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=5lhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhw OCA], [http://pdbe.org/5lhw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lhw RCSB], [http://www.ebi.ac.uk/pdbsum/5lhw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhw 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=5lhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhw OCA], [https://pdbe.org/5lhw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lhw RCSB], [https://www.ebi.ac.uk/pdbsum/5lhw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [https://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/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/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> |
| | <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: Cottee, M A]] | + | [[Category: Cottee MA]] |
| - | [[Category: Lea, S M]] | + | [[Category: Lea SM]] |
| - | [[Category: Centriole]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Disease
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
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.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Campaner S, Kaldis P, Izraeli S, Kirsch IR. Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint. Mol Cell Biol. 2005 Aug;25(15):6660-72. PMID:16024801 doi:http://dx.doi.org/10.1128/MCB.25.15.6660-6672.2005
- ↑ Izraeli S, Colaizzo-Anas T, Bertness VL, Mani K, Aplan PD, Kirsch IR. Expression of the SIL gene is correlated with growth induction and cellular proliferation. Cell Growth Differ. 1997 Nov;8(11):1171-9. PMID:9372240
- ↑ 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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