Summary: SCL-interrupting locus protein N-terminus
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|SCL/TAL1 interrupting locus|
|Symbols||; MCPH7; SIL|
|RNA expression pattern|
This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint. It is proposed to regulate Cdc2 kinase activity during spindle checkpoint arrest. Chromosomal deletions that fuse this gene and the adjacent locus commonly occur in T cell leukemias, and are thought to arise through illegitimate V-(D)-J recombination events. Multiple transcript variants encoding different isoforms have been found for this gene.
Homozygous mutations in the STIL gene cause primary microcephaly (small brain) in humans.
- Aplan PD, Lombardi DP, Reaman GH, et al. (1992). "Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia". Blood 79 (5): 1327–33. PMID 1311214.
- Aplan PD, Lombardi DP, Kirsch IR (1991). "Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia". Mol. Cell. Biol. 11 (11): 5462–9. PMC 361915. PMID 1922059.
- Jonsson OG, Kitchens RL, Baer RJ, et al. (1991). "Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia". J. Clin. Invest. 87 (6): 2029–35. doi:10.1172/JCI115232. PMC 296958. PMID 2040693.
- Aplan PD, Lombardi DP, Ginsberg AM, et al. (1991). "Disruption of the human SCL locus by "illegitimate" V-(D)-J recombinase activity". Science 250 (4986): 1426–9. doi:10.1126/science.2255914. PMID 2255914.
- Kikuchi A, Hayashi Y, Kobayashi S, et al. (1993). "Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma". Leukemia 7 (7): 933–8. PMID 8321044.
- Collazo-Garcia N, Scherer P, Aplan PD (1997). "Cloning and characterization of a murine SIL gene". Genomics 30 (3): 506–13. doi:10.1006/geno.1995.1271. PMID 8825637.
- Izraeli S, Colaizzo-Anas T, Bertness VL, et al. (1997). "Expression of the SIL gene is correlated with growth induction and cellular proliferation". Cell Growth Differ. 8 (11): 1171–9. PMID 9372240.
- Göttgens B, Barton LM, Gilbert JG, et al. (2000). "Analysis of vertebrate SCL loci identifies conserved enhancers". Nat. Biotechnol. 18 (2): 181–6. doi:10.1038/72635. PMID 10657125.
- Raghavan SC, Kirsch IR, Lieber MR (2001). "Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints". J. Biol. Chem. 276 (31): 29126–33. doi:10.1074/jbc.M103797200. PMID 11390401.
- Carlotti E, Pettenella F, Amaru R, et al. (2002). "Molecular characterization of a new recombination of the SIL/TAL-1 locus in a child with T-cell acute lymphoblastic leukaemia". Br. J. Haematol. 118 (4): 1011–8. doi:10.1046/j.1365-2141.2002.03747.x. PMID 12199779.
- Karkera JD, Izraeli S, Roessler E, et al. (2003). "The genomic structure, chromosomal localization, and analysis of SIL as a candidate gene for holoprosencephaly". Cytogenet. Genome Res. 97 (1–2): 62–7. doi:10.1159/000064057. PMID 12438740.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Colaizzo-Anas T, Aplan PD (2003). "Cloning and characterization of the SIL promoter". Biochim. Biophys. Acta 1625 (2): 207–13. doi:10.1016/S0167-4781(02)00597-3. PMID 12531481.
- Curry JD, Smith MT (2003). "Measurement of SIL-TAL1 fusion gene transcripts associated with human T-cell lymphocytic leukemia by real-time reverse transcriptase-PCR". Leuk. Res. 27 (7): 575–82. doi:10.1016/S0145-2126(02)00260-6. PMID 12681356.
- Cavé H, Suciu S, Preudhomme C, et al. (2004). "Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951". Blood 103 (2): 442–50. doi:10.1182/blood-2003-05-1495. PMID 14504110.
- Erez A, Perelman M, Hewitt SM, et al. (2004). "Sil overexpression in lung cancer characterizes tumors with increased mitotic activity". Oncogene 23 (31): 5371–7. doi:10.1038/sj.onc.1207685. PMID 15107824.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Campaner S, Kaldis P, Izraeli S, Kirsch IR (2005). "Sil Phosphorylation in a Pin1 Binding Domain Affects the Duration of the Spindle Checkpoint". Mol. Cell. Biol. 25 (15): 6660–72. doi:10.1128/MCB.25.15.6660-6672.2005. PMC 1190358. PMID 16024801.
- Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Kumar A, Girimaji SC, Duvvari MR, Blanton SH (2009): Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. American Journal of Human Genetics 84:286-290.
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SCL-interrupting locus protein N-terminus Provide feedback
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Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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This family is new in this Pfam release.
|Author:||Eberhardt RY, Coggill P, Hetherington K|
|Number in seed:||17|
|Number in full:||97|
|Average length of the domain:||313.50 aa|
|Average identity of full alignment:||46 %|
|Average coverage of the sequence by the domain:||33.79 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||1|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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