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STIL (SCL/TAL1 interrupting locus)

Written2005-10Asher Castiel, Shai Izraeli
Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621

(Note : for Links provided by Atlas : click)

Identity

Other namesSIL
TAL1 (SCL) interrupting locus
HGNC (Hugo) STIL
LocusID (NCBI) 6491
Atlas_Id 524
Location 1p33  [Link to chromosome band 1p33]
Location_base_pair Starts at 47715811 and ends at 47779819 bp from pter ( according to hg19-Feb_2009)  [Mapping STIL.png]
Local_order UMP-CMPK (47511608-47556531);SIL (47427869-47491842); TAL1 (47393984-47407363)
Fusion genes
(updated 2016)
ATPIF1 (1p35.3) / STIL (1p33)STIL (1p33) / TAL1 (1p33)STIL (1p33) / TLX3 (5q35.1)
TAL1 (1p33) / STIL (1p33)
Note 47,427,869 bp from pter; End: 47,491,842 bp from pter; Size: 63,973 bases; Orientation: minus strand

DNA/RNA

 
  Genomic structure of SIL. EcoRI sites (R) are indicated. Exons are as shown; the smaller exons are not drawn to scale.
Description 18 exons distributed over 70 kb. 5' portion of the gene demonstrating alternate exon utilization.

Protein

Description 1287 amino acids, 148KDa protein which is highly conserved in vertebrates only. No homologies to known protein motifs except for conserved Serin/Threonine phosporylation sites.
Expression SIL is an immediate early gene, with ubiquitous expression in proliferating cells and during early embryonic development. SIL protein levels peak during mitosis and are degraded on transition to G1. SIL is phosphorylated in mitosis. It is expressed in multiple cancers. In lung cancer its expression correlates with the expression of mitotic checkpoint genes
Localisation Cytosolic protein
Function SIL knockout mouse embryos die in utero displaying holopresencephaly, randomized left/right asymmetry and marked apoptosis of the neural folds. Genetic evidence showed that SIL is required for the Sonic Hedgehog response pathway. SIL phosphorylation and interactions with PIN1 is required for maintenance of the mitotic checkpoint.
Homology There is no homology to other known proteins.

Mutations

Note No mutations were found in families with hereditary holoprosencephaly.

Implicated in

Note
Entity SIL-TAL1(SCL) fusion.
Note A submicroscopic deletions fuses the promoter of SIL to TAL1 to induce an abnormal expression of TAL1.
Disease T-cell ALL. This TAL1-SIL fusion transcript is found in approximately 25% of T-ALL patients.
Cytogenetics Normal karyotype.
Hybrid/Mutated Gene the promoter region of the SCL gene, a hematopoietic transcription factor, and the coding region of the SIL gene are deleted. The molecular result of this SIL/SCL rearrangement is an interstitial deletion on chromosome 1 that juxtaposes the 5' portion of the SIL gene to the coding region of the SCL gene. A SIL/SCL fusion mRNA is produced, with SIL exon 1 splicing to SCL exon 3 in a head-to-tail fashion. Because these are both 5' untranslated region (UTR) exons, the net result is that SIL promoter and enhancer elements drive the expression of a full length SCL gene product.
 
Schematic representation of SIL/SCL fusion mRNA. The germ line SIL (solid boxes) and SCL (open boxes) genomic structures are shown. The deletion breakpoints are indicated with arrows. The SIL/SCL genomic rearrangement is indicated below. The SIL/SCL fusion mRNA is formed by SIL exon 1 (solid box) splicing to SCL exon 3 (open box) in a head-to-tail fashion.
  
Entity SIL overexpression in lung cancer.
Note SIL is also overexpressed in various solid tumors (melanoma, lymphoma, ovary cancer, breast cancer colon cancer lung and prostate cancer) and leukemic cell lines (Dami-acute megakaryocytic, and K562- erythroid blast crisis of chronic myeloid leukemia).
Disease High expression in non- small cell lung cancer (NSCLC). In addition, high expression levels in lung adenocarcinoma, lung squamous carcinoma and lung small cell carcinoma.
Prognosis SIL expression is associated with cell proliferation. In lung cancer, SIL overexpression is correlated with high mitotic activity.
  

Bibliography

Disruption of the human SCL locus by illegitimate V-(D)-J recombinase activity.
Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness VL, Kirsch IR
Science (New York, N.Y.). 1990 ; 250 (4986) : 1426-1429.
PMID 2255914
 
Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia.
Aplan PD, Lombardi DP, Kirsch IR
Molecular and cellular biology. 1991 ; 11 (11) : 5462-5469.
PMID 1922059
 
Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia.
Aplan PD, Lombardi DP, Reaman GH, Sather HN, Hammond GD, Kirsch IR
Blood. 1992 ; 79 (5) : 1327-1333.
PMID 1311214
 
Expression of the SIL gene is correlated with growth induction and cellular proliferation.
Izraeli S, Colaizzo-Anas T, Bertness VL, Mani K, Aplan PD, Kirsch IR
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1997 ; 8 (11) : 1171-1179.
PMID 9372240
 
The SIL gene is required for mouse embryonic axial development and left-right specification.
Izraeli S, Lowe LA, Bertness VL, Good DJ, Dorward DW, Kirsch IR, Kuehn MR
Nature. 1999 ; 399 (6737) : 691-694.
PMID 10385121
 
Genetic evidence that Sil is required for the Sonic Hedgehog response pathway.
Izraeli S, Lowe LA, Bertness VL, Campaner S, Hahn H, Kirsch IR, Kuehn MR
Genesis (New York, N.Y. : 2000). 2001 ; 31 (2) : 72-77.
PMID 11668681
 
Isolation and characterization of a human novel RAB (RAB39B) gene.
Cheng H, Ma Y, Ni X, Jiang M, Guo L, Ying K, Xie Y, Mao Y
Cytogenetic and genome research. 2002 ; 97 (1-2) : 72-75.
PMID 12438742
 
Cloning and characterization of the SIL promoter.
Colaizzo-Anas T, Aplan PD
Biochimica et biophysica acta. 2003 ; 1625 (2) : 207-213.
PMID 12531481
 
Sil overexpression in lung cancer characterizes tumors with increased mitotic activity.
Erez A, Perelman M, Hewitt SM, Cojacaru G, Goldberg I, Shahar I, Yaron P, Muler I, Campaner S, Amariglio N, Rechavi G, Kirsch IR, Krupsky M, Kaminski N, Izraeli S
Oncogene. 2004 ; 23 (31) : 5371-5377.
PMID 15107824
 
Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint.
Campaner S, Kaldis P, Izraeli S, Kirsch IR
Molecular and cellular biology. 2005 ; 25 (15) : 6660-6672.
PMID 16024801
 

Citation

This paper should be referenced as such :
Castiel, A ; Izraeli, S
SIL (SCL/TAL1 interrupting locus)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):97-99.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SILID524ch1p32.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  del(11)(p12p13) LMO2
T-lineage acute lymphoblastic leukemia (T-ALL)

External links

Nomenclature
HGNC (Hugo)STIL   10879
Cards
AtlasSILID524ch1p32
Entrez_Gene (NCBI)STIL  6491  SCL/TAL1 interrupting locus
AliasesMCPH7; SIL
GeneCards (Weizmann)STIL
Ensembl hg19 (Hinxton)ENSG00000123473 [Gene_View]  chr1:47715811-47779819 [Contig_View]  STIL [Vega]
Ensembl hg38 (Hinxton)ENSG00000123473 [Gene_View]  chr1:47715811-47779819 [Contig_View]  STIL [Vega]
ICGC DataPortalENSG00000123473
TCGA cBioPortalSTIL
AceView (NCBI)STIL
Genatlas (Paris)STIL
WikiGenes6491
SOURCE (Princeton)STIL
Genomic and cartography
GoldenPath hg19 (UCSC)STIL  -     chr1:47715811-47779819 -  1p32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)STIL  -     1p32   [Description]    (hg38-Dec_2013)
EnsemblSTIL - 1p32 [CytoView hg19]  STIL - 1p32 [CytoView hg38]
Mapping of homologs : NCBISTIL [Mapview hg19]  STIL [Mapview hg38]
OMIM181590   612703   
Gene and transcription
Genbank (Entrez)AA897748 AK098445 AK128406 AK307519 BC053615
RefSeq transcript (Entrez)NM_001048166 NM_001282936 NM_001282937 NM_001282938 NM_001282939 NM_003035
RefSeq genomic (Entrez)NC_000001 NC_018912 NG_012126 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)STIL
Cluster EST : UnigeneHs.525198 [ NCBI ]
CGAP (NCI)Hs.525198
Alternative Splicing GalleryENSG00000123473
Gene ExpressionSTIL [ NCBI-GEO ]   STIL [ EBI - ARRAY_EXPRESS ]   STIL [ SEEK ]   STIL [ MEM ]
Gene Expression Viewer (FireBrowse)STIL [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6491
GTEX Portal (Tissue expression)STIL
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15468 (Uniprot)
NextProtQ15468  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15468
Splice isoforms : SwissVarQ15468 (Swissvar)
PhosPhoSitePlusQ15468
Domains : Interpro (EBI)Sil   
Domain families : Pfam (Sanger)STIL_N (PF15253)   
Domain families : Pfam (NCBI)pfam15253   
DMDM Disease mutations6491
Blocks (Seattle)STIL
PDB (SRS)4YYP   
PDB (PDBSum)4YYP   
PDB (IMB)4YYP   
PDB (RSDB)4YYP   
Structural Biology KnowledgeBase4YYP   
SCOP (Structural Classification of Proteins)4YYP   
CATH (Classification of proteins structures)4YYP   
SuperfamilyQ15468
Human Protein AtlasENSG00000123473
Peptide AtlasQ15468
HPRD01627
IPIIPI00745920   IPI00328131   IPI00385310   IPI00641114   IPI00514383   IPI00973723   
Protein Interaction databases
DIP (DOE-UCLA)Q15468
IntAct (EBI)Q15468
FunCoupENSG00000123473
BioGRIDSTIL
STRING (EMBL)STIL
ZODIACSTIL
Ontologies - Pathways
QuickGOQ15468
Ontology : AmiGOembryonic axis specification  in utero embryonic development  neural tube closure  heart looping  protein binding  cytoplasm  centrosome  centriole  cytosol  mitotic spindle organization  smoothened signaling pathway  determination of left/right symmetry  cell proliferation  neural tube development  forebrain development  notochord development  floor plate development  multicellular organism growth  negative regulation of apoptotic process  centrosome duplication  centrosome duplication  protein localization to centrosome  
Ontology : EGO-EBIembryonic axis specification  in utero embryonic development  neural tube closure  heart looping  protein binding  cytoplasm  centrosome  centriole  cytosol  mitotic spindle organization  smoothened signaling pathway  determination of left/right symmetry  cell proliferation  neural tube development  forebrain development  notochord development  floor plate development  multicellular organism growth  negative regulation of apoptotic process  centrosome duplication  centrosome duplication  protein localization to centrosome  
NDEx Network
Atlas of Cancer Signalling NetworkSTIL
Wikipedia pathwaysSTIL
Orthology - Evolution
OrthoDB6491
GeneTree (enSembl)ENSG00000123473
Phylogenetic Trees/Animal Genes : TreeFamSTIL
Homologs : HomoloGeneSTIL
Homology/Alignments : Family Browser (UCSC)STIL
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerSTIL [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)STIL
dbVarSTIL
ClinVarSTIL
1000_GenomesSTIL 
Exome Variant ServerSTIL
ExAC (Exome Aggregation Consortium)STIL (select the gene name)
Genetic variants : HAPMAP6491
Genomic Variants (DGV)STIL [DGVbeta]
Mutations
ICGC Data PortalSTIL 
TCGA Data PortalSTIL 
Broad Tumor PortalSTIL
OASIS PortalSTIL [ Somatic mutations - Copy number]
Cancer Gene: CensusSTIL 
Somatic Mutations in Cancer : COSMICSTIL 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch STIL
DgiDB (Drug Gene Interaction Database)STIL
DoCM (Curated mutations)STIL (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)STIL (select a term)
intoGenSTIL
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)1:47715811-47779819  ENSG00000123473
CONAN: Copy Number AnalysisSTIL 
Mutations and Diseases : HGMDSTIL
OMIM181590    612703   
MedgenSTIL
Genetic Testing Registry STIL
NextProtQ15468 [Medical]
TSGene6491
GENETestsSTIL
Huge Navigator STIL [HugePedia]
snp3D : Map Gene to Disease6491
BioCentury BCIQSTIL
ClinGenSTIL
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6491
Chemical/Pharm GKB GenePA35780
Clinical trialSTIL
Miscellaneous
canSAR (ICR)STIL (select the gene name)
Probes
Litterature
PubMed48 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSTIL
EVEXSTIL
GoPubMedSTIL
iHOPSTIL
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue May 31 15:37:10 CEST 2016

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