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TSC2 (tuberous sclerosis 2)

Identity

HGNC (Hugo) TSC2
LocusID (NCBI) 7249
Location 16p13.3
Location_base_pair Starts at 2097990 and ends at 2138713 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description 41 exons; spans 41kb
Transcription At least 3 alternate splicings; 5.5kb mRNA complete cds; coding sequence: CDS 19-5442

Protein

Description Tuberin; 1807 amino acids; 190 kDaltons
Expression Expressed in most embryonic and adult tissues
Localisation Cytoplasmic
Function Potential GTPase activating protein (GAP) for Rap1a and/or Rab5; Interacts with hamartin ( TSC1 gene product) and Rabaptin-5
Homology 188 residues at the COOH terminus have homology to Rap/Ran GAP

Mutations

Germinal Large genomic deletions in <10% of cases; point mutations widely dispersed, with no cluster; truncating effect in 2/3 of cases
Somatic loss-of-heterozygosity in 2/3 of renal angiomyolipomas; Somatic mutations in angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM) cells from women with sporadic LAM

Implicated in

Entity Tuberous Sclerosis Comples (TSC)
Disease Autosomal dominant disease characterized by seizures, mental retardation, autism, benign tumors of the brain, heart, skin, kidney, and malignant kidney tumors.
  
Entity Sporadic lymphangioleiomyomatosis (LAM)
Disease Lung disease affecting almost exclusively women, characterized by diffuse bilateral proliferation of abnormal smooth muscle cells in the lungs
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

External links

Nomenclature
HGNC (Hugo)TSC2   12363
Cards
AtlasTSC2ID184
Entrez_Gene (NCBI)TSC2  7249  tuberous sclerosis 2
GeneCards (Weizmann)TSC2
Ensembl (Hinxton)ENSG00000103197 [Gene_View]  chr16:2097990-2138713 [Contig_View]  TSC2 [Vega]
ICGC DataPortalENSG00000103197
cBioPortalTSC2
AceView (NCBI)TSC2
Genatlas (Paris)TSC2
WikiGenes7249
SOURCE (Princeton)NM_000548 NM_001077183 NM_001114382 NM_021055 NM_021056
Genomic and cartography
GoldenPath (UCSC)TSC2  -  16p13.3   chr16:2097990-2138713 +  16p13.3   [Description]    (hg19-Feb_2009)
EnsemblTSC2 - 16p13.3 [CytoView]
Mapping of homologs : NCBITSC2 [Mapview]
OMIM191092   606690   613254   
Gene and transcription
Genbank (Entrez)AB210000 AK022401 AK094152 AK125096 AK295672
RefSeq transcript (Entrez)NM_000548 NM_001077183 NM_001114382 NM_021055 NM_021056
RefSeq genomic (Entrez)AC_000148 NC_000016 NC_018927 NG_005895 NT_010393 NW_001838339 NW_004929400
Consensus coding sequences : CCDS (NCBI)TSC2
Cluster EST : UnigeneHs.90303 [ NCBI ]
CGAP (NCI)Hs.90303
Alternative Splicing : Fast-db (Paris)GSHG0010857
Alternative Splicing GalleryENSG00000103197
Gene ExpressionTSC2 [ NCBI-GEO ]     TSC2 [ SEEK ]   TSC2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49815 (Uniprot)
NextProtP49815  [Medical]
With graphics : InterProP49815
Splice isoforms : SwissVarP49815 (Swissvar)
Domaine pattern : Prosite (Expaxy)RAPGAP (PS50085)   
Domains : Interpro (EBI)ARM-like [organisation]   ARM-type_fold [organisation]   Rap_GAP_dom [organisation]   Tuberin [organisation]   Tuberin-type_domain [organisation]   Tuberin_N [organisation]  
Related proteins : CluSTrP49815
Domain families : Pfam (Sanger)DUF3384 (PF11864)    Rap_GAP (PF02145)    Tuberin (PF03542)   
Domain families : Pfam (NCBI)pfam11864    pfam02145    pfam03542   
DMDM Disease mutations7249
Blocks (Seattle)P49815
Human Protein AtlasENSG00000103197 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP49815
HPRD01850
IPIIPI00028493   IPI00218881   IPI00952929   IPI00218883   IPI00954095   IPI00552156   IPI00879496   IPI00877641   IPI00877797   
Protein Interaction databases
DIP (DOE-UCLA)P49815
IntAct (EBI)P49815
FunCoupENSG00000103197
BioGRIDTSC2
InParanoidP49815
Interologous Interaction database P49815
IntegromeDBTSC2
STRING (EMBL)TSC2
Ontologies - Pathways
Ontology : AmiGOresponse to hypoxia  neural tube closure  GTPase activator activity  protein binding  nucleus  nucleus  cytoplasm  cytoplasm  Golgi apparatus  Golgi apparatus  cytosol  cytosol  caveola  negative regulation of protein kinase activity  protein import into nucleus  endocytosis  acute-phase response  cell cycle arrest  epidermal growth factor receptor signaling pathway  heart development  protein localization  negative regulation of cell proliferation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  phosphatidylinositol 3-kinase signaling  negative regulation of phosphatidylinositol 3-kinase signaling  membrane  vesicle-mediated transport  phosphatase binding  cell projection organization  regulation of endocytosis  negative regulation of Wnt signaling pathway  dendrite  growth cone  negative regulation of TOR signaling  positive regulation of Ras GTPase activity  TSC1-TSC2 complex  Fc-epsilon receptor signaling pathway  protein homodimerization activity  neuronal cell body  negative regulation of MAP kinase activity  protein kinase B signaling  innate immune response  negative regulation of cell size  regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  protein heterodimerization activity  insulin-like growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  negative regulation of epithelial cell proliferation  positive chemotaxis  protein homooligomerization  protein heterooligomerization  regulation of cell cycle  negative regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  14-3-3 protein binding  
Ontology : EGO-EBIresponse to hypoxia  neural tube closure  GTPase activator activity  protein binding  nucleus  nucleus  cytoplasm  cytoplasm  Golgi apparatus  Golgi apparatus  cytosol  cytosol  caveola  negative regulation of protein kinase activity  protein import into nucleus  endocytosis  acute-phase response  cell cycle arrest  epidermal growth factor receptor signaling pathway  heart development  protein localization  negative regulation of cell proliferation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  phosphatidylinositol 3-kinase signaling  negative regulation of phosphatidylinositol 3-kinase signaling  membrane  vesicle-mediated transport  phosphatase binding  cell projection organization  regulation of endocytosis  negative regulation of Wnt signaling pathway  dendrite  growth cone  negative regulation of TOR signaling  positive regulation of Ras GTPase activity  TSC1-TSC2 complex  Fc-epsilon receptor signaling pathway  protein homodimerization activity  neuronal cell body  negative regulation of MAP kinase activity  protein kinase B signaling  innate immune response  negative regulation of cell size  regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  protein heterodimerization activity  insulin-like growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  negative regulation of epithelial cell proliferation  positive chemotaxis  protein homooligomerization  protein heterooligomerization  regulation of cell cycle  negative regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  14-3-3 protein binding  
Pathways : BIOCARTAControl of Gene Expression by Vitamin D Receptor [Genes]    mTOR Signaling Pathway [Genes]   
Pathways : KEGGp53 signaling pathway    mTOR signaling pathway    PI3K-Akt signaling pathway    Insulin signaling pathway    Thyroid hormone signaling pathway   
Protein Interaction DatabaseTSC2
Wikipedia pathwaysTSC2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TSC2
snp3D : Map Gene to Disease7249
SNP (GeneSNP Utah)TSC2
SNP : HGBaseTSC2
Genetic variants : HAPMAPTSC2
Exome VariantTSC2
1000_GenomesTSC2 
ICGC programENSG00000103197 
Cancer Gene: CensusTSC2 
Somatic Mutations in Cancer : COSMICTSC2 
CONAN: Copy Number AnalysisTSC2 
Mutations and Diseases : HGMDTSC2
Genomic VariantsTSC2  TSC2 [DGVbeta]
dbVarTSC2
ClinVarTSC2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM191092    606690    613254   
MedgenTSC2
GENETestsTSC2
Disease Genetic AssociationTSC2
Huge Navigator TSC2 [HugePedia]  TSC2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneTSC2
Homology/Alignments : Family Browser (UCSC)TSC2
Phylogenetic Trees/Animal Genes : TreeFamTSC2
Chemical/Protein Interactions : CTD7249
Chemical/Pharm GKB GenePA37035
Clinical trialTSC2
Cancer Resource (Charite)ENSG00000103197
Other databases
Other databasehttp://zk.bwh.harvard.edu/ts/TSC2-19.htm
Probes
Litterature
PubMed288 Pubmed reference(s) in Entrez
CoreMineTSC2
iHOPTSC2
OncoSearchTSC2

Bibliography

Identification and characterization of the tuberous sclerosis gene on chromosome 16.
European Chromosome 16 Tuberous Sclerosis Consortium, European Chromosome 16 Tuberous Sclerosis Consortium
Cell. 1993 ; 75 (7) : 1305-1315.
PMID 8269512
 
9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.
Carbonara C, Longa L, Grosso E, Borrone C, Garrˆ® MG, Brisigotti M, Migone N
Human molecular genetics. 1994 ; 3 (10) : 1829-1832.
PMID 7849708
 
Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.
Green AJ, Smith M, Yates JR
Nature genetics. 1994 ; 6 (2) : 193-196.
PMID 8162074
 
Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas.
Henske EP, Neumann HP, Scheithauer BW, Herbst EW, Short MP, Kwiatkowski DJ
Genes, chromosomes & cancer. 1995 ; 13 (4) : 295-298.
PMID 7547639
 
Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.
Wienecke R, Kˆnig A, DeClue JE
The Journal of biological chemistry. 1995 ; 270 (27) : 16409-16414.
PMID 7608212
 
Role of the tuberous sclerosis gene-2 product in cell cycle control. Loss of the tuberous sclerosis gene-2 induces quiescent cells to enter S phase.
Soucek T, Pusch O, Wienecke R, DeClue JE, Hengstschlˆ§ger M
The Journal of biological chemistry. 1997 ; 272 (46) : 29301-29308.
PMID 9361010
 
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.
Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS
The Journal of biological chemistry. 1997 ; 272 (10) : 6097-6100.
PMID 9045618
 
Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members.
Henry KW, Yuan X, Koszewski NJ, Onda H, Kwiatkowski DJ, Noonan DJ
The Journal of biological chemistry. 1998 ; 273 (32) : 20535-20539.
PMID 9685410
 
Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.
Plank TL, Yeung RS, Henske EP
Cancer research. 1998 ; 58 (21) : 4766-4770.
PMID 9809973
 
Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.
van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P
Human molecular genetics. 1998 ; 7 (6) : 1053-1057.
PMID 9580671
 
gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.
Ito N, Rubin GM
Cell. 1999 ; 96 (4) : 529-539.
PMID 10052455
 
Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice.
Kobayashi T, Minowa O, Kuno J, Mitani H, Hino O, Noda T
Cancer research. 1999 ; 59 (6) : 1206-1211.
PMID 10096549
 
Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.
Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ
The Journal of clinical investigation. 1999 ; 104 (6) : 687-695.
PMID 10491404
 
Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.
Carsillo T, Astrinidis A, Henske EP
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (11) : 6085-6090.
PMID 10823953
 
A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice.
Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T, Hino O
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (15) : 8762-8767.
PMID 11438694
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written11-2001Aristotelis Astrinidis and Elizabeth Petri Henske
Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia PA 19111, USA

Citation

This paper should be referenced as such :
Astrinidis, A ; Petri, Henske E
TSC2 (tuberous sclerosis 2)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(1):27-28.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/TSC2ID184.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 30 16:41:52 CEST 2014

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