TSC2

Identity

HGNC	TSC2
Location	16p13.3

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

External links

	Nomenclature
HGNC	TSC2   12363
Entrez_Gene	TSC2  7249  tuberous sclerosis 2
	Cards
Atlas	TSC2ID184
GeneCards	TSC2
Ensembl	TSC2 [Search_View]   ENSG00000103197 [Gene_View]
Genatlas	TSC2
GeneLynx	TSC2
eGenome	TSC2
euGene	7249
	Genomic and cartography
GoldenPath	TSC2  -  16p13.3   chr16:2037991-2078714 +  16p13.3   [Description]    (hg18-Mar_2006)
Ensembl	TSC2 - 16p13.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	TSC2
	Gene and transcription
Genbank	AB210000 [ ENTREZ ]
Genbank	AK022401 [ ENTREZ ]
Genbank	AK094152 [ ENTREZ ]
Genbank	AK125096 [ ENTREZ ]
Genbank	AK295728 [ ENTREZ ]
RefSeq	NM_000548 [ SRS ]    NM_000548 [ ENTREZ ]
RefSeq	NM_001077183 [ SRS ]    NM_001077183 [ ENTREZ ]
RefSeq	NM_001114382 [ SRS ]    NM_001114382 [ ENTREZ ]
RefSeq	AC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
RefSeq	AC_000148 [ SRS ]    AC_000148 [ ENTREZ ]
RefSeq	NC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
RefSeq	NG_005895 [ SRS ]    NG_005895 [ ENTREZ ]
RefSeq	NT_037887 [ SRS ]    NT_037887 [ ENTREZ ]
RefSeq	NW_001838339 [ SRS ]    NW_001838339 [ ENTREZ ]
RefSeq	NW_926018 [ SRS ]    NW_926018 [ ENTREZ ]
AceView	TSC2 AceView - NCBI
Unigene	Hs.90303 [ SRS ]    Hs.90303 [ NCBI ]     HS90303 [ spliceNest ]
Fast-db	1851 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P49815 [ SRS]    P49815 [ EXPASY ]     P49815 [ INTERPRO ]     P49815 [ UNIPROT ]
Prosite	PS50085 RAPGAP [ SRS ]    PS50085 RAPGAP [ Expasy ]
Interpro	IPR000331 Rap_GAP [ SRS ]    IPR000331 Rap_GAP [ EBI ]
Interpro	IPR003913 Tuberin [ SRS ]    IPR003913 Tuberin [ EBI ]
CluSTr	P49815
Pfam	PF02145 Rap_GAP [ SRS ]    PF02145 Rap_GAP [ Sanger ]    pfam02145 [ NCBI-CDD ]
Pfam	PF03542 Tuberin [ SRS ]    PF03542 Tuberin [ Sanger ]    pfam03542 [ NCBI-CDD ]
Blocks	P49815
HPRD	01850
	Protein Interaction databases
DIP	P49815
IntAct	P49815
	Polymorphism : SNP, mutations, diseases
OMIM	191092;191100;606690    [ map ]
GENECLINICS	191092;191100;606690
SNP	TSC2 [dbSNP-NCBI]
SNP	NM_000548 [SNP-NCI]
SNP	NM_001077183 [SNP-NCI]
SNP	NM_001114382 [SNP-NCI]
SNP	TSC2 [GeneSNPs - Utah]  TSC2] [HGBASE - SRS]
HAPMAP	TSC2 [HAPMAP]
COSMIC	TSC2 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	TSC2
	General knowledge
Family Browser	TSC2 [UCSC Family Browser]
SOURCE	NM_000548
SOURCE	NM_001077183
SOURCE	NM_001114382
SMD	Hs.90303
SAGE	Hs.90303
GO	neural tube closure [Amigo]  neural tube closure
GO	GTPase activator activity [Amigo]  GTPase activator activity
GO	GTPase activator activity [Amigo]  GTPase activator activity
GO	binding [Amigo]  binding
GO	protein binding [Amigo]  protein binding
GO	intracellular [Amigo]  intracellular
GO	membrane fraction [Amigo]  membrane fraction
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytoplasm [Amigo]  cytoplasm
GO	Golgi apparatus [Amigo]  Golgi apparatus
GO	Golgi apparatus [Amigo]  Golgi apparatus
GO	cytosol [Amigo]  cytosol
GO	cytosol [Amigo]  cytosol
GO	negative regulation of protein kinase activity [Amigo]  negative regulation of protein kinase activity
GO	protein import into nucleus [Amigo]  protein import into nucleus
GO	heart development [Amigo]  heart development
GO	protein localization [Amigo]  protein localization
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	negative regulation of phosphoinositide 3-kinase cascade [Amigo]  negative regulation of phosphoinositide 3-kinase cascade
GO	membrane [Amigo]  membrane
GO	regulation of endocytosis [Amigo]  regulation of endocytosis
GO	TSC1-TSC2 complex [Amigo]  TSC1-TSC2 complex
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	positive regulation of GTPase activity [Amigo]  positive regulation of GTPase activity
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	regulation of insulin receptor signaling pathway [Amigo]  regulation of insulin receptor signaling pathway
GO	insulin-like growth factor receptor signaling pathway [Amigo]  insulin-like growth factor receptor signaling pathway
GO	perinuclear region of cytoplasm [Amigo]  perinuclear region of cytoplasm
GO	positive chemotaxis [Amigo]  positive chemotaxis
GO	regulation of small GTPase mediated signal transduction [Amigo]  regulation of small GTPase mediated signal transduction
GO	negative regulation of protein kinase B signaling cascade [Amigo]  negative regulation of protein kinase B signaling cascade
BIOCARTA	mTOR Signaling Pathway    [Genes]
BIOCARTA	Control of Gene Expression by Vitamin D Receptor    [Genes]
KEGG	mTOR signaling pathway
KEGG	Insulin signaling pathway
PubGene	TSC2
TreeFam	TSC2
CTD	7249 [Comparative ToxicoGenomics Database]
	Other databases
Other database	http://zk.bwh.harvard.edu/ts/TSC2-19.htm
	Probes
Probe	TSC2 Related clones (RZPD - Berlin)
	PubMed
PubMed	147 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	11-2001	Aristotelis 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. Atlas Genet Cytogenet Oncol Haematol. November 2001 . URL : http://AtlasGeneticsOncology.org/Genes/TSC2ID184.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:18:20 2008