Free for academic non-profit institutions. Other users need a Commercial license

Aliases for TSC2 Gene

Aliases for TSC2 Gene

  • Tuberous Sclerosis 2 2 3
  • Tuberous Sclerosis 2 Protein 3 4
  • TSC4 3 4
  • LAM 3 6
  • Protein Phosphatase 1, Regulatory Subunit 160 3
  • Regulatory Subunit 160 2
  • Protein Phosphatase 1 2
  • PPP1R160 3
  • Tuberin 3

External Ids for TSC2 Gene

Previous HGNC Symbols for TSC2 Gene

  • TSC4

Previous GeneCards Identifiers for TSC2 Gene

  • GC16P002115
  • GC16P002038
  • GC16P002037
  • GC16P002097

Summaries for TSC2 Gene

Entrez Gene Summary for TSC2 Gene

  • Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for TSC2 Gene

TSC2 (Tuberous Sclerosis 2) is a Protein Coding gene. Diseases associated with TSC2 include lymphangioleiomyomatosis and tuberous sclerosis. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include protein homodimerization activity and GTPase activator activity. An important paralog of this gene is RALGAPA1.

UniProtKB/Swiss-Prot for TSC2 Gene

  • In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in TSC2 lead to constitutive activation of RAP1A in tumors.

Gene Wiki entry for TSC2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TSC2 Gene

Genomics for TSC2 Gene

Regulatory Elements for TSC2 Gene

Transcription factor binding sites by QIAGEN in the TSC2 gene promoter:

Genomic Location for TSC2 Gene

Start:
2,047,465 bp from pter
End:
2,088,720 bp from pter
Size:
41,256 bases
Orientation:
Plus strand

Genomic View for TSC2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TSC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TSC2 Gene

Proteins for TSC2 Gene

  • Protein details for TSC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49815-TSC2_HUMAN
    Recommended name:
    Tuberin
    Protein Accession:
    P49815
    Secondary Accessions:
    • A7E2E2
    • B4DIL8
    • B4DIQ7
    • B4DRN2
    • B7Z2B8
    • C9J378
    • O75275
    • Q4LE71
    • Q8TAZ1

    Protein attributes for TSC2 Gene

    Size:
    1807 amino acids
    Molecular mass:
    200608 Da
    Quaternary structure:
    • Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1. May also interact with the adapter molecule RABEP1. The final complex contains TSC2 and RABEP1 linked to RAB5 (Probable). Interacts with HSPA1 and HSPA8. Interacts with DAPK1 and FBXW5. Interacts with NAA10 (via C-terminal domain). Interacts with human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1.
    SequenceCaution:
    • Sequence=BAE06082.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for TSC2 Gene

neXtProt entry for TSC2 Gene

Proteomics data for TSC2 Gene at MOPED

Post-translational modifications for TSC2 Gene

  • Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.
  • Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 inependently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination.
  • Ubiquitination at Lys34, Lys72, Lys438, Lys634, Lys658, Lys914, Lys930, Lys1251, Lys1701, and Lys1739
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TSC2 Gene

Domains for TSC2 Gene

Protein Domains for TSC2 Gene

Suggested Antigen Peptide Sequences for TSC2 Gene

Graphical View of Domain Structure for InterPro Entry

P49815

UniProtKB/Swiss-Prot:

TSC2_HUMAN :
  • P49815
Domain:
  • Contains 1 Rap-GAP domain.
genes like me logo Genes that share domains with TSC2: view

No data available for Gene Families for TSC2 Gene

Function for TSC2 Gene

Molecular function for TSC2 Gene

UniProtKB/Swiss-Prot Function: In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in TSC2 lead to constitutive activation of RAP1A in tumors.

Gene Ontology (GO) - Molecular Function for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IDA 9045618
GO:0005488 binding --
GO:0005515 protein binding IPI 10585443
GO:0019902 phosphatase binding IDA 19389623
GO:0042803 protein homodimerization activity IPI 10585443
genes like me logo Genes that share ontologies with TSC2: view
genes like me logo Genes that share phenotypes with TSC2: view

Animal Models for TSC2 Gene

MGI Knock Outs for TSC2:

miRNA for TSC2 Gene

miRTarBase miRNAs that target TSC2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for TSC2 Gene

Localization for TSC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TSC2 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TSC2 Gene COMPARTMENTS Subcellular localization image for TSC2 gene
Compartment Confidence
cytosol 5
golgi apparatus 5
nucleus 5
plasma membrane 3
cytoskeleton 2
endosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 NOT nucleus IDA 16636147
GO:0005737 colocalizes_with cytoplasm IDA 17114346
GO:0005794 NOT Golgi apparatus IDA 10585443
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
genes like me logo Genes that share ontologies with TSC2: view

Pathways for TSC2 Gene

SuperPathways for TSC2 Gene

Superpath Contained pathways
1 Insulin receptor signalling cascade
2 PI-3K cascade
3 Signaling by FGFR
4 Translation Insulin regulation of translation
5 Downstream Signaling Events Of B Cell Receptor (BCR)
genes like me logo Genes that share pathways with TSC2: view

Gene Ontology (GO) - Biological Process for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0001843 neural tube closure ISS --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0006469 negative regulation of protein kinase activity ISS --
GO:0006606 protein import into nucleus ISS --
genes like me logo Genes that share ontologies with TSC2: view

Compounds for TSC2 Gene

(25) Novoseek inferred chemical compound relationships for TSC2 Gene

Compound -log(P) Hits PubMed IDs
rapamycin 89.6 85
wortmannin 50.8 5
phosphatidylinositol 42.4 9
phosphoinositide 37.8 6
ly294002 33 3

(1) PharmGKB related drug/compound annotations for TSC2 Gene

Drug/compound Annotation
everolimus
genes like me logo Genes that share compounds with TSC2: view

Transcripts for TSC2 Gene

Unigene Clusters for TSC2 Gene

Tuberous sclerosis 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TSC2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b · 17c · 17d ^ 18 ^ 19 ^
SP1: - - - - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7: -
SP8:
SP9:
SP10:
SP11:
SP12: -
SP13:
SP14:
SP15: - -
SP16:
SP17: -
SP18:

ExUns: 20a · 20b ^ 21 ^ 22a · 22b ^ 23a · 23b ^ 24 ^ 25a · 25b · 25c · 25d ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29a · 29b · 29c ^ 30a · 30b · 30c ^ 31 ^ 32 ^ 33a ·
SP1: - - - -
SP2:
SP3: - - - -
SP4: -
SP5: - - - -
SP6:
SP7:
SP8: - -
SP9: - - -
SP10:
SP11:
SP12:
SP13: -
SP14:
SP15:
SP16:
SP17:
SP18:

ExUns: 33b ^ 34a · 34b ^ 35a · 35b ^ 36 ^ 37a · 37b · 37c ^ 38 ^ 39 ^ 40 ^ 41 ^ 42 ^ 43 ^ 44 ^ 45a · 45b
SP1: - - - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10: - - -
SP11:
SP12:
SP13:
SP14:
SP15:
SP16: - -
SP17:
SP18:

Relevant External Links for TSC2 Gene

GeneLoc Exon Structure for
TSC2
ECgene alternative splicing isoforms for
TSC2

Expression for TSC2 Gene

mRNA expression in normal human tissues for TSC2 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for TSC2 Gene

SOURCE GeneReport for Unigene cluster for TSC2 Gene Hs.90303

mRNA Expression by UniProt/SwissProt for TSC2 Gene

P49815-TSC2_HUMAN
Tissue specificity: Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta
genes like me logo Genes that share expressions with TSC2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for TSC2 Gene

Orthologs for TSC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TSC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TSC2 35
  • 99.04 (n)
  • 99.11 (a)
TSC2 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TSC2 35
  • 87.47 (n)
  • 91.6 (a)
TSC2 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TSC2 35
  • 86.77 (n)
  • 91.64 (a)
TSC2 36
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tsc2 35
  • 84.86 (n)
  • 91.65 (a)
Tsc2 16
Tsc2 36
  • 91 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 88 (a)
OneToMany
-- 36
  • 87 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 91 (a)
OneToMany
-- 36
  • 82 (a)
OneToMany
-- 36
  • 82 (a)
OneToMany
-- 36
  • 64 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Tsc2 35
  • 85.16 (n)
  • 91.3 (a)
chicken
(Gallus gallus)
Aves TSC2 35
  • 74.88 (n)
  • 82.33 (a)
TSC2 36
  • 81 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TSC2 36
  • 81 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.7502 35
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.18146 35
tsc2 35
  • 68.09 (n)
  • 69.92 (a)
zebrafish
(Danio rerio)
Actinopterygii tsc2 35
  • 63.26 (n)
  • 60.21 (a)
tsc2 36
  • 57 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011123 35
  • 42.47 (n)
  • 26.09 (a)
fruit fly
(Drosophila melanogaster)
Insecta gig 35
  • 49.52 (n)
  • 37.89 (a)
gig 36
  • 31 (a)
OneToOne
gig 37
  • 31 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 35 (a)
OneToOne
Species with no ortholog for TSC2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TSC2 Gene

ENSEMBL:
Gene Tree for TSC2 (if available)
TreeFam:
Gene Tree for TSC2 (if available)

Paralogs for TSC2 Gene

Paralogs for TSC2 Gene

Selected SIMAP similar genes for TSC2 Gene using alignment to 9 proteins:

genes like me logo Genes that share paralogs with TSC2: view

Variants for TSC2 Gene

Sequence variations from dbSNP and Humsavar for TSC2 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs30259 -- 2,083,900(-) CCCAG(A/G)GTGCA intron-variant
rs30260 -- 2,081,173(-) GCCCC(A/C)ATGTT intron-variant
rs1051616 untested, - 2,053,396(+) AGCGG(A/C)CGCTG missense, reference
rs1051621 - 2,074,250(+) GCCAG(A/C)CAGTG missense, reference
rs1131825 untested, - 2,058,858(+) GTGTT(G/T)CCATC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for TSC2 Gene

Variant ID Type Subtype PubMed ID
esv2422427 CNV Duplication 17116639
dgv2540n71 CNV Loss 21882294
dgv2544n71 CNV Loss 21882294
dgv2545n71 CNV Loss 21882294
nsv905048 CNV Loss 21882294
dgv2546n71 CNV Loss 21882294
dgv2547n71 CNV Loss 21882294
dgv2548n71 CNV Gain 21882294
dgv2549n71 CNV Loss 21882294
dgv2550n71 CNV Loss 21882294
dgv2552n71 CNV Gain+Loss 21882294
nsv523037 CNV Loss 19592680
nsv471072 CNV Loss 18288195
dgv2555n71 CNV Gain+Loss 21882294
nsv905095 CNV Gain 21882294
nsv905101 CNV Loss 21882294
nsv905102 CNV Loss 21882294
dgv2556n71 CNV Loss 21882294
dgv2557n71 CNV Loss 21882294
nsv827504 CNV Loss 20364138
nsv457349 CNV Loss 19166990
dgv2558n71 CNV Loss 21882294
nsv905113 CNV Loss 21882294
dgv2559n71 CNV Loss 21882294
esv2750376 CNV Deletion 23290073
dgv2560n71 CNV Loss 21882294
dgv2561n71 CNV Loss 21882294
nsv471381 CNV Duplication 19718026
nsv482186 CNV Gain 20164927

Relevant External Links for TSC2 Gene

HapMap Linkage Disequilibrium report
TSC2
Human Gene Mutation Database (HGMD)
TSC2
Locus Specific Mutation Databases (LSDB)
TSC2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TSC2 Gene

Disorders for TSC2 Gene

(2) OMIM Diseases for TSC2 Gene (191092)

UniProtKB/Swiss-Prot

TSC2_HUMAN
  • Tuberous sclerosis 2 (TSC2) [MIM:613254]: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes. {ECO:0000269 PubMed:10069705, ECO:0000269 PubMed:10205261, ECO:0000269 PubMed:10533067, ECO:0000269 PubMed:10570911, ECO:0000269 PubMed:10607950, ECO:0000269 PubMed:10732801, ECO:0000269 PubMed:10735580, ECO:0000269 PubMed:15024740, ECO:0000269 PubMed:15595939, ECO:0000269 PubMed:8824881, ECO:0000269 PubMed:9302281, ECO:0000269 PubMed:9463313, ECO:0000269 PubMed:9829910}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex. {ECO:0000269 PubMed:10823953}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(73) Novoseek inferred disease relationships for TSC2 Gene

Disease -log(P) Hits PubMed IDs
tuberous sclerosis 98.5 163
lymphangioleiomyomatosis 92 24
hamartoma 90.5 63
angiomyolipoma 89 45
astrocytoma subependymal giant cell 87.4 13

Genatlas disease for TSC2 Gene

tuberous sclerosis 2,multisystem disorder characterized by the widespread development of hamartomatous growths noteworthy in eyes,heart,skin and brain,with seizures,behavioral disorder and a renal angiomyolipoma and lymphangiomatosis,with a high risk of mental retardation

Relevant External Links for TSC2

GeneTests
TSC2
GeneReviews
TSC2
Genetic Association Database (GAD)
TSC2
Human Genome Epidemiology (HuGE) Navigator
TSC2
genes like me logo Genes that share disorders with TSC2: view

Publications for TSC2 Gene

  1. Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients. (PMID: 8824881) Wilson P.J. … Haines J.L. (Hum. Mol. Genet. 1996) 3 4 23
  2. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. (PMID: 9302281) Maheshwar M.M. … Sampson J.R. (Hum. Mol. Genet. 1997) 3 4 23
  3. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. (PMID: 9580671) van Slegtenhorst M.A. … van der Sluijs P. (Hum. Mol. Genet. 1998) 3 4 23
  4. Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis. (PMID: 9829910) Beauchamp R.L. … Ramesh V. (Hum. Mutat. 1998) 3 4 23
  5. Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack of loss of heterozygosity in a lung cyst. (PMID: 10069705) Zhang H. … Ohno K. (Am. J. Med. Genet. 1999) 3 4 23

Products for TSC2 Gene

  • Addgene plasmids for TSC2

Sources for TSC2 Gene

Back to Top

Content