Description: Homo sapiens tuberous sclerosis 1 (TSC1), transcript variant 1, mRNA. RefSeq Summary (NM_000368): This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signalling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including Tsc2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis. [provided by RefSeq, Apr 2018]. Transcript (Including UTRs) Position: hg19 chr9:135,766,735-135,820,020 Size: 53,286 Total Exon Count: 23 Strand: - Coding Region Position: hg19 chr9:135,771,622-135,804,259 Size: 32,638 Coding Exon Count: 21
ID:TSC1_HUMAN DESCRIPTION: RecName: Full=Hamartin; AltName: Full=Tuberous sclerosis 1 protein; FUNCTION: In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. SUBUNIT: Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with FBXW5 and TBC1D7. INTERACTION: O14920:IKBKB; NbExp=3; IntAct=EBI-1047085, EBI-81266; Q16539:MAPK14; NbExp=2; IntAct=EBI-1047085, EBI-73946; Q00994:NGFRAP1; NbExp=5; IntAct=EBI-1047085, EBI-741753; P49815:TSC2; NbExp=7; IntAct=EBI-1047085, EBI-396587; SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes. TISSUE SPECIFICITY: Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells. DOMAIN: The C-terminal putative coiled-coil domain is necessary for interaction with TSC2. PTM: Phosphorylation at Ser-505 does not affect interaction with TSC2. Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Defects in TSC1 are the cause of tuberous sclerosis type 1 (TSC1) [MIM:191100]. It is an autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. TS1C 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 symptoms can range from benign hypopigmented macules of the skin to profound mental retardation with intractable seizures to premature death from a variety of disease-associated causes. DISEASE: Defects in TSC1 may be a cause of focal cortical dysplasia of Taylor balloon cell type (FCDBC) [MIM:607341]. FCDBC is a subtype of cortical displasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TSC1ID183.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TSC1"; WEB RESOURCE: Name=Tuberous sclerosis database Tuberous sclerosis 1 (TSC1); Note=Leiden Open Variation Database (LOVD); URL="http://www.LOVD.nl/TSC1";
To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): TSC1 CDC HuGE Published Literature: TSC1 Positive Disease Associations: Hip
, psoriasis Related Studies:
Hip Douglas P Kiel et al. BMC medical genetics 2007, Genome-wide association with bone mass and geometry in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903296]
The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.
Hip Douglas P Kiel et al. BMC medical genetics 2007, Genome-wide association with bone mass and geometry in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903296]
The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.
psoriasis Nair ,et al. 2009, Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways, Nature genetics 2009 41- 2 : 199-204.
[PubMed 19169254]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92574
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.