TSC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5EJC, 4Z6Y
Identifiers
Aliases	TSC1, LAM, TSC, tuberous sclerosis 1, TSC complex subunit 1
External IDs	OMIM: 605284 MGI: 1929183 HomoloGene: 314 GeneCards: TSC1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.13 Start 132,891,348 bp[1] End 132,946,874 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 A3 Start 28,531,240 bp[2] End 28,581,179 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in external globus pallidus Region I of hippocampus proper inferior olivary nucleus superior vestibular nucleus middle temporal gyrus sural nerve corpus callosum parietal lobe biceps brachii pons Top expressed in ventromedial nucleus lateral hypothalamus supraoptic nucleus paraventricular nucleus of hypothalamus substantia nigra mammillary body arcuate nucleus nucleus accumbens median eminence olfactory tubercle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function chaperone binding protein binding protein N-terminus binding Hsp70 protein binding ATPase inhibitor activity Hsp90 protein binding GTPase activating protein binding Cellular component cytoplasm cell cortex growth cone intracellular membrane-bounded organelle lamellipodium membrane actin filament TSC1-TSC2 complex cytoskeleton cytosol nucleus perinuclear region of cytoplasm lipid droplet plasma membrane cell projection protein-containing complex chaperone complex postsynaptic density Biological process rRNA export from nucleus regulation of cell cycle neural tube closure cerebral cortex development memory T cell differentiation regulation of protein kinase activity positive regulation of focal adhesion assembly myelination negative regulation of insulin receptor signaling pathway synapse organization regulation of translation hippocampus development regulation of phosphoprotein phosphatase activity cell-matrix adhesion potassium ion transport adaptive immune response protein heterooligomerization kidney development nervous system development cell projection organization activation of GTPase activity regulation of focal adhesion assembly glucose import regulation of cell-matrix adhesion negative regulation of cell size response to insulin cardiac muscle cell differentiation negative regulation of translation negative regulation of cell population proliferation cellular response to oxygen-glucose deprivation adult locomotory behavior negative regulation of TOR signaling regulation of neuron death negative regulation of macroautophagy negative regulation of neuron projection development positive regulation of macroautophagy negative regulation of GTPase activity regulation of stress fiber assembly positive regulation of stress fiber assembly negative regulation of oxidative stress-induced neuron death negative regulation of ATP-dependent activity protein stabilization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7248 64930 Ensembl ENSG00000165699 ENSMUSG00000026812 UniProt Q92574 Q9EP53 RefSeq (mRNA) NM_000368 NM_001008567 NM_001162426 NM_001162427 NM_001362177 NM_022887 NM_001289575 NM_001289576 RefSeq (protein) NP_000359 NP_001155898 NP_001155899 NP_001349106 NP_001276504 NP_001276505 NP_075025 Location (UCSC) Chr 9: 132.89 – 132.95 Mb Chr 2: 28.53 – 28.58 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the TSC1 gene.^[5]

Function

TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and decelerates its chaperone cycle. Tsc1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including Tsc2, therefore preventing their ubiquitination and degradation in the proteasome.^[6] TSC1, TSC2 and TBC1D7 is a multi-protein complex also known as the TSC complex. This complex negatively regulates mTORC1 signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase Rheb, an essential activator of mTORC1. The TSC complex has been implicated as a tumor suppressor.

Clinical significance

Defects in this gene can cause tuberous sclerosis, due to a functional impairment of the TSC complex. Defects in TSC1 may also be a cause of focal cortical dysplasia. TSC1 may be involved in protecting brain neurons in the CA3 region of the hippocampus from the effects of stroke.^[7]

Interactions

TSC1 has been shown to interact with:

• AKT1,^[8][9]
• HSP70^[6]
• HSP90^[6]
• NEFL,^[10]
• PLK1,^[11] and
• TSC2.^{[9][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]}

See also

• Tuberous sclerosis protein

References

Further reading

External links

• GeneReviews/NIH/NCBI/UW entry on Tuberous Sclerosis Complex or Bourneville Disease
• Overview of all the structural information available in the PDB for UniProt: Q92574 (Hamartin) at the PDBe-KB.