TSC1
TSC1 (TSC complex subunit 1), also known as hamartin, KIAA0243, LAM and TSC, is a non-catalytic tumour suppressor protein. It partners with tuberin (TSC2) to restrain mTORC1 signalling and also acts as an HSP90 co-chaperone. Browse Assay Genie's current range of TSC1 research reagents below, or read on for the biology behind the target.
TSC1 is a non-catalytic component of the TSC-TBC complex, a multiprotein assembly that negatively regulates the canonical mTORC1 complex. mTORC1 is an evolutionarily conserved nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. The TSC-TBC complex acts as a GTPase-activating protein for the small GTPase RHEB, a direct activator of mTORC1 kinase activity. Without nutrients, the complex inhibits mTORC1 and so prevents phosphorylation of ribosomal protein S6 kinases (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). Nutrients inactivate the complex, which relieves this inhibition.
Within the complex, hamartin stabilises TSC2 and prevents TSC2 self-aggregation. It also acts as a co-chaperone for HSP90AA1, increasing ATP binding while inhibiting HSP90AA1 ATPase activity. It competes with the activating co-chaperone AHSA1 for HSP90AA1 binding, which provides a reciprocal regulatory mechanism for client chaperoning. Clients include kinases, TSC2 and the glucocorticoid receptor NR3C1. By recruiting TSC2 to HSP90AA1 and blocking its interaction with the ubiquitin ligase HERC1, TSC1 prevents TSC2 ubiquitination and proteasomal degradation. Through its control of mTORC1 signalling it is also involved in microtubule-mediated protein transport.
The TSC1 gene encodes the growth-inhibitory protein hamartin, which UniProt records in the lysosome membrane and cytosol. HGNC lists it in the armadillo-like helical domain containing group and the TSC complex group, with the previous name tuberous sclerosis 1. Mutations in the gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. Mouse and rat both carry a Tsc1 ortholog.
TSC1 is part of the complex that inhibits mTORC1 in the absence of nutrients, making it central to studies of anabolic growth control.
Hamartin is a growth-inhibitory tumour suppressor, and its gene is linked to tuberous sclerosis and lymphangioleiomyomatosis.
As an HSP90 co-chaperone, TSC1 stabilises TSC2 and other clients by preventing their ubiquitination and proteasomal degradation.
Through mTORC1 regulation, TSC1 contributes to nutrient-responsive signalling and microtubule-mediated protein transport.
TSC1 is a non-catalytic subunit of the TSC-TBC complex, which acts as a GTPase-activating protein for RHEB and so inhibits mTORC1. It stabilises TSC2, prevents TSC2 self-aggregation and also works as an HSP90AA1 co-chaperone. It acts as a tumour suppressor.
TSC1 is the HGNC symbol for TSC complex subunit 1. The protein is called hamartin, and aliases include KIAA0243, LAM and TSC. The previous HGNC name was tuberous sclerosis 1. Its partner TSC2 is known as tuberin.
Mutations in the TSC1 gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. Mouse and rat each have a Tsc1 ortholog, so rodent models are used to study it. Check the datasheet of any product for its validated reactivity.
TSC2, the partner of TSC1 in the TSC complex, and TSC22 domain family proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q92574; product specifications from Assay Genie datasheets.