Recombinant Human Hamartin (TSC1), Truncated

Uniprot Id

Q92574

Target Species

Human

Target Name

TSC1

Target Full Name

Hamartin

Target 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. Acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1. Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity. Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1.

Target Involvement

Tuberous sclerosis 1 (TSC1); Lymphangioleiomyomatosis (LAM); Focal cortical dysplasia 2 (FCORD2)

Target Subcellular Location

Cytoplasm. Membrane; Peripheral membrane protein.

Target Tissue Specificity

Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.

Target Research Area

Cancer

Target Synonyms

Hamartin; kiaa0243; LAM; TSC; Tsc1; Tsc1 gene; TSC1_HUMAN; Tuberous sclerosis 1; Tuberous sclerosis 1 protein; tumor suppressor

Target Background

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) signaling 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 and lymphangioleiomyomatosis.