Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2 (TANC2)

Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2 (TANC2) is a large, multi-domain scaffold protein predominantly localized to the postsynaptic density of excitatory neurons[1][2][3][5][6]. It contains conserved domains (ankyrin repeats, tetratricopeptide repeats, and a coiled-coil region), as well as a predicted N-terminal ATPase domain unique to TANC2[3]. TANC2 organizes multi-protein complexes at glutamatergic synapses, facilitating the recruitment of dense core vesicles and modulating synaptic strength and plasticity[2][5][6]. It regulates dendritic spine development and morphology and acts as an adaptor protein inhibiting mTORC1/mTORC2 signaling, with a critical role in synaptic and neuronal development[1][6]. Mutations in TANC2 are strongly associated with a spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability, autism, language delay, and schizophrenia[1][3][5]. Amplification of TANC2 has also been observed as an oncogenic driver in breast cancer, promoting proliferation and survival[1]. The protein's therapeutic targeting potential is being investigated, but approved drugs are not available[6].

Other names

KIAA1148KIAA1636DKFZP564D166FLJ10215FLJ11824ROLSROLSArolsrolling pebbles homolog B (Drosophila)IDDALDS

Not drug-established; molecularly, modulation of mTORC1/mTORC2 signaling and synaptic function via protein-protein interactions Potential mechanism for future drugs: inhibition/restoration of TANC2-mediated signaling and scaffold assembly