Domain

FKBP12-rapamycin binding domain (IPR009076)

Short name: FRB_dom

Domain relationships

None.

Description

The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the Tor proteins.

This entry represents the FRB domain [PMID: 8662507, PMID: 26700129]. Proteins containing this domain include Tor proteins which are serine/threonine kinases conserved from fungi to humans. While higher eukaryotes such as humans possess a single Tor protein, yeasts contain two (Tor1 and Tor2) [PMID: 26028537].

In budding yeast, the Tor2 protein exists in two distinct multi-component complexes, TORC1 and TORC2. TORC1 regulates cell growth by regulating many growth-related processes and is rapamycin sensitive, while TROC2 regulates the cell cytoskeleton and is rapamycin insensitive. Budding yeast TORC1 consists of either Tor1 or Tor2 in complex with Kog1, Lst8 and Tco89, while TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 [PMID: 26700129, PMID: 15689497]. In both yeast and mammals, FKBP12-rapamycin binds to Tor (Tor1, Tor2, or mTOR) in TORC1, but not to Tor (Tor2 or mTOR) in TORC2. It has been suggested that the architecture of TORC2 or its unique composition might be responsible for the observed rapamycin resistance [PMID: 26028537].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0044877 macromolecular complex binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
SUPERFAMILY
Pfam
GENE3D