SESN2
SESN2 (sestrin 2, also known as SES2, HI95 and SEST2) is a stress-inducible member of the sestrin family that acts as an intracellular leucine sensor. It negatively regulates mTORC1 signalling through the GATOR complex and contributes to protection against oxidative and genotoxic stress. Browse Assay Genie's current range of SESN2 research reagents below, or read on for the biology behind the target.
SESN2 functions as an intracellular leucine sensor that negatively regulates the mTORC1 signalling pathway through the GATOR complex. When leucine is absent, SESN2 binds the GATOR subcomplex GATOR2 and prevents mTORC1 signalling. Binding of leucine to SESN2 disrupts this interaction with GATOR2, which activates TORC1 signalling. This makes the protein a direct link between amino acid availability and growth control.
SESN2 is also a stress-inducible metabolic regulator with roles in protection against oxidative and genotoxic stresses. It may negatively regulate protein translation in response to endoplasmic reticulum stress via mTORC1, and may mediate TP53 inhibition of TORC1 signalling after genotoxic stress. It may also positively regulate transcription by NFE2L2 of oxidative stress response genes by facilitating SQSTM1-mediated autophagic degradation of KEAP1. In addition, the alkylhydroperoxide reductase activity attributed to its N-terminal domain may help prevent accumulation of reactive oxygen species (ROS). An earlier report that SESN2 resists oxidative stress by reducing PRDX1 could not be confirmed.
The SESN2 gene encodes a member of the sestrin family of PA26-related proteins, and the protein is classed as an enzyme (EC 1.11.1.-) that localises to the cytoplasm. NCBI describes it as possibly involved in regulating cell growth and survival and in cellular responses to different stress conditions. The mouse ortholog is Sesn2. Other family members include SESN1 and SESN3.
SESN2 senses leucine and signals through GATOR2 to control mTORC1, making it a central protein for studying amino acid regulation of growth signalling.
SESN2 helps protect against oxidative stress, possibly through NFE2L2 signalling, KEAP1 degradation and limiting reactive oxygen species.
SESN2 may mediate TP53 inhibition of TORC1 signalling upon genotoxic stress, linking DNA damage responses to growth control.
SESN2 may negatively regulate protein translation via mTORC1 during endoplasmic reticulum stress, relevant to studies of stress-adaptive protein synthesis.
SESN2 is an intracellular leucine sensor that negatively regulates mTORC1 signalling through the GATOR complex. Without leucine it binds GATOR2 and prevents mTORC1 signalling; leucine binding releases this interaction. It also contributes to protection against oxidative and genotoxic stresses.
The HGNC name is sestrin 2, and the UniProt protein name is Sestrin-2. Aliases and previous symbols include SES2, DKFZp761M0212, HI95 and SEST2. SESN2 belongs to the sestrin family, which also includes SESN1 and SESN3.
The data list Sesn2 as the mouse ortholog of human SESN2, supporting rodent-based study of its function. No rat ortholog is given in the supplied data. Check the datasheet of any product for its validated reactivity.
Other sestrin family members with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P58004; product specifications from Assay Genie datasheets.