Small heterodimer partner

The small heterodimer partner (SHP) protein is a member of the nuclear receptor family of intracellular transcription factors and is encoded by the (nuclear receptor subfamily 0, group B, member 2) gene. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore technically it is neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

The main function of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer. The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function.