The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a
protein that in humans is encoded by the NR0B2gene.[5] SHP is a member of the
nuclear receptor family of
intracellulartranscription factors.[6] SHP is unusual for a nuclear receptor in that it lacks a
DNA binding domain. Therefore, it is technically 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.
Function
The principal role of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer.[7] The protein has also been identified as a mediating factor in the metabolic circadian clock.[8] Research shows that it interacts 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.[5]
Structure and ligands
A crystal structure of the LBD-only SHP, generated by co-crystallisation with EID1, has been obtained. Instead binding to the usual AF-2 site, EID1 fills in the place of what is usually helix α1 of an LBD and makes SHP more soluble. The overall structure resembles the apo (ligandless) form of other LBDs. Some synthetic
retinoid ligands can bind to SHP's LBD and promote its interaction with LXXLL-containing corepressors using the AF-2 site.[9]
Interactions
Large and medium scale Y2H experiments as well as text mining of the NR literature have highlighted the important role of SHP in the Nuclear Receptor dimerization network and its relatively highly connected status, compared to other NRs.[10]
Small heterodimer partner has been shown to
interact with:
^Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry. 40 (50): 15369–77.
doi:
10.1021/bi011384o.
PMID11735420.
Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry. 40 (50): 15369–77.
doi:
10.1021/bi011384o.
PMID11735420.
Ogata M, Awaji T, Iwasaki N, Miyazaki S, Bell GI, Iwamoto Y (March 2002). "Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells". Biochemical and Biophysical Research Communications. 292 (1): 8–12.
doi:
10.1006/bbrc.2002.6593.
PMID11890664.
The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a
protein that in humans is encoded by the NR0B2gene.[5] SHP is a member of the
nuclear receptor family of
intracellulartranscription factors.[6] SHP is unusual for a nuclear receptor in that it lacks a
DNA binding domain. Therefore, it is technically 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.
Function
The principal role of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer.[7] The protein has also been identified as a mediating factor in the metabolic circadian clock.[8] Research shows that it interacts 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.[5]
Structure and ligands
A crystal structure of the LBD-only SHP, generated by co-crystallisation with EID1, has been obtained. Instead binding to the usual AF-2 site, EID1 fills in the place of what is usually helix α1 of an LBD and makes SHP more soluble. The overall structure resembles the apo (ligandless) form of other LBDs. Some synthetic
retinoid ligands can bind to SHP's LBD and promote its interaction with LXXLL-containing corepressors using the AF-2 site.[9]
Interactions
Large and medium scale Y2H experiments as well as text mining of the NR literature have highlighted the important role of SHP in the Nuclear Receptor dimerization network and its relatively highly connected status, compared to other NRs.[10]
Small heterodimer partner has been shown to
interact with:
^Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry. 40 (50): 15369–77.
doi:
10.1021/bi011384o.
PMID11735420.
Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry. 40 (50): 15369–77.
doi:
10.1021/bi011384o.
PMID11735420.
Ogata M, Awaji T, Iwasaki N, Miyazaki S, Bell GI, Iwamoto Y (March 2002). "Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells". Biochemical and Biophysical Research Communications. 292 (1): 8–12.
doi:
10.1006/bbrc.2002.6593.
PMID11890664.