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The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. 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. Acts as a novel corepressor for basic helix-loop-helix transcription factor BETA2/NeuroD. At diagnosis, methylation of SHP1 occurred more frequently in acute myeloid leukaemia than acute lymphoblastic leukaemia. Frequent methylation of SHP1, but not SOCS1, may be important in the pathogenesis, but not prognosis, of acute leukaemias. Modulation of SHP expression and/or activity in adipose tissue may therefore have significant effects on aromatase expression and estrogen production in breast adipose tissue. NR0B2 is involved in the regulation of G6Pase, CYP7A1, and PEPCK gene expression via novel mechanism of inhibition of HNF3 activity and expand the role of NR0B2 as a coregulator of other family of transcription factors in addition to nuclear receptors. PGC-1alpha mediates the ligand-dependent activation of FXR and transcription of SHP gene. Results suggest that SHP mediates recruitment of mSin3A-Swi/Snf to the CYP7A1 promoter, resulting in chromatin remodeling and gene repression. SHP affects genes involved in diverse biological pathways, e.g., several key genes involved in consecutive steps of cholesterol degradation, bile acid conjugation, transport and lipogenic pathways. SHP has a role in modulating hepatic glucocorticoid action. SHP is able to interact with LXR and to modulate its transcriptional activity. SHP mutations found in obese Danish men. SHP-1 tyrosine phosphatase is regulated in human platelets by serine phosphorylation at its C terminus. Basic helix-loop-helix (bHLH) transcription factors, the E2A proteins (E47, E12 and E2/5), activated the human but not the mouse SHP promoter. C-Jun works to activate the expression of SHP genes associated with the cascade regulation of monocytic differentiation. Crystal structure at 1.9 A resoluation of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which contacts the AF-2 region of hLRH-1 using selective structural motifs. Orphan nuclear receptor small heterodimer partner promoter is regulated by sterol regulatory element binding protein-1. Orphan receptor small heterodimer partner expression is regulated by estrogen receptor alpha. Polymorphisms in the human SHP1 gene; found no rare SHP1 coding sequence variants that were exclusive to patients with lipodystrophy. Results suggest that bile acids negatively regulate the human angiotensinogen gene through the inhibitory effect of small heterodimer partner on hepatocyte nuclear factor-4. The relation between genetic variation in SHP and birth weight, adiposity, and insulin levels in three independent populations.
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