The nuclear receptor co-repressor 2 ( NCOR2 ) is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. [5] [6] NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) [5] or T3 receptor-associating cofactor 1 (TRAC-1). [6]
NCOR2/SMRT is a transcriptional coregulatory protein that contains several modulatory functional domains including multiple autonomous repression domains as well as two or three C-terminal nuclear receptor-interacting domains. [5] NCOR2/SMRT serves as a repressive coregulatory factor (corepressor) for multiple transcription factor pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors. [7]
It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 1. [8]
SMRT was initially cloned and characterized in the laboratory of Dr. Ronald M. Evans at the Salk Institute for Biological Studies. [5] In another early investigation into this molecule, similar findings were reported in a variant referred to as TRAC-1. [6]
Nuclear receptor co-repressor 2 has been shown to interact with:
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.
The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.
In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, but instead indirectly regulates gene expression by binding to repressors.
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.
Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.
Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.
Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.
Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.
C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2.
Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.
Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene.
Histone deacetylase 7 is an enzyme that in humans is encoded by the HDAC7 gene.
Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.
Paired amphipathic helix protein Sin3b is a protein that in humans is encoded by the SIN3B gene.
Transducin (beta)-like 1X-linked, also known as TBL1X, is a protein which in humans is encoded by the TBL1X gene.
Histone deacetylase complex subunit SAP18 is an enzyme that in humans is encoded by the SAP18 gene.
Nuclear receptor coregulators are a class of transcription coregulators that have been shown to be involved in any aspect of signaling by any member of the nuclear receptor superfamily. A comprehensive database of coregulators for nuclear receptors and other transcription factors was previously maintained at the Nuclear Receptor Signaling Atlas website which has since been replaced by the Signaling Pathways Project website.
The BTB/POZ domain is a common structural domain contained within some proteins. It is present near the N-terminus of a fraction of zinc finger proteins and in proteins that contain the Kelch motif and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerisation and in some instances heteromeric dimerisation. The structure of the dimerised PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. BTB/POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.
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