The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several

nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...

-interacting domains. In addition, NCOR2 appears to recruit

histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...

s to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down

regulation Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. For ...

of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T₃ receptor-associating cofactor 1 (TRAC-1).

Function

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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

nuclear receptor-interacting domains. NCOR2/SMRT serves as a repressive coregulatory factor (

corepressor 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, b ...

) for multiple

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of

s to the DNA promoters bound by its interacting transcription factors.

Family

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 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. NCOR1 is a transcriptional coregulatory protein which c ...

.UniPro
Nuclear receptor corepressors family
Page accessed June 26, 2016

Discovery

SMRT was initially cloned and characterized in the laboratory of Dr.

Ronald M. Evans Ronald Mark Evans (born April 17, 1949 in Los Angeles, California) is an American Biologist, Professor and Head of the Salk’s Gene Expression Laboratory, and the March of Dimes Chair in Molecular and Developmental Biology at the Salk Institute fo ...

at the Salk Institute for Biological Studies. In another early investigation into this molecule, similar findings were reported in a variant referred to as TRAC-1.

Interactions

Nuclear receptor co-repressor 2 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: * AR, * BCL6, *

C-Fos Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...

, *

C-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...

, *

HDAC1 Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. T ...

, *

HDAC3 Histone deacetylase 3 is an enzyme encoded by the ''HDAC3'' gene in both humans and mice. Function Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein comp ...

, *

HDAC4 Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the ''HDAC4'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation ...

, *

HDAC5 Histone deacetylase 5 is an enzyme that in humans is encoded by the ''HDAC5'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alte ...

, *

HDAC10 Histone deacetylase 10 is an enzyme that in humans is encoded by the ''HDAC10'' gene. Acetylation of histone core particles modulates chromatin structure and gene expression. The opposing enzymatic activities of histone acetyltransferases and hist ...

, *

MeCP2 ''MECP2'' (methyl CpG binding protein 2) is a gene that encodes the protein MECP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in ...

, *

NR4A1 The nuclear receptor 4A1 (NR4A1 for "nuclear receptor subfamily 4 group A member 1") also known as Nur77, TR3, and NGFI-B is a protein that in humans is encoded by the ''NR4A1'' gene. Nuclear receptor 4A1 (NR4A1) is a member of the ''NR4A'' nucle ...

, *

POU2F1 POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene. Interactions POU2F1 has been shown to interact with: * EPRS, * Glucocorticoid receptor, * Glyceraldehyde 3-phosphate dehydrogenase, ...

, * PPARD, * PGR, * PML *

RBPJ Recombination signal binding protein for immunoglobulin kappa J region is a protein that in humans is encoded by the ''RBPJ'' gene. RBPJ also known as CBF1, is the human homolog for the Drosophila gene Suppressor of Hairless. Its promoter region ...

, *

RELA Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene. RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tran ...

, *

RUNX1T1 Protein CBFA2T1 is a protein that in humans is encoded by the ''RUNX1T1'' gene. Function The protein encoded by this gene is a putative zinc finger transcription factor and oncoprotein. In acute myeloid leukemia, especially in the M2 subtype, ...

, *

RARA Rara is a form of festival music that originated in Haiti that is used for street processions, typically during Easter Week. The music centers on a set of cylindrical bamboo trumpets called vaksin, but also features drums, maracas, güiras or g ...

, *

SIN3A Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the ''SIN3A'' gene. Function The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which a ...

, *

SNW1 SNW domain-containing protein 1 is a protein that in humans is encoded by the ''SNW1'' gene. Function This gene, a member of the SNW gene family, encodes a coactivator that enhances transcription from some Pol II promoters. This coactivator can ...

, *

SPEN Msx2-interacting protein is a protein that in humans is encoded by the ''SPEN'' gene. This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other rep ...

, * SRF, *

TBL1X Transducin (beta)-like 1X-linked, also known as TBL1X, is a protein which in humans is encoded by the ''TBL1X'' gene. Function The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. ...

, *

THRB Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the ''THRB'' gene. Function The protein encoded by this gene is a nuclear ...

, * VDR, and * ZBTB16.

References

External links