The nuclear receptor co-repressor 2 is a transcriptional coregulatory

Transcription coregulator

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...

 protein that contains several nuclear receptor

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

-interacting domains. In addition, NCOR2 appears to recruit histone deacetylase

Histone deacetylase

Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...

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

Regulation of gene expression

Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...

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

Corepressor (genetics)

In molecular genetics, a corepressor is a substance that inhibits the expression of genes. A corepressor downregulates the expression of genes not through direct interaction with a gene promoter , but rather indirectly through interaction with repressor proteins that in turn bind to the...

) for multiple transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

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

Histone deacetylase

Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...

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

Discovery

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

Ronald M. Evans

Ronald M. Evans is an American professor and biologist who works at the Salk Institute for Biological Studies in La Jolla, California. He received his BS and PhD degrees from UCLA, followed by a postdoctoral training in Rockefeller University...

 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

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Thyroid hormone receptor beta

Thyroid hormone receptor beta

Thyroid hormone receptor beta also known as nuclear receptor subfamily 1, group A, member 2 , is a nuclear receptor protein that in humans is encoded by the THRB gene.- Function :...

, Retinoic acid receptor alpha

Retinoic acid receptor alpha

Retinoic acid receptor alpha , also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.- Function :...

, HDAC1

HDAC1

Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...

, Nerve Growth factor IB

Nerve Growth factor IB

The nerve Growth factor IB also known as Nur77 or NR4A1 is a protein that in humans is encoded by the NR4A1 gene....

, Zinc finger and BTB domain-containing protein 16

Zinc finger and BTB domain-containing protein 16

Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.-Function:This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the...

, SIN3A

SIN3A

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.-Interactions:SIN3A has been shown to interact with HDAC9, OGT, RBBP7, RBBP4, Host cell factor C1, MXD1, IKZF1, Nuclear receptor co-repressor 2, SAP130, KLF11, Methyl-CpG-binding domain protein 2, HDAC1,...

, BCL6

BCL6

B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain...

, SNW1

SNW1

SNW domain-containing protein 1 is a protein that in humans is encoded by the SNW1 gene.-Interactions:SNW1 has been shown to interact with Histone deacetylase 2, SKI protein, Retinoblastoma protein, PABPN1, CIR, RBPJ, Nuclear receptor coactivator 1, Nuclear receptor co-repressor 2, Calcitriol...

, Androgen receptor

Androgen receptor

The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...

, Peroxisome proliferator-activated receptor delta

Peroxisome proliferator-activated receptor delta

Peroxisome proliferator-activated receptor beta or delta , also known as NR1C2 is a nuclear receptor that in humans is encoded by the PPARD gene....

, C-Fos

C-Fos

In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...

, POU2F1

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 SNAPC4, Ku80, Glucocorticoid receptor, Sp1 transcription factor, NPAT, POU2AF1, Host cell factor C1, TATA binding protein, RELA, Nuclear...

, Histone deacetylase 5

Histone deacetylase 5

Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.-Interactions:Histone deacetylase 5 has been shown to interact with Zinc finger and BTB domain-containing protein 16, BCL6, CBX5, YWHAQ, Myocyte-specific enhancer factor 2A, Nuclear receptor co-repressor 1, IKZF1,...

, HDAC10

HDAC10

Histone deacetylase 10 is an enzyme that in humans is encoded by the HDAC10 gene.-Interactions:HDAC10 has been shown to interact with Histone deacetylase 2 and Nuclear receptor co-repressor 2....

, RELA

RELA

Transcription factor p65 is a protein that in humans is encoded by the RELA gene.-Interactions:RELA has been shown to interact with NFKBIB, ETHE1, NFKBIE, RFC1, TRIB3, CREB binding protein, Neutrophil cytosolic factor 1, Glucocorticoid receptor, MTPN, BRCA1, C-Fos, POU2F1, BTRC, TATA-binding...

, RBPJ

RBPJ

Recombining binding protein suppressor of hairless is a protein that in humans is encoded by the RBPJ gene.RBPJ, also named as CBF1, is a human homolog for the Drosophila gene Suppressor of Hairless...

, TBL1X

TBL1X

Transducin -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. The WD40 group is a large family of proteins, which appear to...

, RUNX1T1

RUNX1T1

Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.-Interactions:RUNX1T1 has been shown to interact with CBFA2T2, Zinc finger and BTB domain-containing protein 16, Nuclear receptor co-repressor 1, Nuclear receptor co-repressor 2, CBFA2T3, GFI1, Calcitriol receptor and...

, HDAC4

HDAC4

Histone deacetylase 4, also known as HDAC4, is a protein which 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/deacetylation alters chromosome structure and affects...

, Progesterone receptor

Progesterone receptor

The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...

, HDAC3

HDAC3

Histone deacetylase 3 is an enzyme that in humans is encoded by the HDAC3 gene.-Interactions:HDAC3 has been shown to interact with HDAC9, HDAC7A, Retinoblastoma protein, RBBP4, Testicular receptor 2, MAP3K7IP2, Peroxisome proliferator-activated receptor delta, GTF2I, Histone deacetylase 5, RELA,...

, SPEN

SPEN

Msx2-interacting protein is a protein that in humans is encoded by the SPEN gene.-Interactions:SPEN has been shown to interact with HDAC1, SRA1 and Nuclear receptor co-repressor 2.-Further reading:...

, Serum response factor

Serum response factor

Serum response factor , also known as SRF, is a transcription factor.It is a member of the MADS box superfamily of transcription factors. This protein binds to the serum response element in the promoter region of target genes...

, C-jun

C-jun

c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...

, Calcitriol receptor

Calcitriol receptor

The calcitriol receptor, also known as the vitamin D receptor and also known as NR1I1 , is a member of the nuclear receptor family of transcription factors...

 and Promyelocytic leukemia protein

Promyelocytic leukemia protein

Probable transcription factor PML is a tumor suppressor protein that in humans is encoded by the PML gene.-Interactions:Promyelocytic leukemia protein has been shown to interact with Retinoic acid receptor alpha, HDAC1, Nerve Growth factor IB, SKI protein, Zinc finger and BTB domain-containing...

.

Further reading

External links