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nuclear receptor corepressor 2; N-CoR2; silencing mediator of retinoic acid & thyroid hormone receptor; SMRT; thyroid-, retinoic-acid-receptor-associated corepressor; T3 receptor-associating factor; TRAC; CTG repeat protein 26; SMAP270 (NCOR2, CTG26)

Function: - interacts with unliganded nuclear receptors, including RXR, RAR, T3R, PPAR-alpha & PPAR-gamma to keep them in a repressed state - mediates transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription - isoform 1 & isoform 5 have different affinities for different nuclear receptors - interacts with HDAC7 (putative) - forms a large corepressor complex that contains SIN3A/B & histone deacetylases HDAC1 & HDAC2 - this complex associates with the thyroid hormone receptor (erbA) and the retinoid acid receptors (RAR) in the absence of ligand, & may stabilize their interaction with TFIIB - isoform SRMT interacts with HDAC10 - interacts with MINT - component of the N-cor repressor complex - interacts with CBFA2T3 - interacts with C1D - interacts with ATXN1L - interacts with BCL6 (directly) Structure: - the N-terminal region contains repression functions that are divided into 3 independent repression domains (RD1, RD2 & RD3) - the C-terminal region contains the nuclear receptor-interacting domains that are divided in 2 separate interaction domains (ID1 & ID2) - the 2 interaction domains (ID) contain a conserved sequence referred to as the CORNR box a) the CORNR box is required & sufficient to permit binding to unligated erbA & RAR b) sequences flanking the CORNR box determine nuclear hormone receptor specificity - belongs to the N-CoR nuclear receptor corepressors family - contains 2 SANT domains Compartment: nucleus Alternative splicing: - named isoforms=5 - contains only the C-terminal receptor-interacting domain & acts as an antirepressor Expression: - ubiquitous - high levels of expression are detected in lung, spleen & brain - regulated during cell cycle progression Pathology: - loss of NCOR2 expression may accelerate resistance to androgen deprivation therapy in prostate cancer [3]

General

nuclear receptor corepressor (N-COR) phosphoprotein

Properties

SIZE: entity length = 2525 aa MW = 275 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S54} Ser phosphorylation site {S67} Ser phosphorylation site {S149} Ser phosphorylation site {S152} Thr phosphorylation site {T156} coiled coil {174-215} MOTIF: Ser phosphorylation site {S215} SIN3A/B interaction {254-312} SANT 1 {427-478} glutamine-rich region {494-510} MOTIF: glutamine residue (SEVERAL) coiled coil {522-561} MOTIF: Thr phosphorylation site {T553} Ser phosphorylation site {S554} SANT 2 {610-661} lysine-rich region {682-685} MOTIF: lysine residue (SEVERAL) Ser phosphorylation site {S745} Ser phosphorylation site {S746} Ser phosphorylation site {S750} Ser phosphorylation site {S753} proline-rich region SITE: 778-820 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S864} Ser phosphorylation site {S939} Ser phosphorylation site {S956} proline-rich region SITE: 995-1003 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S1259} Ser phosphorylation site {S1261} Ser phosphorylation site {S1331} Thr phosphorylation site {T1391} proline-rich region SITE: 1392-1397 MOTIF: proline residue (SEVERAL) Thr phosphorylation site {T1444} Ser phosphorylation site {S1487} Ser phosphorylation site {S1584} Ser phosphorylation site {S1786} glycine-rich region {1850-1854} Ser phosphorylation site {S1982} Ser phosphorylation site {S2016} Tyr phosphorylation site {Y2051} Ser phosphorylation site {S2057} Ser phosphorylation site {S2065} Ser phosphorylation site {S2068} Ser phosphorylation site {S2069} Ser phosphorylation site {S2071} Thr phosphorylation site {T2073} CORNR box of ID1 {2147-2151} Ser phosphorylation site {S2205} Ser phosphorylation site {S2208} Ser phosphorylation site {S2234} Ser phosphorylation site {S2269} CORNR box of ID2 {2350-2354} Ser phosphorylation site {S2463} proline-rich region SITE: 2487-2490 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S2522} Ser phosphorylation site {S2524}

Database Correlations

OMIM 600848 UniProt Q9Y618 Pfam PF00249 Entrez Gene 9612 Kegg hsa:9612

References

  1. UniProt :accession Q9Y618
  2. Corton JC, Anderson SP, Stauber A. Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Annu Rev Pharmacol Toxicol. 2000;40:491-518. Review. PMID: 10836145
  3. Larkin M Loss, Mutation of NCOR2 Likely Fuels Prostate Cancer Progression, Resistance. Medscape. December 23, 2021 https://www.medscape.com/viewarticle/965465 - Long MD, Jacobi JJ, Singh PK et al Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer. Cell Reports 2021. 37(11):110109 https://www.sciencedirect.com/science/article/pii/S221112472101603X

Component-of

N-cor repressor complex