CTBP2

CTBP2

CTBP2: Human C terminal binding protein 2
PDB Code: 2OME
Description
The C-terminal binding protein (CTBP) family includes four proteins (CTBP1 [CTBP1-L], CTBP3/BARS [CTBP1-S], CTBP2, and RIBEYE) which are implicated both in transcriptional repression via the recruitment of chromatin modifiers and in intracellular trafficking. CTBP is highly conserved in higher eukaryotes. Vertebrates contain two highly homologous CTBP protein (CTBP1 and CTBP2) while invertebrates contain a single CTBP. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases, so CTBPs might possess oxidoreductase activity . CTBP binding to cellular and viral transcriptional repressors is regulated by NAD+ and NADH, with NADH being 2 to 3 orders of magnitude more effective.
CTBPs can repress transcription in either a histone deacetylase-dependent or -independent manner, depending on the promoter context. CTBP family members bind to a short sequence motif within their protein interaction partners, Pro-X-Asp-Leu-Ser (PXDLS), which has been designated the CtBP interaction domain (CID). Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-beta and Wnt signalling pathways and cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A.
CtBP1 and CtBP2 are highly similar proteins, although evidence is emerging that their activity can be differentially regulated, particularly through the control of their subcellular localisation. CtBP2s from diverse species contain a unique N-terminus, absent in CtBP1 that plays a key role in controlling the nuclear-cytoplasmic distribution of the protein. A splice variant, called CtBP2-S lacking the N-terminal NLS and localizes to the cytoplasm has also been found.
CtBP2 is encoded by a bifunctional gene. In the retina, the ribbon synapse protein, RIBEYE, is expressed by utilization of a tissue-specific promoter located within an intron of the CtBP2 gene while CtBP2 is ubiquitously expressed from a different 5 ' promoter. CtBP2 is produced by alternate RNA splicing that eliminates the exon which encodes the N-terminal domain of RIBEYE.

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