Alternative titles; symbols
HGNC Approved Gene Symbol: ONECUT2
Cytogenetic location: 18q21.31 Genomic coordinates (GRCh38) : 18:57,435,374-57,491,298 (from NCBI)
Transcription factors of the ONECUT class, the prototype of which is HNF6 (ONECUT1; 604164), are characterized by the presence of a single 'cut' domain and an atypical homeodomain. By searching a sequence database for HNF6-related proteins, Jacquemin et al. (1999) identified a human fetal retina EST encoding ONECUT2, which they called OC2. They isolated a cDNA containing a full-length ONECUT2 coding sequence. The predicted 485-amino acid ONECUT2 protein contains a single C-terminal cut domain followed by a homeodomain that is characteristic of the ONECUT class. ONECUT2 shares several regions of high sequence similarity with HNF6, including a serine/threonine- and proline-rich sequence (STP box). RT-PCR of 12 human tissues showed abundant ONECUT2 expression in liver and skin, lower expression in testis, brain (occipital cortex), and urinary bladder, and very weak expression in kidney.
By radiation hybrid mapping, Jacquemin et al. (1999) mapped the ONECUT2 gene to 18q21.1-q21.2.
Jacquemin et al. (1999) showed that the recognition properties of ONECUT2 for binding sites present in regulatory regions of liver-expressed genes differ from, but overlap with, those of HNF6. Like HNF6, recombinant ONECUT2 stimulated transcription of the HNF3-beta gene. Jacquemin et al. (1999) suggested that ONECUT2 participates in the network of transcription factors required for liver differentiation and metabolism.
Plaisance et al. (2006) found that increased expression of microRNA-9 (MIRN9; see 611186), which is expressed in neurons and beta cells, results in drastic impairment of glucose-stimulated insulin release. This perturbation of the secretory functions was associated with an increase in the level of granuphilin (SYTL4; 300723), a Rab3/Rab27 effector playing a negative modulatory role on insulin exocytosis. Plaisance et al. (2006) identified the ONECUT2 transcription factor as a target of MIRN9 and demonstrated that this factor exhibits a repressor activity on granuphilin expression. Silencing of OC2 mimicked the effects of MIRN9 on stimulus-induced exocytosis and on granuphilin expression. Conversely, overexpression of OC2 repressed granuphilin expression.
Jacquemin, P., Lannoy, V. J., Rousseau, G. G., Lemaigre, F. P. OC-2, a novel mammalian member of the ONECUT class of homeodomain transcription factors whose function in liver partially overlaps with that of hepatocyte nuclear factor-6. J. Biol. Chem. 274: 2665-2671, 1999. [PubMed: 9915796] [Full Text: https://doi.org/10.1074/jbc.274.5.2665]
Plaisance, V., Abderrahmani, A., Perret-Menoud, V., Jacquemin, P., Lemaigre, F., Regazzi, R. MicroRNA-9 controls the expression of granuphilin/slp4 and the secretory response of insulin-producing cells. J. Biol. Chem. 281: 26932-26942, 2006. [PubMed: 16831872] [Full Text: https://doi.org/10.1074/jbc.M601225200]