The reference OMIM entry for this protein is 126090

Pterin-4-alpha-carbinolamine dehydratase 1; pcbd1
Pcbd
Dimerization cofactor of hepatic nuclear factor 1-alpha; dcoh

DESCRIPTION

The PCBD1 gene encodes a bifunctional protein that acts as an enzyme in the salvage pathway for regeneration of tetrahydrobiopterin (BH4), the cofactor for aromatic amino acid hydroxylases. It also acts as a binding partner of the HNF1 family of transcription factors (see 142410) (Thony et al., 1998). Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 (PCBD/DCOH) is a dual-function protein. In the cytoplasm it acts as a dehydratase in the regeneration of BH4, whereas in the nucleus, it functions as a dimerization cofactor of HNF1 and increases the transcriptional activity of HNF1 (Lei and Kaufman, 1999).

CLONING

Dimerization among transcription factors is a recurrent theme in the regulation of eukaryotic gene expression. HNF1 is a homeodomain-containing protein that functions as a dimer. Mendel et al. (1991) identified a dimerization cofactor of HNF-1-alpha (DCOH) that displayed a restricted tissue distribution. Hauer et al. (1993) isolated cDNA clones corresponding to the pterin-4-alpha-carbinolamine dehydratase gene from a human liver cDNA library. The human and rat proteins have identical sequences and a molecular mass of 11.9 kD. The PCBD1 protein was identical to the dimerization cofactor reported by Mendel et al. (1991). The protein was found to exist as a tetramer. Lei and Kaufman (1999) found that human PCBD/DCOH was present predominantly in liver and kidney, with significant amounts in testis and ovary, trace amounts in lung, and undetectable levels in whole brain, heart, and spleen. It was expressed in all of the cells that were examined. It was also present in the nucleus of HeLa cells, which lack HNF1, and in the cytoplasm of fibroblasts, that have little or no BH4. Although the mRNA level in liver was only 4-fold higher than that in keratinocytes and fibroblasts, the hepatic protein level was 20-fold higher than that in keratinocytes and dermal fibroblasts. Further studies showed that the untranslated region of human keratinocyte PCBD had 53 bp more than the liver PCBD, which made a difference in translation efficiency. These data show that PCBD is a widely distributed protein, with differential expression in different tissues and cells that is regulated at both the transcriptional and translational levels. In mice, Ferre et al. (2014) found expression of the Pcbd1 gene in kidney, liver, and pancreatic cells. Pcbd1 localized mostly to the distal convoluted tubule, but als to the cortical thick ascending loop of Henle and connecting tubule. Simaite et al. (2014) found expression of the Pcbd1 gene in the developing pancreas of both mice and Xenopus. Pcbd1 accumulated in endocrine progenitor cells and endoderm in Xenopus, and in endocrine progenitor cells and pancreatic epithelium in mice.

GENE STRUCTURE

Using a previously isolated cDNA as a probe, Thony et al. (1995) isolated and determined the complete nucleotide sequence and flanking regions of the single human PCBD gene. The protein coding region of the gene is about 5 kb long and contains 4 exons. The 5-prime flanking sequence was studied, and binding sites for several transcriptional regulators were found.

GENE FUNCTION

Mendel et al. (1991) found that DCOH did not bind to DNA but, rather, to selectively stabilized HNF1A dimers. In mice, Ferre et al. (2014) found expression of Pcbd1 mostly in the distal convoluted tubule of the kidney. Pcbd1 expression increased when mice were fed a low magnesium diet, su ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 126090 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).