Recombinant Human Pterin-4-alpha-carbinolamine dehydRatase (PCBD1)

Function

Involved in tetrahydrobiopterin biosynthesis (By similarity). Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription (By similarity). Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity (By similarity). Also acts as a coactivator for HNF1B-dependent transcription (PubMed:24204001)

Subcellular Location

Cytoplasm; Nucleus

Disease Association

Hyperphenylalaninemia, BH4-deficient, D (HPABH4D) : An autosomal recessive disease characterized by primapterinuria, a variant form of hyperphenylalaninemia defined by increased excretion of 7-substituted pterins in the urine. Patients with primapterinuria show an increased ratio of neopterin to biopterin in the urine, excretion of subnormal levels of biopterins, and normal levels of biogenic amines in cerebrospinal fluid. Neurologic signs are mild, present in the neonatal period only, and include hypotonia, delayed motor development and tremor. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Homotetramer and homodimer (By similarity). Heterotetramer with HNF1A; formed by a dimer of dimers (By similarity). Interacts with HNF1B (via HNF-p1 domain); the interaction increases HNF1B transactivation activity (PubMed:24204001)

• Mendel D.B. et al. Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. — Science (1991)
• Thoeny B. et al. Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 alpha. — Biochem. Biophys. Res. Commun. (1995)
• Lei X.D. et al. Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1. — DNA Cell Biol. (1999)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hauer C.R. et al. Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence. — J. Biol. Chem. (1993)
• Burkard T.R. et al. Initial characterization of the human central proteome. — BMC Syst. Biol. (2011)
• Bian Y. et al. An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. — J. Proteomics (2014)
• Citron B.A. et al. Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. — Am. J. Hum. Genet. (1993)