PCBD1 explained

Pterin-4-alpha-carbinolamine dehydratase is an enzyme that in humans is encoded by the PCBD1 gene.^{[1] [2]}

Function

This gene encodes pterin-4 alpha-carbinolamine dehydratase, an enzyme involved in phenylalanine hydroxylation. The enzyme regulates the homodimerization of the transcription factor hepatocyte nuclear factor 1 (HNF1).

Clinical significance

Mutations of the PCBD1 gene cause pterin-4 alpha-carbinolamine dehydratase deficiency, one of the forms of tetrahydrobiopterin deficiency.^[3]

Interactions

PCBD1 has been shown to interact with DYRK1B^[4] and HNF1A.^{[5] [6]}

Further reading

• Hansen LP, Crabtree GR . Regulation of the HNF-1 homeodomain proteins by DCoH . Current Opinion in Genetics & Development . 3 . 2 . 246–253 . April 1993 . 8504250 . 10.1016/0959-437X(93)90030-S .
• Suck D, Ficner R . Structure and function of PCD/DCoH, an enzyme with regulatory properties . FEBS Letters . 389 . 1 . 35–39 . June 1996 . 8682201 . 10.1016/0014-5793(96)00573-X . 43378844 .
• Thöny B, Auerbach G, Blau N . Tetrahydrobiopterin biosynthesis, regeneration and functions . The Biochemical Journal . 347 Pt 1 . 1 . 1–16 . April 2000 . 10727395 . 1220924 . 10.1042/0264-6021:3470001 .
• Mendel DB, Khavari PA, Conley PB, Graves MK, Hansen LP, Admon A, Crabtree GR . Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein . Science . 254 . 5039 . 1762–1767 . December 1991 . 1763325 . 10.1126/science.1763325 . 1991Sci...254.1762M .
• Thöny B, Neuheiser F, Blau N, Heizmann CW . Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 alpha . Biochemical and Biophysical Research Communications . 210 . 3 . 966–973 . May 1995 . 7763270 . 10.1006/bbrc.1995.1751 .
• Thöny B, Heizmann CW, Mattei MG . Chromosomal location of two human genes encoding tetrahydrobiopterin-metabolizing enzymes: 6-pyruvoyl-tetrahydropterin synthase maps to 11q22.3-q23.3, and pterin-4 alpha-carbinolamine dehydratase maps to 10q22 . Genomics . 19 . 2 . 365–368 . January 1994 . 8188266 . 10.1006/geno.1994.1071 .
• Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, Davis MD . Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism . American Journal of Human Genetics . 53 . 3 . 768–774 . September 1993 . 8352282 . 1682436 .
• Hauer CR, Rebrin I, Thöny B, Neuheiser F, Curtius HC, Hunziker P, Blau N, Ghisla S, Heizmann CW . 6 . Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence . The Journal of Biological Chemistry . 268 . 7 . 4828–4831 . March 1993 . 8444860 . 10.1016/S0021-9258(18)53471-2 . free .
• Johnen G, Kowlessur D, Citron BA, Kaufman S . Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia . Proceedings of the National Academy of Sciences of the United States of America . 92 . 26 . 12384–12388 . December 1995 . 8618906 . 40362 . 10.1073/pnas.92.26.12384 . 1995PNAS...9212384J . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Sourdive DJ, Transy C, Garbay S, Yaniv M . The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity . Nucleic Acids Research . 25 . 8 . 1476–1484 . April 1997 . 9092652 . 146627 . 10.1093/nar/25.8.1476 .
• Johnen G, Kaufman S . Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1 . Proceedings of the National Academy of Sciences of the United States of America . 94 . 25 . 13469–13474 . December 1997 . 9391049 . 28329 . 10.1073/pnas.94.25.13469 . 1997PNAS...9413469J . free .
• Thöny B, Neuheiser F, Kierat L, Blaskovics M, Arn PH, Ferreira P, Rebrin I, Ayling J, Blau N . 6 . Hyperphenylalaninemia with high levels of 7-biopterin is associated with mutations in the PCBD gene encoding the bifunctional protein pterin-4a-carbinolamine dehydratase and transcriptional coactivator (DCoH) . American Journal of Human Genetics . 62 . 6 . 1302–1311 . June 1998 . 9585615 . 1377166 . 10.1086/301887 .
• Thöny B, Neuheiser F, Kierat L, Rolland MO, Guibaud P, Schlüter T, Germann R, Heidenreich RA, Duran M, de Klerk JB, Ayling JE, Blau N . 6 . Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia . Human Genetics . 103 . 2 . 162–167 . August 1998 . 9760199 . 10.1007/s004390050800 . 7949076 .
• Lei XD, Kaufman S . Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1 . DNA and Cell Biology . 18 . 3 . 243–252 . March 1999 . 10098606 . 10.1089/104454999315466 .
• Waters PJ, Scriver CR, Parniak MA . Homomeric and heteromeric interactions between wild-type and mutant phenylalanine hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis of mutations causing hyperphenylalaninemia . Molecular Genetics and Metabolism . 73 . 3 . 230–238 . July 2001 . 11461190 . 10.1006/mgme.2001.3198 .

Notes and References

1. Milatovich A, Mendel DB, Crabtree GR, Francke U . Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10 . Genomics . 16 . 1 . 292–295 . April 1993 . 8486378 . 10.1006/geno.1993.1182 . free .
2. Web site: Entrez Gene: PCBD1 pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1).
3. Opladen T, López-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, Assmann B, Kurian MA, Leuzzi V, Heales S, Pope S, Porta F, García-Cazorla A, Honzík T, Pons R, Regal L, Goez H, Artuch R, Hoffmann GF, Horvath G, Thöny B, Scholl-Bürgi S, Burlina A, Verbeek MM, Mastrangelo M, Friedman J, Wassenberg T, Jeltsch K, Kulhánek J, Kuseyri Hübschmann O . 6 . Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH₄) deficiencies . Orphanet Journal of Rare Diseases . 15 . 1 . 126 . May 2020 . 32456656 . 7251883 . 10.1186/s13023-020-01379-8 . free .
4. Lim S, Jin K, Friedman E . Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha . The Journal of Biological Chemistry . 277 . 28 . 25040–25046 . July 2002 . 11980910 . 10.1074/jbc.M203257200 . free .
5. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . 6 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
6. Sourdive DJ, Transy C, Garbay S, Yaniv M . The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity . Nucleic Acids Research . 25 . 8 . 1476–1484 . April 1997 . 9092652 . 146627 . 10.1093/nar/25.8.1476 .