PCBD1

Pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha

PDB rendering based on 1dch.

Available structures
PDB	1dch, 1dco, 1dcp, 1f93

Identifiers

Symbols

PCBD1; DCOH; PCBD; PCD; PHS

External IDs

OMIM: 126090 MGI: 94873 HomoloGene: 57028 GeneCards: PCBD1 Gene

EC number

4.2.1.96

Gene Ontology
Molecular function	• transcription coactivator activity • phenylalanine 4-monooxygenase activity • protein binding • 4-alpha-hydroxytetrahydrobiopterin dehydratase activity • lyase activity • identical protein binding
Cellular component	• nucleus • cytoplasm • cytosol
Biological process	• regulation of transcription, DNA-dependent • L-phenylalanine catabolic process • tetrahydrobiopterin biosynthetic process • cellular nitrogen compound metabolic process • regulation of protein homodimerization activity • protein homotetramerization • protein heterooligomerization
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
72.64 – 72.65 Mb

Chr 10:
60.55 – 60.56 Mb

PubMed search

[1]

[2]

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

This gene encodes pterin-4 alpha-carbinolamine dehydratase, an enzyme involved in phenylalanine hydroxylation. A deficiency of this enzyme leads to hyperphenylalaninemia. The enzyme regulates the homodimerization of the transcription factor hepatocyte nuclear factor 1 (HNF1).^[2]

Interactions

PCBD1 has been shown to interact with DYRK1B^[3] and HNF1A.^[4]^[5]

References

^ Milatovich A, Mendel DB, Crabtree GR, Francke U (Jun 1993). "Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10". Genomics 16 (1): 292–5. doi:10.1006/geno.1993.1182. PMID 8486378.
^ ^a ^b "Entrez Gene: PCBD1 pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5092.
^ Lim, Seunghwan; Jin Kideok, Friedman Eileen (Jul. 2002). "Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha". J. Biol. Chem. (United States) 277 (28): 25040–6. doi:10.1074/jbc.M203257200. ISSN 0021-9258. PMID 11980910.
^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
^ Sourdive, D J; Transy C, Garbay S, Yaniv M (Apr. 1997). "The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity". Nucleic Acids Res. (ENGLAND) 25 (8): 1476–84. doi:10.1093/nar/25.8.1476. ISSN 0305-1048. PMC 146627. PMID 9092652. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=146627.

Hansen LP, Crabtree GR (1993). "Regulation of the HNF-1 homeodomain proteins by DCoH". Curr. Opin. Genet. Dev. 3 (2): 246–53. doi:10.1016/0959-437X(93)90030-S. PMID 8504250.
Suck D, Ficner R (1996). "Structure and function of PCD/DCoH, an enzyme with regulatory properties". FEBS Lett. 389 (1): 35–9. doi:10.1016/0014-5793(96)00573-X. PMID 8682201.
Thöny B, Auerbach G, Blau N (2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions". Biochem. J. 347 (1): 1–16. doi:10.1042/0264-6021:3470001. PMC 1220924. PMID 10727395. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1220924.
Mendel DB; Khavari PA; Conley PB et al. (1992). "Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein". Science 254 (5039): 1762–7. doi:10.1126/science.1763325. PMID 1763325.
Thöny B, Neuheiser F, Blau N, Heizmann CW (1995). "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. 210 (3): 966–73. doi:10.1006/bbrc.1995.1751. PMID 7763270.
Thöny B, Heizmann CW, Mattei MG (1994). "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): 365–8. doi:10.1006/geno.1994.1071. PMID 8188266.
Citron BA; Kaufman S; Milstien S et al. (1993). "Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism". Am. J. Hum. Genet. 53 (3): 768–74. PMC 1682436. PMID 8352282. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1682436.
Hauer CR; Rebrin I; Thöny B et al. (1993). "Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence". J. Biol. Chem. 268 (7): 4828–31. PMID 8444860.
Johnen G, Kowlessur D, Citron BA, Kaufman S (1996). "Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12384–8. doi:10.1073/pnas.92.26.12384. PMC 40362. PMID 8618906. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40362.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Sourdive DJ, Transy C, Garbay S, Yaniv M (1997). "The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity". Nucleic Acids Res. 25 (8): 1476–84. doi:10.1093/nar/25.8.1476. PMC 146627. PMID 9092652. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=146627.
Johnen G, Kaufman S (1998). "Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1". Proc. Natl. Acad. Sci. U.S.A. 94 (25): 13469–74. doi:10.1073/pnas.94.25.13469. PMC 28329. PMID 9391049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=28329.
Thöny B; Neuheiser F; Kierat L et al. (1998). "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)". Am. J. Hum. Genet. 62 (6): 1302–11. doi:10.1086/301887. PMC 1377166. PMID 9585615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1377166.
Thöny B; Neuheiser F; Kierat L et al. (1998). "Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia". Hum. Genet. 103 (2): 162–7. doi:10.1007/s004390050800. PMID 9760199.
Lei XD, Kaufman S (1999). "Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1". DNA Cell Biol. 18 (3): 243–52. doi:10.1089/104454999315466. PMID 10098606.
Waters PJ, Scriver CR, Parniak MA (2001). "Homomeric and heteromeric interactions between wild-type and mutant phenylalanine hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis of mutations causing hyperphenylalaninemia". Mol. Genet. Metab. 73 (3): 230–8. doi:10.1006/mgme.2001.3198. PMID 11461190.

PDB gallery

1dch: CRYSTAL STRUCTURE OF DCOH, A BIFUNCTIONAL, PROTEIN-BINDING TRANSCRIPTION COACTIVATOR

1dco: DCOH, A BIFUNCTIONAL PROTEIN-BINDING TRANSCRIPTIONAL COACTIVATOR

1dcp: DCOH, A BIFUNCTIONAL PROTEIN-BINDING TRANSCRIPTIONAL COACTIVATOR, COMPLEXED WITH BIOPTERIN

1f93: CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH

Metabolism of vitamins, coenzymes, and cofactors

Fat soluble vitamins

Vitamin A	Retinol binding protein

Vitamin E	Alpha-tocopherol transfer protein

Vitamin D	liver (Sterol 27-hydroxylase or CYP27A1) · renal (25-Hydroxyvitamin D₃ 1-alpha-hydroxylase or CYP27B1) · degradation (1,25-Dihydroxyvitamin D₃ 24-hydroxylase or CYP24A1)

Vitamin K	Vitamin K epoxide reductase

Water soluble vitamins

Thiamine (B₁)	Thiamine diphosphokinase

Niacin (B₃)	Indoleamine 2,3-dioxygenase · Formamidase

Pantothenic acid (B₅)	Pantothenate kinase

Folic acid (B₉)	Dihydropteroate synthase · Dihydrofolate reductase · Serine hydroxymethyltransferase Methylenetetrahydrofolate reductase

Vitamin B₁₂	MMAA · MMAB · MMACHC · MMADHC

Vitamin C	L-gulonolactone oxidase

Riboflavin (B₂)	Riboflavin kinase

Nonvitamin cofactors

Tetrahydrobiopterin	GTP cyclohydrolase I · 6-pyruvoyltetrahydropterin synthase · Sepiapterin reductase PCBD1 · PTS · QDPR

Molybdenum cofactor	MOCS1 · MOCS2 · MOCS3 · GPHN

M: NUT

cof, enz, met

noco, nuvi, sysi/epon, met

drug(A8/11/12)

PCBD1

Interactions

References

Further reading