PCBD1

PCBD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DCH, 1F93, 1DCO, 1DCP
Identifiers
Aliases	PCBD1 , DCOH, PCBD, PCD, PHS, pterin-4 alpha-carbinolamine dehydratase 1
External IDs	OMIM: 126090; MGI: 94873; HomoloGene: 57028; GeneCards: PCBD1; OMA:PCBD1 - orthologs
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10q22.1 Start 70,882,280 bp [1] End 70,888,565 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 B4|10 32.14 cM Start 60,925,110 bp [2] End 60,930,103 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver body of pancreas right adrenal cortex left adrenal gland left adrenal cortex apex of heart mucosa of transverse colon body of stomach right auricle of heart muscle layer of sigmoid colon Top expressed in right kidney yolk sac proximal tubule left lobe of liver human kidney islet of Langerhans epithelium of stomach lumbar spinal ganglion migratory enteric neural crest cell Ileal epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coactivator activity phenylalanine 4-monooxygenase activity protein binding lyase activity identical protein binding 4-alpha-hydroxytetrahydrobiopterin dehydratase activity Cellular component nucleoplasm extracellular exosome nucleus cytoplasm cytosol Biological process regulation of transcription, DNA-templated protein heterooligomerization L-phenylalanine catabolic process transcription, DNA-templated positive regulation of transcription, DNA-templated tetrahydrobiopterin biosynthetic process protein homotetramerization regulation of protein homodimerization activity L-phenylalanine metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5092 13180 Ensembl ENSG00000166228 ENSMUSG00000020098 UniProt P61457 P61458 RefSeq (mRNA) NM_000281 NM_001289797 NM_001323004 NM_001001939 NM_025273 RefSeq (protein) NP_000272 NP_001276726 NP_001309933 NP_079549 Location (UCSC) Chr 10: 70.88 – 70.89 Mb Chr 10: 60.93 – 60.93 Mb PubMed search [3] [4]
Wikidata
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Pterin-4-alpha-carbinolamine dehydratase is an enzyme that in humans is encoded by the PCBD1 gene. ^{[5] [6]}

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). ^[6]

Clinical significance

Mutations of the PCBD1 gene cause pterin-4 alpha-carbinolamine dehydratase deficiency, one of the forms of tetrahydrobiopterin deficiency. ^[7]

Interactions

PCBD1 has been shown to interact with DYRK1B ^[8] and HNF1A. ^{[9] [10]}

References

1. GRCh38: Ensembl release 89: ENSG00000166228 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020098 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Milatovich A, Mendel DB, Crabtree GR, Francke U (April 1993). "Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10". Genomics. 16 (1): 292–295. doi: 10.1006/geno.1993.1182 . PMID   8486378.
6. "Entrez Gene: PCBD1 pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1)".
7. Opladen T, López-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, et al. (May 2020). "Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH₄) deficiencies". Orphanet Journal of Rare Diseases. 15 (1): 126. doi: 10.1186/s13023-020-01379-8 . PMC   7251883 . PMID   32456656.
8. Lim S, Jin K, Friedman E (July 2002). "Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha". The Journal of Biological Chemistry. 277 (28): 25040–25046. doi: 10.1074/jbc.M203257200 . PMID   11980910.
9. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
10. Sourdive DJ, Transy C, Garbay S, Yaniv M (April 1997). "The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity". Nucleic Acids Research. 25 (8): 1476–1484. doi:10.1093/nar/25.8.1476. PMC   146627 . PMID   9092652.

Further reading

• Hansen LP, Crabtree GR (April 1993). "Regulation of the HNF-1 homeodomain proteins by DCoH". Current Opinion in Genetics & Development. 3 (2): 246–253. doi:10.1016/0959-437X(93)90030-S. PMID   8504250.
• Suck D, Ficner R (June 1996). "Structure and function of PCD/DCoH, an enzyme with regulatory properties". FEBS Letters. 389 (1): 35–39. doi:10.1016/0014-5793(96)00573-X. PMID   8682201. S2CID   43378844.
• Thöny B, Auerbach G, Blau N (April 2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions". The Biochemical Journal. 347 Pt 1 (1): 1–16. doi:10.1042/0264-6021:3470001. PMC   1220924 . PMID   10727395.
• Mendel DB, Khavari PA, Conley PB, Graves MK, Hansen LP, Admon A, Crabtree GR (December 1991). "Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein". Science. 254 (5039): 1762–1767. Bibcode:1991Sci...254.1762M. doi:10.1126/science.1763325. PMID   1763325.
• Thöny B, Neuheiser F, Blau N, Heizmann CW (May 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". Biochemical and Biophysical Research Communications. 210 (3): 966–973. doi:10.1006/bbrc.1995.1751. PMID   7763270.
• Thöny B, Heizmann CW, Mattei MG (January 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): 365–368. doi:10.1006/geno.1994.1071. PMID   8188266.
• Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, Davis MD (September 1993). "Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism". American Journal of Human Genetics. 53 (3): 768–774. PMC   1682436 . PMID   8352282.
• Hauer CR, Rebrin I, Thöny B, Neuheiser F, Curtius HC, Hunziker P, et al. (March 1993). "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. doi: 10.1016/S0021-9258(18)53471-2 . PMID   8444860.
• Johnen G, Kowlessur D, Citron BA, Kaufman S (December 1995). "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. Bibcode:1995PNAS...9212384J. doi: 10.1073/pnas.92.26.12384 . PMC   40362 . PMID   8618906.
• Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Sourdive DJ, Transy C, Garbay S, Yaniv M (April 1997). "The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity". Nucleic Acids Research. 25 (8): 1476–1484. doi:10.1093/nar/25.8.1476. PMC   146627 . PMID   9092652.
• Johnen G, Kaufman S (December 1997). "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. Bibcode:1997PNAS...9413469J. doi: 10.1073/pnas.94.25.13469 . PMC   28329 . PMID   9391049.
• Thöny B, Neuheiser F, Kierat L, Blaskovics M, Arn PH, Ferreira P, et al. (June 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)". American Journal of Human Genetics. 62 (6): 1302–1311. doi:10.1086/301887. PMC   1377166 . PMID   9585615.
• Thöny B, Neuheiser F, Kierat L, Rolland MO, Guibaud P, Schlüter T, et al. (August 1998). "Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia". Human Genetics. 103 (2): 162–167. doi:10.1007/s004390050800. PMID   9760199. S2CID   7949076.
• Lei XD, Kaufman S (March 1999). "Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1". DNA and Cell Biology. 18 (3): 243–252. doi:10.1089/104454999315466. PMID   10098606.
• Waters PJ, Scriver CR, Parniak MA (July 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". Molecular Genetics and Metabolism. 73 (3): 230–238. doi:10.1006/mgme.2001.3198. PMID   11461190.