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Identification
HMDB Protein ID HMDBP00545
Secondary Accession Numbers
  • 5816
  • HMDBP06674
Name Dihydropteridine reductase
Synonyms
  1. HDHPR
  2. Quinoid dihydropteridine reductase
Gene Name QDPR
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.
Pathways
  • Dopa-responsive dystonia
  • Folate biosynthesis
  • Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
  • Hyperphenylalaninemia due to dhpr-deficiency
  • Pterine Biosynthesis
  • Segawa syndrome
  • Sepiapterin reductase deficiency
Reactions
A 5,6,7,8-tetrahydropteridine + NAD(P)(+) → a 6,7-dihydropteridine + NAD(P)H details
4a-Carbinolamine tetrahydrobiopterin + NADH + Hydrogen Ion → Tetrahydrobiopterin + NAD details
4a-Carbinolamine tetrahydrobiopterin + NADPH + Hydrogen Ion → Tetrahydrobiopterin + NADP details
GO Classification
Biological Process
cellular nitrogen compound metabolic process
cellular response to drug
response to glucagon stimulus
liver development
response to lead ion
response to aluminum ion
dihydrobiopterin metabolic process
tetrahydrobiopterin biosynthetic process
L-phenylalanine catabolic process
Cellular Component
cytosol
mitochondrion
Function
catalytic activity
oxidoreductase activity
Molecular Function
electron carrier activity
6,7-dihydropteridine reductase activity
NADH binding
NADPH binding
Process
metabolic process
Cellular Location Not Available
Gene Properties
Chromosome Location 4
Locus 4p15.31
SNPs QDPR
Gene Sequence
>735 bp
ATGGCGGCGGCGGCGGCTGCAGGCGAGGCGCGCCGGGTGCTGGTGTACGGCGGCAGGGGC
GCTCTGGGTTCTCGATGCGTGCAGGCTTTTCGGGCCCGCAACTGGTGGGTTGCCAGCGTT
GATGTGGTGGAGAATGAAGAGGCCAGCGCTACGATCATTGTTAAAATGACAGACTCGTTC
ACTGAGCAGGCTGACCAGGTGACTGCTGAGGTTGGAAAGCTCTTGGGTGAAGAGAAGGTG
GATGCAATTCTTTGCGTTGCTGGAGGATGGGCCGGGGGCAATGCCAAATCCAAGTCTCTC
TTTAAGAACTGTGACCTGATGTGGAAGCAGAGCATATGGACATCGACCATCTCCAGCCAT
CTGGCTACCAAGCATCTCAAGGAAGGAGGCCTCCTGACCTTGGCTGGCGCAAAGGCTGCC
CTGGATGGGACTCCTGGTATGATCGGGTACGGCATGGCCAAGGGTGCTGTTCACCAGCTC
TGCCAGAGCCTGGCTGGGAAGAACAGCGGCATGCCGCCCGGGGCAGCCGCCATCGCTGTG
CTCCCGGTTACCCTGGATACCCCGATGAACAGGAAATCAATGCCTGAGGCTGACTTCAGC
TCCTGGACACCCTTAGAATTCCTAGTTGAAACTTTCCATGACTGGATCACAGGGAAAAAC
CGACCGAGCTCAGGAAGCCTAATCCAGGTGGTAACCACAGAAGGAAGGACGGAACTCACC
CCAGCATATTTTTAG
Protein Properties
Number of Residues 244
Molecular Weight 25789.295
Theoretical pI 7.367
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Dihydropteridine reductase
MAAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWVASVDVVENEEASASIIVKMTDSF
TEQADQVTAEVGKLLGEEKVDAILCVAGGWAGGNAKSKSLFKNCDLMWKQSIWTSTISSH
LATKHLKEGGLLTLAGAKAALDGTPGMIGYGMAKGAVHQLCQSLAGKNSGMPPGAAAIAV
LPVTLDTPMNRKSMPEADFSSWTPLEFLVETFHDWITGKNRPSSGSLIQVVTTEGRTELT
PAYF
GenBank ID Protein 30819
UniProtKB/Swiss-Prot ID P09417
UniProtKB/Swiss-Prot Entry Name DHPR_HUMAN
PDB IDs
GenBank Gene ID X04882
GeneCard ID QDPR
GenAtlas ID QDPR
HGNC ID HGNC:9752
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  4. Dahl HH, Hutchison W, McAdam W, Wake S, Morgan FJ, Cotton RG: Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleic Acids Res. 1987 Mar 11;15(5):1921-32. [PubMed:3031582 ]
  5. Lockyer J, Cook RG, Milstien S, Kaufman S, Woo SL, Ledley FD: Structure and expression of human dihydropteridine reductase. Proc Natl Acad Sci U S A. 1987 May;84(10):3329-33. [PubMed:3033643 ]
  6. Dianzani I, de Sanctis L, Smooker PM, Gough TJ, Alliaudi C, Brusco A, Spada M, Blau N, Dobos M, Zhang HP, Yang N, Ponzone A, Armarego WL, Cotton RG: Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat. 1998;12(4):267-73. [PubMed:9744478 ]
  7. Su Y, Varughese KI, Xuong NH, Bray TL, Roche DJ, Whiteley JM: The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue. J Biol Chem. 1993 Dec 25;268(36):26836-41. [PubMed:8262916 ]
  8. Smooker PM, Cotton RG: Molecular basis of dihydropteridine reductase deficiency. Hum Mutat. 1995;5(4):279-84. [PubMed:7627180 ]
  9. Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, Cotton RG: Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J Med Genet. 1993 Jun;30(6):465-9. [PubMed:8326489 ]
  10. Howells DW, Forrest SM, Dahl HH, Cotton RG: Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am J Hum Genet. 1990 Aug;47(2):279-85. [PubMed:2116088 ]
  11. Smooker PM, Gough TJ, Cotton RG, Alliaudi C, de Sanctis L, Dianzani I: A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects. Mutations in brief no. 244. Online. Hum Mutat. 1999;13(6):503-4. [PubMed:10408783 ]
  12. Romstad A, Kalkanoglu HS, Coskun T, Demirkol M, Tokatli A, Dursun A, Baykal T, Ozalp I, Guldberg P, Guttler F: Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE). Hum Genet. 2000 Dec;107(6):546-53. [PubMed:11153907 ]