Reviewed,
UniProtKB/Swiss-Prot P09417 (DHPR_HUMAN)
Last modified
January 19, 2010.
Version 122.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Dihydropteridine reductase EC=1.5.1.34 Alternative name(s): HDHPR Quinoid dihydropteridine reductase | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 244 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. |
| Catalytic activity | A 5,6,7,8-tetrahydropteridine + NAD(P)+ = a 6,7-dihydropteridine + NAD(P)H. |
| Subunit structure | Homodimer. |
| Involvement in disease | Defects in QDPR are the cause of BH4-deficient hyperphenylalaninemia type C (HPABH4C) [MIM:261630]; also called dihydropteridine reductase deficiency (DHPR deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to DHPR deficiency or quinoid dihydropteridine reductase deficiency (QDPR deficiency). HPABH4C is a rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. These patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated. Ref.4 Ref.15 Ref.16 Ref.17 Ref.18 |
| Sequence similarities | Belongs to the short-chain dehydrogenases/reductases (SDR) family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Tetrahydrobiopterin biosynthesis |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation Phenylketonuria |
| Ligand | NADP |
| Molecular function | Oxidoreductase |
| PTM | Acetylation |
| Technical term | 3D-structure Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | cellular amino acid metabolic process Ref.3 Traceable author statement. Source: ProtInc dihydrobiopterin metabolic process Ref.3Traceable author statement. Source: ProtInc oxidation reductionInferred from electronic annotation. Source: UniProtKB-KW tetrahydrobiopterin biosynthetic processInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytoplasm Inferred from direct assay. Source: LIFEdb |
| Molecular function | 6,7-dihydropteridine reductase activity Ref.3 Traceable author statement. Source: ProtInc bindingInferred from electronic annotation. Source: InterPro electron carrier activity Ref.3Traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed Ref.10 | |||||||||||||||||||||||||||||||||||||||||
| Chain | 2 – 244 | 243 | Dihydropteridine reductase | PRO_0000054636 | ||||||||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 14 – 38 | 25 | NADP | |||||||||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||||||||
| Active site | 150 | 1 | Proton acceptor | |||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 2 | 1 | N-acetylalanine Ref.10 Ref.12 | |||||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 14 | 1 | L → P in HPABH4C; severe. Ref.17 | VAR_008121 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 17 | 1 | G → R in HPABH4C; severe. Ref.18 | VAR_021767 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 17 | 1 | G → V in HPABH4C; severe. Ref.17 | VAR_008122 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 18 | 1 | G → D in HPABH4C; severe. Ref.18 | VAR_021768 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 23 | 1 | G → D in HPABH4C; severe. Ref.4 Ref.15 Ref.18 | VAR_006960 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 36 | 1 | W → R in HPABH4C. | VAR_006961 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 51 | 1 | S → T | VAR_013027 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 66 | 1 | Q → R in HPABH4C; severe. Ref.18 | VAR_021769 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 74 | 1 | L → P in HPABH4C. | VAR_006962 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 108 | 1 | W → G in HPABH4C. Ref.15 | VAR_006963 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 123 | 1 | T → TT in HPABH4C. Ref.16 | VAR_006964 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 145 | 1 | P → L in HPABH4C. | VAR_006965 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 149 | 1 | G → R in HPABH4C. Ref.18 | VAR_021770 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 150 | 1 | Y → C in HPABH4C; mild. Ref.4 Ref.18 | VAR_006966 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 151 | 1 | G → S in HPABH4C; mild. | VAR_006967 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 158 | 1 | H → Y in HPABH4C; severe. Ref.4 | VAR_006968 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 170 | 1 | G → S in HPABH4C. | VAR_006969 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 212 | 1 | F → C in HPABH4C; mild. | VAR_006970 | ||||||||||||||||||||||||||||||||||||||||
| Natural variant | 218 | 1 | G → GITG in HPABH4C; mild. | VAR_006971 | ||||||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 11 – 16 | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Turn | 17 – 19 | 3 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 21 – 32 | 12 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 36 – 43 | 8 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 48 – 53 | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 60 – 75 | 16 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 80 – 85 | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 100 – 110 | 11 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 112 – 125 | 14 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 126 – 135 | 10 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 138 – 141 | 4 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 148 – 165 | 18 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 176 – 181 | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 188 – 191 | 4 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 199 – 201 | 3 | ||||||||||||||||||||||||||||||||||||||||||
| Helix | 205 – 216 | 12 | ||||||||||||||||||||||||||||||||||||||||||
| Turn | 217 – 220 | 4 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 227 – 233 | 7 | ||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 236 – 242 | 7 | ||||||||||||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency." Dahl H.-H.M., Hutchison W., McAdam W., Wake S., Morgan F.J., Cotton R.G.H. Nucleic Acids Res. 15:1921-1932(1987) [PubMed: 3031582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-51. |
| [2] | Dahl H.-H.M. Submitted (JUL-1987) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 51. |
| [3] | "Structure and expression of human dihydropteridine reductase." Lockyer J., Cook R.G., Milstien S., Kaufman S., Woo S.L.C., Ledley F.D. Proc. Natl. Acad. Sci. U.S.A. 84:3329-3333(1987) [PubMed: 3033643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-51. |
| [4] | "Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations." Dianzani I., de Sanctis L., Smooker P.M., Gough T.J., Alliaudi C., Brusco A., Spada M., Blau N., Dobos M., Zhang H.-P., Yang N., Ponzone A., Armarego W.L.F., Cotton R.G.H. Hum. Mutat. 12:267-273(1998) [PubMed: 9744478] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-51, VARIANTS HPABH4C ASP-23; CYS-150; TYR-158 AND ILE-THR-GLY-218 INS. |
| [5] | "The complete sequence of human dihydropteridine reductase gene containing BAC clone 395N09." Hsiao K.-J., Yen P.-F., Lin C.-H., Liu T.-T., Chiang S.-H., Chen C.-Y., Tsai S.-F. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [6] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain. |
| [7] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain. |
| [10] | Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11 AND 128-138, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Colon carcinoma. |
| [11] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [12] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. |
| [13] | "The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue." Su Y., Varughese K.I., Xuong N.H., Bray T.L., Roche D.J., Whiteley J.M. J. Biol. Chem. 268:26836-26841(1993) [PubMed: 8262916] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). |
| [14] | "Molecular basis of dihydropteridine reductase deficiency." Smooker P.M., Cotton R.G.H. Hum. Mutat. 5:279-284(1995) [PubMed: 7627180] [Abstract] Cited for: REVIEW ON VARIANTS. |
| [15] | "Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency." Dianzani I., Howells D.W., Ponzone A., Saleeba J.A., Smooker P.M., Cotton R.G.H. J. Med. Genet. 30:465-469(1993) [PubMed: 8326489] [Abstract] Cited for: VARIANTS HPABH4C ASP-23 AND GLY-108. |
| [16] | "Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency." Howells D.W., Forrest S.M., Dahl H.-H.M., Cotton R.G.H. Am. J. Hum. Genet. 47:279-285(1990) [PubMed: 2116088] [Abstract] Cited for: VARIANT HPABH4C THR-123 INS. |
| [17] | "A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects." Smooker P.M., Gough T.J., Cotton R.G.H., Alliaudi C., de Sanctis L., Dianzani I. Hum. Mutat. 13:503-504(1999) [PubMed: 10408783] [Abstract] Cited for: VARIANTS HPABH4C PRO-14 AND VAL-17. |
| [18] | "Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE)." Romstad A., Kalkanoglu H.S., Coskun T., Demirkol M., Tokatli A., Dursun A., Baykal T., Oezalp I., Guldberg P., Guettler F. Hum. Genet. 107:546-553(2000) [PubMed: 11153907] [Abstract] Cited for: VARIANTS HPABH4C ARG-17; ASP-18; ASP-23; ARG-66; ARG-149 AND CYS-150. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | X04882 mRNA. Translation: CAA28571.1. M16447 mRNA. Translation: AAA52305.1. AJ006239 AJ006245 Genomic DNA. Translation: CAA06930.1. AB053170 Genomic DNA. Translation: BAB20429.1. AK223437 mRNA. Translation: BAD97157.1. AK289773 mRNA. Translation: BAF82462.1. CH471069 Genomic DNA. Translation: EAW92777.1. BC000576 mRNA. Translation: AAH00576.1. | ||||||||||||
| IPI | IPI00014439. | ||||||||||||
| PIR | RDHUP. A93655. | ||||||||||||
| RefSeq | NP_000311.2. | ||||||||||||
| UniGene | Hs.75438 | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| STRING | P09417. | ||||||||||||
2-D gel databases | |||||||||||||
| REPRODUCTION-2DPAGE | IPI00014439. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | P09417. | ||||||||||||
| PRIDE | P09417. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000281243; ENSP00000281243; ENSG00000151552; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 5860. | ||||||||||||
| KEGG | hsa:5860. | ||||||||||||
| NMPDR | fig|9606.3.peg.23962. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 5860. | ||||||||||||
| GeneCards | GC04M017097. | ||||||||||||
| H-InvDB | HIX0004120. | ||||||||||||
| HGNC | HGNC:9752. QDPR. | ||||||||||||
| MIM | 261630. phenotype. 612676. gene. | ||||||||||||
| Orphanet | 226. Dihydropteridine reductase deficiency. | ||||||||||||
| PharmGKB | PA34094. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG18413. | ||||||||||||
| HOGENOM | HBG380758. | ||||||||||||
| HOVERGEN | P09417. | ||||||||||||
| InParanoid | P09417. | ||||||||||||
| OMA | ICVAGGW. | ||||||||||||
| OrthoDB | EOG9R26D4. | ||||||||||||
| PhylomeDB | P09417. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BioCyc | MetaCyc:MONOMER-12069. | ||||||||||||
| BRENDA | 1.5.1.34. 247. | ||||||||||||
| Reactome | REACT_13. Metabolism of amino acids. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P09417. | ||||||||||||
| Bgee | P09417. | ||||||||||||
| CleanEx | HS_QDPR. | ||||||||||||
| Genevestigator | P09417. | ||||||||||||
| GermOnline | ENSG00000151552. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR002198. DH_sc/Rdtase_SDR. IPR016040. NAD(P)-bd_dom. IPR020904. Sc_DH/Rdtase_CS. [Graphical view] | ||||||||||||
| Pfam | PF00106. adh_short. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS00061. ADH_SHORT. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| DrugBank | DB00157. NADH. | ||||||||||||
| NextBio | 22758. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | DHPR_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P09417 Secondary accession number(s): A8K158, Q53F52, Q9H3M5 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


