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P09417 (DHPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydropteridine reductase

EC=1.5.1.34
Alternative name(s):
HDHPR
Quinoid dihydropteridine reductase
Gene names
Name:QDPR
Synonyms:DHPR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length244 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Hyperphenylalaninemia, BH4-deficient, C (HPABH4C) [MIM:261630]: 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. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.17 Ref.18 Ref.19 Ref.20

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Ontologies

Keywords
   Biological processTetrahydrobiopterin biosynthesis
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Phenylketonuria
   LigandNADP
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processL-phenylalanine catabolic process

Traceable author statement. Source: Reactome

cellular amino acid metabolic process

Traceable author statement Ref.3. Source: ProtInc

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

dihydrobiopterin metabolic process

Traceable author statement Ref.3. Source: ProtInc

liver development

Inferred from electronic annotation. Source: Ensembl

response to aluminum ion

Inferred from electronic annotation. Source: Ensembl

response to glucagon

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

tetrahydrobiopterin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay. Source: LIFEdb

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from electronic annotation. Source: Ensembl

   Molecular_function6,7-dihydropteridine reductase activity

Inferred from experiment. Source: Reactome

NADH binding

Inferred from electronic annotation. Source: Ensembl

NADPH binding

Inferred from electronic annotation. Source: Ensembl

electron carrier activity

Traceable author statement Ref.3. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 244243Dihydropteridine reductase
PRO_0000054636

Regions

Nucleotide binding14 – 3825NADP

Sites

Active site1501Proton acceptor

Amino acid modifications

Modified residue21N-acetylalanine Ref.10 Ref.11 Ref.13 Ref.14
Modified residue731N6-succinyllysine By similarity
Modified residue791N6-succinyllysine By similarity
Modified residue961N6-succinyllysine By similarity
Modified residue1021N6-succinyllysine By similarity

Natural variations

Natural variant141L → P in HPABH4C; severe. Ref.19
VAR_008121
Natural variant171G → R in HPABH4C; severe. Ref.20
VAR_021767
Natural variant171G → V in HPABH4C; severe. Ref.19
VAR_008122
Natural variant181G → D in HPABH4C; severe. Ref.20
VAR_021768
Natural variant231G → D in HPABH4C; severe. Ref.4 Ref.17 Ref.20
VAR_006960
Natural variant361W → R in HPABH4C.
VAR_006961
Natural variant511S → T. Ref.1 Ref.3 Ref.4
VAR_013027
Natural variant661Q → R in HPABH4C; severe. Ref.20
VAR_021769
Natural variant741L → P in HPABH4C.
VAR_006962
Natural variant1081W → G in HPABH4C. Ref.17
VAR_006963
Natural variant1231T → TT in HPABH4C. Ref.18
VAR_006964
Natural variant1451P → L in HPABH4C.
VAR_006965
Natural variant1491G → R in HPABH4C. Ref.20
VAR_021770
Natural variant1501Y → C in HPABH4C; mild. Ref.4 Ref.20
VAR_006966
Natural variant1511G → S in HPABH4C; mild.
VAR_006967
Natural variant1581H → Y in HPABH4C; severe. Ref.4
VAR_006968
Natural variant1701G → S in HPABH4C.
VAR_006969
Natural variant2121F → C in HPABH4C; mild.
VAR_006970
Natural variant2181G → GITG in HPABH4C; mild.
VAR_006971

Secondary structure

.................................... 244
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09417 [UniParc].

Last modified November 28, 2006. Version 2.
Checksum: 0852F9F0CA38AB1C

FASTA24425,790
        10         20         30         40         50         60 
MAAAAAAGEA RRVLVYGGRG ALGSRCVQAF RARNWWVASV DVVENEEASA SIIVKMTDSF 

        70         80         90        100        110        120 
TEQADQVTAE VGKLLGEEKV DAILCVAGGW AGGNAKSKSL FKNCDLMWKQ SIWTSTISSH 

       130        140        150        160        170        180 
LATKHLKEGG LLTLAGAKAA LDGTPGMIGY GMAKGAVHQL CQSLAGKNSG MPPGAAAIAV 

       190        200        210        220        230        240 
LPVTLDTPMN RKSMPEADFS SWTPLEFLVE TFHDWITGKN RPSSGSLIQV VTTEGRTELT 


PAYF 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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 T.-O., 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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] [Europe PMC] [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, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Colon carcinoma.
[11]"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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[16]"Molecular basis of dihydropteridine reductase deficiency."
Smooker P.M., Cotton R.G.H.
Hum. Mutat. 5:279-284(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[17]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4C ASP-23 AND GLY-108.
[18]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HPABH4C THR-123 INS.
[19]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4C PRO-14 AND VAL-17.
[20]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4C ARG-17; ASP-18; ASP-23; ARG-66; ARG-149 AND CYS-150.
+Additional computationally mapped references.

Web resources

BIOMDB

Db of mutations causing tetrahydrobiopterin deficiencies

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04882 mRNA. Translation: CAA28571.1.
M16447 mRNA. Translation: AAA52305.1.
AJ006239 expand/collapse EMBL AC list , AJ006240, AJ006241, AJ006242, AJ006243, AJ006244, 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.
PIRRDHUP. A93655.
RefSeqNP_000311.2. NM_000320.2.
UniGeneHs.75438.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HDRX-ray2.50A1-244[»]
ProteinModelPortalP09417.
SMRP09417. Positions 9-244.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111798. 8 interactions.
IntActP09417. 2 interactions.
MINTMINT-5002411.
STRING9606.ENSP00000281243.

Chemistry

BindingDBP09417.
ChEMBLCHEMBL3730.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP09417.

Polymorphism databases

DMDM118572639.

2D gel databases

REPRODUCTION-2DPAGEIPI00014439.
UCD-2DPAGEP09417.

Proteomic databases

PaxDbP09417.
PeptideAtlasP09417.
PRIDEP09417.

Protocols and materials databases

DNASU5860.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281243; ENSP00000281243; ENSG00000151552.
GeneID5860.
KEGGhsa:5860.
UCSCuc003gpd.3. human.

Organism-specific databases

CTD5860.
GeneCardsGC04M017488.
HGNCHGNC:9752. QDPR.
HPAHPA058951.
MIM261630. phenotype.
612676. gene.
neXtProtNX_P09417.
Orphanet226. Dihydropteridine reductase deficiency.
PharmGKBPA34094.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1028.
HOGENOMHOG000232194.
HOVERGENHBG001000.
InParanoidP09417.
KOK00357.
OMASDLMWKQ.
OrthoDBEOG7060RV.
PhylomeDBP09417.
TreeFamTF105932.

Enzyme and pathway databases

BioCycMetaCyc:HS07746-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP09417.

Gene expression databases

ArrayExpressP09417.
BgeeP09417.
CleanExHS_QDPR.
GenevestigatorP09417.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
[Graphical view]
PROSITEPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSQDPR. human.
EvolutionaryTraceP09417.
GeneWikiQDPR.
GenomeRNAi5860.
NextBio22758.
PROP09417.
SOURCESearch...

Entry information

Entry nameDHPR_HUMAN
AccessionPrimary (citable) accession number: P09417
Secondary accession number(s): A8K158, Q53F52, Q9H3M5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 28, 2006
Last modified: April 16, 2014
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM