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Protein

Dihydropteridine reductase

Gene

QDPR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.

Catalytic activityi

A 5,6,7,8-tetrahydropteridine + NAD(P)+ = a 6,7-dihydropteridine + NAD(P)H.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei150Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi14 – 38NADPAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processTetrahydrobiopterin biosynthesis
LigandNADP

Enzyme and pathway databases

BioCyciMetaCyc:HS07746-MONOMER.
BRENDAi1.5.1.34. 2681.
ReactomeiR-HSA-71182. Phenylalanine and tyrosine catabolism.
SABIO-RKiP09417.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropteridine reductase (EC:1.5.1.34)
Alternative name(s):
HDHPR
Quinoid dihydropteridine reductase
Short chain dehydrogenase/reductase family 33C member 1
Gene namesi
Name:QDPR
Synonyms:DHPR, SDR33C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000151552.11.
HGNCiHGNC:9752. QDPR.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Hyperphenylalaninemia, BH4-deficient, C (HPABH4C)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare 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.
See also OMIM:261630
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00812114L → P in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs756639609Ensembl.1
Natural variantiVAR_02176717G → R in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs757483045Ensembl.1
Natural variantiVAR_00812217G → V in HPABH4C; severe. 1 Publication1
Natural variantiVAR_02176818G → D in HPABH4C; severe. 1 Publication1
Natural variantiVAR_00696023G → D in HPABH4C; severe. 3 PublicationsCorresponds to variant dbSNP:rs104893863Ensembl.1
Natural variantiVAR_00696136W → R in HPABH4C. Corresponds to variant dbSNP:rs104893865Ensembl.1
Natural variantiVAR_02176966Q → R in HPABH4C; severe. 1 Publication1
Natural variantiVAR_00696274L → P in HPABH4C. 1
Natural variantiVAR_006963108W → G in HPABH4C. 1 PublicationCorresponds to variant dbSNP:rs104893864Ensembl.1
Natural variantiVAR_006964123T → TT in HPABH4C. 1 Publication1
Natural variantiVAR_006965145P → L in HPABH4C. 1
Natural variantiVAR_021770149G → R in HPABH4C. 1 Publication1
Natural variantiVAR_006966150Y → C in HPABH4C; mild. 2 PublicationsCorresponds to variant dbSNP:rs104893866Ensembl.1
Natural variantiVAR_006967151G → S in HPABH4C; mild. 1
Natural variantiVAR_006968158H → Y in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs750201480Ensembl.1
Natural variantiVAR_006969170G → S in HPABH4C. Corresponds to variant dbSNP:rs769460415Ensembl.1
Natural variantiVAR_006970212F → C in HPABH4C; mild. 1
Natural variantiVAR_006971218G → GITG in HPABH4C; mild. 1

Keywords - Diseasei

Disease mutation, Phenylketonuria

Organism-specific databases

DisGeNETi5860.
MalaCardsiQDPR.
MIMi261630. phenotype.
OpenTargetsiENSG00000151552.
Orphaneti226. Dihydropteridine reductase deficiency.
PharmGKBiPA34094.

Chemistry databases

ChEMBLiCHEMBL3730.
DrugBankiDB03814. 2-(N-Morpholino)-Ethanesulfonic Acid.
DB00157. NADH.

Polymorphism and mutation databases

BioMutaiQDPR.
DMDMi118572639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedND:1 Publication
ChainiPRO_00000546362 – 244Dihydropteridine reductaseAdd BLAST243

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineND:1 Publication1
Modified residuei73N6-succinyllysineHMP:1
Modified residuei79N6-succinyllysineHMP:1
Modified residuei96N6-succinyllysineHMP:1
Modified residuei102N6-succinyllysineHMP:1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP09417.
MaxQBiP09417.
PaxDbiP09417.
PeptideAtlasiP09417.
PRIDEiP09417.

2D gel databases

REPRODUCTION-2DPAGEiIPI00014439.
UCD-2DPAGEiP09417.

PTM databases

iPTMnetiP09417.
PhosphoSitePlusiP09417.

Expressioni

Gene expression databases

BgeeiENSG00000151552.
CleanExiHS_QDPR.
ExpressionAtlasiP09417. baseline and differential.
GenevisibleiP09417. HS.

Organism-specific databases

HPAiHPA058951.
HPA065649.

Interactioni

Subunit structurei

Homodimer.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111798. 26 interactors.
IntActiP09417. 4 interactors.
MINTiMINT-5002411.
STRINGi9606.ENSP00000281243.

Chemistry databases

BindingDBiP09417.

Structurei

Secondary structure

1244
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi11 – 16ND:6
Turni17 – 19ND:3
Helixi21 – 32ND:12
Beta strandi36 – 43ND:8
Beta strandi48 – 53ND:6
Helixi60 – 75ND:16
Beta strandi80 – 85ND:6
Helixi100 – 110ND:11
Helixi112 – 125ND:14
Beta strandi126 – 135ND:10
Helixi138 – 141ND:4
Helixi148 – 165ND:18
Beta strandi176 – 181ND:6
Helixi188 – 191ND:4
Helixi199 – 201ND:3
Helixi205 – 216ND:12
Turni217 – 220ND:4
Beta strandi227 – 233ND:7
Beta strandi236 – 242ND:7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HDRX-ray2.50A1-244[»]
ProteinModelPortaliP09417.
SMRiP09417.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09417.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG4022. Eukaryota.
ENOG4111D6J. LUCA.
GeneTreeiENSGT00390000000470.
HOGENOMiHOG000232194.
HOVERGENiHBG001000.
InParanoidiP09417.
KOiK00357.
OMAiNRKSMPD.
OrthoDBiEOG091G0ILG.
PhylomeDBiP09417.
TreeFamiTF105932.

Family and domain databases

InterProiView protein in InterPro
IPR036291. NAD(P)-bd_dom_sf.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
PfamiView protein in Pfam
PF00106. adh_short. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiView protein in PROSITE
PS00061. ADH_SHORT. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P09417-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAAAAGEA RRVLVYGGRG ALGSRCVQAF RARNWWVASV DVVENEEASA
60 70 80 90 100
SIIVKMTDSF TEQADQVTAE VGKLLGEEKV DAILCVAGGW AGGNAKSKSL
110 120 130 140 150
FKNCDLMWKQ SIWTSTISSH LATKHLKEGG LLTLAGAKAA LDGTPGMIGY
160 170 180 190 200
GMAKGAVHQL CQSLAGKNSG MPPGAAAIAV LPVTLDTPMN RKSMPEADFS
210 220 230 240
SWTPLEFLVE TFHDWITGKN RPSSGSLIQV VTTEGRTELT PAYF
Length:244
Mass (Da):25,790
Last modified:November 28, 2006 - v2
Checksum:i0852F9F0CA38AB1C
GO
Isoform 2 (identifier: P09417-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-66: Missing.

Note: No experimental confirmation available.
Show »
Length:213
Mass (Da):22,408
Checksum:i042BEB8C3F313C20
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00812114L → P in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs756639609Ensembl.1
Natural variantiVAR_02176717G → R in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs757483045Ensembl.1
Natural variantiVAR_00812217G → V in HPABH4C; severe. 1 Publication1
Natural variantiVAR_02176818G → D in HPABH4C; severe. 1 Publication1
Natural variantiVAR_00696023G → D in HPABH4C; severe. 3 PublicationsCorresponds to variant dbSNP:rs104893863Ensembl.1
Natural variantiVAR_00696136W → R in HPABH4C. Corresponds to variant dbSNP:rs104893865Ensembl.1
Natural variantiVAR_01302751S → T3 Publications1
Natural variantiVAR_02176966Q → R in HPABH4C; severe. 1 Publication1
Natural variantiVAR_00696274L → P in HPABH4C. 1
Natural variantiVAR_006963108W → G in HPABH4C. 1 PublicationCorresponds to variant dbSNP:rs104893864Ensembl.1
Natural variantiVAR_006964123T → TT in HPABH4C. 1 Publication1
Natural variantiVAR_006965145P → L in HPABH4C. 1
Natural variantiVAR_021770149G → R in HPABH4C. 1 Publication1
Natural variantiVAR_006966150Y → C in HPABH4C; mild. 2 PublicationsCorresponds to variant dbSNP:rs104893866Ensembl.1
Natural variantiVAR_006967151G → S in HPABH4C; mild. 1
Natural variantiVAR_006968158H → Y in HPABH4C; severe. 1 PublicationCorresponds to variant dbSNP:rs750201480Ensembl.1
Natural variantiVAR_006969170G → S in HPABH4C. Corresponds to variant dbSNP:rs769460415Ensembl.1
Natural variantiVAR_006970212F → C in HPABH4C; mild. 1
Natural variantiVAR_006971218G → GITG in HPABH4C; mild. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05435636 – 66Missing in isoform 2. IBD:Add BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04882 mRNA. Translation: CAA28571.1.
M16447 mRNA. Translation: AAA52305.1.
AJ006239
, AJ006240, AJ006241, AJ006242, AJ006243, AJ006244, AJ006245 Genomic DNA. Translation: CAA06930.1.
AB053170 Genomic DNA. Translation: BAB20429.1.
AK124382 mRNA. Translation: BAG54033.1.
AK289773 mRNA. Translation: BAF82462.1.
AK223437 mRNA. Translation: BAD97157.1.
AC093600 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW92777.1.
CH471069 Genomic DNA. Translation: EAW92778.1.
BC000576 mRNA. Translation: AAH00576.1.
CCDSiCCDS3421.1. [P09417-1]
CCDS77904.1. [P09417-2]
PIRiA93655. RDHUP.
RefSeqiNP_000311.2. NM_000320.2. [P09417-1]
NP_001293069.1. NM_001306140.1. [P09417-2]
UniGeneiHs.75438.

Genome annotation databases

EnsembliENST00000281243; ENSP00000281243; ENSG00000151552. [P09417-1]
ENST00000428702; ENSP00000390944; ENSG00000151552. [P09417-2]
GeneIDi5860.
KEGGihsa:5860.
UCSCiuc003gpd.4. human. [P09417-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDHPR_HUMAN
AccessioniPrimary (citable) accession number: P09417
Secondary accession number(s): A8K158
, B3KW71, Q53F52, Q9H3M5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 28, 2006
Last modified: October 25, 2017
This is version 195 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families