SPR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Z6Z, 4HWK, 4J7U, 4J7X, 4XWY, 4Z3K
Identifiers
Aliases	SPR, SDR38C1, sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase), sepiapterin reductase
External IDs	OMIM: 182125 MGI: 103078 HomoloGene: 37735 GeneCards: SPR
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p13.2 Start 72,887,382 bp[1] End 72,892,158 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 C3|6 37.15 cM Start 85,107,158 bp[2] End 85,114,748 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver right adrenal gland body of pancreas left adrenal gland body of stomach kidney left ventricle islet of Langerhans rectum gastrocnemius muscle Top expressed in ankle joint kidney yolk sac left lobe of liver proximal tubule lip mucous cell of stomach interventricular septum crypt of lieberkuhn of small intestine triceps brachii muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sepiapterin reductase activity aldo-keto reductase (NADP) activity NADP binding oxidoreductase activity Cellular component nucleoplasm extracellular exosome cytoplasm cytosol Biological process nitric oxide biosynthetic process regulation of nitric-oxide synthase activity tetrahydrobiopterin biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6697 20751 Ensembl ENSG00000116096 ENSMUSG00000033735 UniProt P35270 Q64105 RefSeq (mRNA) NM_003124 NM_011467 RefSeq (protein) NP_003115 n/a Location (UCSC) Chr 2: 72.89 – 72.89 Mb Chr 6: 85.11 – 85.11 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene.^[5][6][7]

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases. SPR plays an important role in the biosynthesis of tetrahydrobiopterin.^[7]

Reaction

sepiapterin reductase
Sepiapterin reductase homodimer, Human
Identifiers
EC no.	1.1.1.153
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Sepiapterin reductase (SPR) catalyzes the chemical reaction

L-erythro-7,8-dihydrobiopterin + NADP+ ${\displaystyle \rightleftharpoons }$ sepiapterin + NADPH + H+

Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP⁺, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H⁺).

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP⁺ oxidoreductase. This enzyme participates in folate biosynthesis.

^[8]

Clinical significance

Mutations of the SPR gene may cause sepiapterin reductase deficiency, a rare disease. The clinical phenotype can include progressive psychomotor retardation, altered tone, seizures, choreoathetosis, temperature instability, hypersalivation, microcephaly, and irritability. Patients with sepiapterin reductase deficiency also manifest dystonia with diurnal variation, oculogyric crises, tremor, hypersomnolence, oculomotor apraxia, and weakness.^[9] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).^[10]