Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods
Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase
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SPR is the terminal enzyme in the BH4 biosynthetic pathway
"sepiapterin reductase (SPR), which is a member of the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family and acts as the terminal enzyme in the biosynthetic pathway of tetrahydrobiopterin cofactor (BH4)"
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Ser-158, Tyr-171, and Lys-175 are essential for catalytic activity
"Ser-158, Tyr-171, and Lys-175 contributed to the catalytic activity of SPR, and both Tyr-171 and Ser-158 are simultaneously necessary on proton transfer to the carbonyl functional groups of substrate"
Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia
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SPR mutations cause progressive psychomotor retardation with dystonia and monoamine deficiency
"two patients with progressive psychomotor retardation, dystonia, severe dopamine and serotonin deficiencies (low levels of 5-hydroxyindoleacetic and homovanillic acids), and abnormal pterin pattern"
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SPR deficiency causes BH4-dependent neurotransmitter deficiency without hyperphenylalaninemia
"autosomal recessive SR deficiency leads to BH(4) and to neurotransmitter deficiencies without hyperphenylalaninemia and may not be detected by neonatal screening for phenylketonuria"
Functional tetrahydrobiopterin synthesis in human platelets
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Human platelets have functional de novo BH4 synthesis
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SPR mRNA and enzymatic activity present in freshly isolated platelets
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BH4 is essential cofactor for NO synthase activity
Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis
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First cloning of human SPR cDNA
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261 amino acids, 28,047 Da molecular mass
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74% identity with rat SPR
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Homology to SDR family members
Large-scale proteomics and phosphoproteomics of urinary exosomes
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine
Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors
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Six crystal structures of chemically diverse fragment inhibitors complexed with SPR resolve binding modes in the sepiapterin pocket of the NADP-bound active site
"We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket."
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context
Genomic organization and chromosomal localization of the human sepiapterin reductase gene
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SPR gene has 3 exons spanning ~4 kb
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Located on chromosome 2p13
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SPR catalyzes final step of BH4 biosynthesis
PTHP is reduced to BH4 by sepiapterin reductase (SPR)
Sepiapterin reductase (SPR) is phosphorylated by Ca2+/calmodulin-dependent protein kinase II
Salvage - Sepiapterin is reduced to q-BH2
Deep research report on SPR