Sepiapterin reductase

Mammalian protein found in Homo sapiens
SPR
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1Z6Z, 4HWK, 4J7U, 4J7X, 4XWY, 4Z3K

Identifiers
AliasesSPR, SDR38C1, sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase), sepiapterin reductase
External IDsOMIM: 182125 MGI: 103078 HomoloGene: 37735 GeneCards: SPR
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for SPR
Genomic location for SPR
Band2p13.2Start72,887,382 bp[1]
End72,892,158 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for SPR
Genomic location for SPR
Band6 C3|6 37.15 cMStart85,107,158 bp[2]
End85,114,748 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 6: 85.11 – 85.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000116096 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033735 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (Oct 1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochem Biophys Res Commun. 179 (1): 183–189. doi:10.1016/0006-291X(91)91352-D. PMID 1883349.
  6. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact. 178 (1–3): 94–98. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  7. ^ a b "Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)".
  8. ^ "BRENDA - Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)".
  9. ^ Pearl PL, Taylor JL, Trzcinski S, Sokohl A (May 2007). "The pediatric neurotransmitter disorders". J Child Neurol. 22 (5): 606–616. doi:10.1177/0883073807302619. PMID 17690069. S2CID 10689202.
  10. ^ "Patient registry".

Further reading

  • Katoh S (1971). "Sepiapterin Reductase from Horse Liver: Purification and Properties of the Enzyme". Arch. Biochem. Biophys. 146 (1): 202–214. doi:10.1016/S0003-9861(71)80057-7. PMID 4401291.
  • Matsubara M, Katoh S, Akino M, Kaufman S (1966). "Sepiapterin Reductase". Biochim. Biophys. Acta. 122 (2): 202–212. doi:10.1016/0926-6593(66)90062-2. PMID 5969298.
  • Takikawa S, Curtius HC, Redweik U, Leimbacher W, Ghisla S (1987). "Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver". Eur. J. Biochem. 161 (2): 295–302. doi:10.1111/j.1432-1033.1986.tb10446.x. PMID 3536512.
  • Thöny B, Heizmann CW, Mattei MG (1995). "Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization". Genomics. 26 (1): 168–170. doi:10.1016/0888-7543(95)80101-Q. PMID 7782081.
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Maier J, Schott K, Werner T, Bacher A, Ziegler I (1993). "Northern Blot Analysis of Sepiapterin Reductase mRNA in Mammalian Cell Lines and Tissues". Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology. Vol. 338. pp. 195–8. doi:10.1007/978-1-4615-2960-6_39. ISBN 978-1-4613-6287-6. PMID 8304109.
  • Maier J, Schott K, Werner T, Bacher A, Ziegler I (1993). "Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species". Exp. Cell Res. 204 (2): 217–222. doi:10.1006/excr.1993.1027. PMID 8440319.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Blau N, Thöny B, Renneberg A, Arnold LA, Hyland K (1998). "Dihydropteridine reductase deficiency localized to the central nervous system". J. Inherit. Metab. Dis. 21 (4): 433–434. doi:10.1023/A:1005327313348. PMID 9700606. S2CID 20969872.
  • Ohye T, Hori TA, Katoh S, Nagatsu T, Ichinose H (1998). "Genomic organization and chromosomal localization of the human sepiapterin reductase gene". Biochem. Biophys. Res. Commun. 251 (2): 597–602. doi:10.1006/bbrc.1998.9503. PMID 9792819.
  • Blau N, Thöny B, Renneberg A, Penzien JM, Hyland K, Hoffmann GF (1999). "Variant of dihydropteridine reductase deficiency without hyperphenylalaninaemia: effect of oral phenylalanine loading". J. Inherit. Metab. Dis. 22 (3): 216–220. doi:10.1023/A:1005584627797. PMID 10384371. S2CID 30670124.
  • Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N (2001). "Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia". Am. J. Hum. Genet. 69 (2): 269–277. doi:10.1086/321970. PMC 1235302. PMID 11443547.
  • Fujimoto K, Takahashi SY, Katoh S (2002). "Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II". Biochim. Biophys. Acta. 1594 (1): 191–8. doi:10.1016/S0167-4838(01)00300-4. PMID 11825621.
  • Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Franscini N, Bachli EB, Blau N, Fischler M, Walter RB, Schaffner A, et al. (2005). "Functional tetrahydrobiopterin synthesis in human platelets". Circulation. 110 (2): 186–192. doi:10.1161/01.CIR.0000134281.82972.57. PMID 15197144.
  • Steinberger D, Blau N, Goriuonov D, Bitsch J, Zuker M, Hummel S, et al. (2005). "Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene (SPR) in a patient with dopa-responsive dystonia". Neurogenetics. 5 (3): 187–190. doi:10.1007/s10048-004-0182-3. PMID 15241655. S2CID 4833737.
  • Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Sharma M, Mueller JC, Zimprich A, Lichtner P, Hofer A, Leitner P, et al. (2006). "The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations". J. Med. Genet. 43 (7): 557–562. doi:10.1136/jmg.2005.039149. PMC 2593029. PMID 16443856.
  • Farrugia R, Scerri CA, Montalto SA, Parascandolo R, Neville BG, Felice AE (2007). "Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population". Mol. Genet. Metab. 90 (3): 277–283. doi:10.1016/j.ymgme.2006.10.013. PMID 17188538.
  • Tobin JE, Cui J, Wilk JB, Latourelle J, Laramie J, McKee A, et al. (2007). "Sepiapterin reductase expression is increased in Parkinson's disease brain tissue". Brain Res. 1139: 42–47. doi:10.1016/j.brainres.2007.01.001. PMC 1868471. PMID 17270157.

External links

  • Overview of all the structural information available in the PDB for UniProt: P35270 (Human Sepiapterin reductase) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q64105 (Mouse Sepiapterin reductase) at the PDBe-KB.
  • v
  • t
  • e
  • 1z6z: Crystal Structure of Human Sepiapterin Reductase in complex with NADP+
    1z6z: Crystal Structure of Human Sepiapterin Reductase in complex with NADP+
Portal:
  • icon Biology
  • v
  • t
  • e
Metabolism of vitamins, coenzymes, and cofactors
Fat soluble vitamins
Vitamin A
Vitamin E
Vitamin D
  • liver (Sterol 27-hydroxylase or CYP27A1)
  • renal (25-Hydroxyvitamin D3 1-alpha-hydroxylase or CYP27B1)
  • degradation (1,25-Dihydroxyvitamin D3 24-hydroxylase or CYP24A1)
Vitamin K
Water soluble vitamins
Thiamine (B1)
Niacin (B3)
Pantothenic acid (B5)
Folic acid (B9)
Vitamin B12
Vitamin C
Riboflavin (B2)
Nonvitamin cofactors
Tetrahydrobiopterin
Molybdopterin