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Protein

Sepiapterin reductase

Gene

Spr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.

Catalytic activityi

L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH.
L-erythro-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH.

Kineticsi

  1. KM=12.6 µM for sepiapterin1 Publication
  2. KM=2.8 µM for NADPH1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei171 – 1711SubstrateBy similarity
    Binding sitei175 – 1751NADPBy similarity
    Binding sitei200 – 2001Substrate; via amide nitrogenBy similarity
    Binding sitei258 – 2581SubstrateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi15 – 217NADPBy similarity
    Nucleotide bindingi43 – 442NADPBy similarity
    Nucleotide bindingi70 – 712NADPBy similarity
    Nucleotide bindingi202 – 2076NADPBy similarity

    GO - Molecular functioni

    • sepiapterin reductase activity Source: UniProtKB

    GO - Biological processi

    • response to organic substance Source: RGD
    • tetrahydrobiopterin biosynthetic process Source: RGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    ReactomeiR-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SABIO-RKP18297.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sepiapterin reductase (EC:1.1.1.153)
    Short name:
    SPR
    Gene namesi
    Name:Spr
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 4

    Organism-specific databases

    RGDi3753. Spr.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi29 – 291A → V: Reduces affinity for NADP and for sepiapterin 4-fold. 1 Publication
    Mutagenesisi46 – 461S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-196 and A-214. 1 Publication
    Mutagenesisi158 – 1581S → D: Reduces activity 4-fold. Loss of activity; when associated with V-171. 1 Publication
    Mutagenesisi171 – 1711Y → V: Reduces activity 4-fold. Loss of activity; when associated with V-171. 1 Publication
    Mutagenesisi175 – 1751K → I: Reduces activity 4-fold. 1 Publication
    Mutagenesisi196 – 1961S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-46 and A-214. 1 Publication
    Mutagenesisi214 – 2141S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-46 and A-196. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 262262Sepiapterin reductasePRO_0000072151Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei33 – 331PhosphoserineCombined sources
    Modified residuei46 – 461Phosphoserine; by CaMK2; in vitro1 Publication
    Modified residuei196 – 1961Phosphoserine; by CaMK2; in vitro1 Publication
    Modified residuei214 – 2141Phosphoserine; by CaMK2; in vitro1 Publication

    Post-translational modificationi

    In vitro phosphorylation of Ser-46, Ser-196 and Ser-214 by CaMK2 does not change kinetic parameters.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP18297.
    PRIDEiP18297.

    PTM databases

    iPTMnetiP18297.
    PhosphoSiteiP18297.

    Expressioni

    Gene expression databases

    ExpressionAtlasiP18297. baseline and differential.
    GenevisibleiP18297. RN.

    Interactioni

    Subunit structurei

    Homodimer.

    Protein-protein interaction databases

    MINTiMINT-4572098.
    STRINGi10116.ENSRNOP00000020749.

    Structurei

    3D structure databases

    ProteinModelPortaliP18297.
    SMRiP18297. Positions 6-261.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni158 – 1592Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the sepiapterin reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1204. Eukaryota.
    ENOG4111PZG. LUCA.
    GeneTreeiENSGT00440000033609.
    HOVERGENiHBG006973.
    InParanoidiP18297.
    KOiK00072.
    OMAiVDCKVSA.
    OrthoDBiEOG7327PS.
    PhylomeDBiP18297.
    TreeFamiTF326358.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR002347. SDR_fam.
    IPR006393. Sepiapterin_red.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PfamiPF00106. adh_short. 1 hit.
    [Graphical view]
    PRINTSiPR00081. GDHRDH.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    TIGRFAMsiTIGR01500. sepiapter_red. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P18297-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEGGRLGCAV CVLTGASRGF GRALAPQLAG LLSPGSVLLL SARSDSMLRQ
    60 70 80 90 100
    LKEELCTQQP GLQVVLAAAD LGTESGVQQL LSAVRELPRP ERLQRLLLIN
    110 120 130 140 150
    NAGTLGDVSK GFLNINDLAE VNNYWALNLT SMLCLTTGTL NAFSNSPGLS
    160 170 180 190 200
    KTVVNISSLC ALQPFKGWGL YCAGKAARDM LYQVLAVEEP SVRVLSYAPG
    210 220 230 240 250
    PLDTNMQQLA RETSMDPELR SRLQKLNSEG ELVDCGTSAQ KLLSLLQRDT
    260
    FQSGAHVDFY DI
    Length:262
    Mass (Da):28,128
    Last modified:November 1, 1990 - v1
    Checksum:iEC992564A0334C61
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M36410 mRNA. Translation: AAA42130.1.
    PIRiA36024.
    RefSeqiNP_062054.1. NM_019181.1.
    UniGeneiRn.6658.

    Genome annotation databases

    EnsembliENSRNOT00000020749; ENSRNOP00000020749; ENSRNOG00000015455.
    GeneIDi29270.
    KEGGirno:29270.
    UCSCiRGD:3753. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M36410 mRNA. Translation: AAA42130.1.
    PIRiA36024.
    RefSeqiNP_062054.1. NM_019181.1.
    UniGeneiRn.6658.

    3D structure databases

    ProteinModelPortaliP18297.
    SMRiP18297. Positions 6-261.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    MINTiMINT-4572098.
    STRINGi10116.ENSRNOP00000020749.

    PTM databases

    iPTMnetiP18297.
    PhosphoSiteiP18297.

    Proteomic databases

    PaxDbiP18297.
    PRIDEiP18297.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000020749; ENSRNOP00000020749; ENSRNOG00000015455.
    GeneIDi29270.
    KEGGirno:29270.
    UCSCiRGD:3753. rat.

    Organism-specific databases

    CTDi6697.
    RGDi3753. Spr.

    Phylogenomic databases

    eggNOGiKOG1204. Eukaryota.
    ENOG4111PZG. LUCA.
    GeneTreeiENSGT00440000033609.
    HOVERGENiHBG006973.
    InParanoidiP18297.
    KOiK00072.
    OMAiVDCKVSA.
    OrthoDBiEOG7327PS.
    PhylomeDBiP18297.
    TreeFamiTF326358.

    Enzyme and pathway databases

    ReactomeiR-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SABIO-RKP18297.

    Miscellaneous databases

    NextBioi608616.
    PROiP18297.

    Gene expression databases

    ExpressionAtlasiP18297. baseline and differential.
    GenevisibleiP18297. RN.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR002347. SDR_fam.
    IPR006393. Sepiapterin_red.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PfamiPF00106. adh_short. 1 hit.
    [Graphical view]
    PRINTSiPR00081. GDHRDH.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    TIGRFAMsiTIGR01500. sepiapter_red. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "The complete amino acid sequence of the mature form of rat sepiapterin reductase."
      Oyama R., Katoh S., Sueoka T., Suzuki M., Ichinose H., Nagatsu T., Titani K.
      Biochem. Biophys. Res. Commun. 173:627-631(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE, ACETYLATION AT MET-1.
    3. "Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase."
      Fujimoto K., Ichinose H., Nagatsu T., Nonaka T., Mitsui Y., Katoh S.
      Biochim. Biophys. Acta 1431:306-314(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ALA-29; SER-158; TYR-171 AND LYS-175.
    4. "Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II."
      Fujimoto K., Takahashi S.Y., Katoh S.
      Biochim. Biophys. Acta 1594:191-198(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: KINETIC PARAMETERS, PHOSPHORYLATION AT SER-46; SER-196 AND SER-214, MUTAGENESIS OF SER-46; SER-196 AND SER-214.
    5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
      Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
      Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiSPRE_RAT
    AccessioniPrimary (citable) accession number: P18297
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: November 1, 1990
    Last modified: April 13, 2016
    This is version 123 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.