Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Sepiapterin reductase

Gene

SPR

Organism
Homo sapiens (Human)
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=14.3 µM for sepiapterin1 Publication
  2. KM=10 µM for NADPH1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei170SubstrateBy similarity1
    Binding sitei174NADPBy similarity1
    Binding sitei199Substrate; via amide nitrogenBy similarity1
    Binding sitei257SubstrateBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi14 – 20NADP1 Publication7
    Nucleotide bindingi42 – 43NADP1 Publication2
    Nucleotide bindingi69 – 70NADP1 Publication2
    Nucleotide bindingi201 – 206NADP1 Publication6

    GO - Molecular functioni

    • aldo-keto reductase (NADP) activity Source: UniProtKB
    • NADP binding Source: UniProtKB
    • sepiapterin reductase activity Source: UniProtKB

    GO - Biological processi

    • nitric oxide biosynthetic process Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • regulation of nitric-oxide synthase activity Source: Reactome
    • tetrahydrobiopterin biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03979-MONOMER.
    ZFISH:HS03979-MONOMER.
    ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SIGNORiP35270.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sepiapterin reductase (EC:1.1.1.153)
    Short name:
    SPR
    Gene namesi
    Name:SPR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:11257. SPR.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • nucleoplasm Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency (DRDSPRD)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of DOPA-responsive dystonia. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.
    See also OMIM:612716
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_058007150R → G in DRDSPRD. 2 PublicationsCorresponds to variant rs104893665dbSNPEnsembl.1
    Natural variantiVAR_058008163P → L in DRDSPRD. 1 PublicationCorresponds to variant rs104893666dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi213S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Dystonia

    Organism-specific databases

    DisGeNETi6697.
    MalaCardsiSPR.
    MIMi612716. phenotype.
    OpenTargetsiENSG00000116096.
    Orphaneti70594. Dopa-responsive dystonia due to sepiapterin reductase deficiency.
    PharmGKBiPA36087.

    Polymorphism and mutation databases

    BioMutaiSPR.
    DMDMi464801.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000721491 – 261Sepiapterin reductaseAdd BLAST261

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineBy similarity1
    Modified residuei32PhosphoserineBy similarity1
    Modified residuei103PhosphoserineCombined sources1
    Modified residuei213Phosphoserine; by CaMK2; in vitro1 Publication1

    Post-translational modificationi

    In vitro phosphorylation of Ser-213 by CaMK2 does not change kinetic parameters.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP35270.
    MaxQBiP35270.
    PaxDbiP35270.
    PeptideAtlasiP35270.
    PRIDEiP35270.

    PTM databases

    iPTMnetiP35270.
    PhosphoSitePlusiP35270.

    Expressioni

    Gene expression databases

    BgeeiENSG00000116096.
    CleanExiHS_SPR.
    GenevisibleiP35270. HS.

    Organism-specific databases

    HPAiHPA039505.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi112575. 48 interactors.
    IntActiP35270. 1 interactor.
    MINTiMINT-3304575.
    STRINGi9606.ENSP00000234454.

    Structurei

    Secondary structure

    1261
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi6 – 14Combined sources9
    Helixi18 – 28Combined sources11
    Beta strandi36 – 42Combined sources7
    Helixi44 – 54Combined sources11
    Helixi56 – 59Combined sources4
    Beta strandi62 – 67Combined sources6
    Helixi73 – 85Combined sources13
    Beta strandi94 – 99Combined sources6
    Helixi111 – 113Combined sources3
    Helixi117 – 127Combined sources11
    Helixi129 – 141Combined sources13
    Beta strandi149 – 155Combined sources7
    Helixi158 – 160Combined sources3
    Helixi168 – 187Combined sources20
    Beta strandi191 – 197Combined sources7
    Beta strandi200 – 203Combined sources4
    Helixi204 – 212Combined sources9
    Helixi216 – 227Combined sources12
    Helixi234 – 247Combined sources14
    Beta strandi254 – 257Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Z6ZX-ray2.50A/B/C/D/E/F5-261[»]
    4HWKX-ray2.40A/B/C/D1-261[»]
    4J7UX-ray2.44A/B/C/D1-261[»]
    4J7XX-ray2.60A/B/F/J1-261[»]
    4XWYX-ray2.35A/B/C/D1-261[»]
    4Z3KX-ray2.35A/B/C/D1-261[»]
    ProteinModelPortaliP35270.
    SMRiP35270.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP35270.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni157 – 158Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the sepiapterin reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1204. Eukaryota.
    ENOG4111PZG. LUCA.
    GeneTreeiENSGT00440000033609.
    HOVERGENiHBG006973.
    InParanoidiP35270.
    KOiK00072.
    OMAiVDCKVSA.
    OrthoDBiEOG091G0N30.
    PhylomeDBiP35270.
    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.

    P35270-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEGGLGRAVC LLTGASRGFG RTLAPLLASL LSPGSVLVLS ARNDEALRQL
    60 70 80 90 100
    EAELGAERSG LRVVRVPADL GAEAGLQQLL GALRELPRPK GLQRLLLINN
    110 120 130 140 150
    AGSLGDVSKG FVDLSDSTQV NNYWALNLTS MLCLTSSVLK AFPDSPGLNR
    160 170 180 190 200
    TVVNISSLCA LQPFKGWALY CAGKAARDML FQVLALEEPN VRVLNYAPGP
    210 220 230 240 250
    LDTDMQQLAR ETSVDPDMRK GLQELKAKGK LVDCKVSAQK LLSLLEKDEF
    260
    KSGAHVDFYD K
    Length:261
    Mass (Da):28,048
    Last modified:February 1, 1994 - v1
    Checksum:i9C9BF76212826F47
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti10C → R in BAD96662 (Ref. 4) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_058007150R → G in DRDSPRD. 2 PublicationsCorresponds to variant rs104893665dbSNPEnsembl.1
    Natural variantiVAR_058008163P → L in DRDSPRD. 1 PublicationCorresponds to variant rs104893666dbSNPEnsembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M76231 mRNA. Translation: AAA60314.1.
    AK291856 mRNA. Translation: BAF84545.1.
    AK222942 mRNA. Translation: BAD96662.1.
    AC092630 Genomic DNA. Translation: AAY15035.1.
    CH471053 Genomic DNA. Translation: EAW99757.1.
    CH471053 Genomic DNA. Translation: EAW99758.1.
    BC017310 mRNA. Translation: AAH17310.1.
    AB017547 Genomic DNA. Translation: BAA34534.1.
    CCDSiCCDS1920.1.
    PIRiJQ1176.
    RefSeqiNP_003115.1. NM_003124.4.
    UniGeneiHs.301540.

    Genome annotation databases

    EnsembliENST00000234454; ENSP00000234454; ENSG00000116096.
    GeneIDi6697.
    KEGGihsa:6697.
    UCSCiuc002sik.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M76231 mRNA. Translation: AAA60314.1.
    AK291856 mRNA. Translation: BAF84545.1.
    AK222942 mRNA. Translation: BAD96662.1.
    AC092630 Genomic DNA. Translation: AAY15035.1.
    CH471053 Genomic DNA. Translation: EAW99757.1.
    CH471053 Genomic DNA. Translation: EAW99758.1.
    BC017310 mRNA. Translation: AAH17310.1.
    AB017547 Genomic DNA. Translation: BAA34534.1.
    CCDSiCCDS1920.1.
    PIRiJQ1176.
    RefSeqiNP_003115.1. NM_003124.4.
    UniGeneiHs.301540.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Z6ZX-ray2.50A/B/C/D/E/F5-261[»]
    4HWKX-ray2.40A/B/C/D1-261[»]
    4J7UX-ray2.44A/B/C/D1-261[»]
    4J7XX-ray2.60A/B/F/J1-261[»]
    4XWYX-ray2.35A/B/C/D1-261[»]
    4Z3KX-ray2.35A/B/C/D1-261[»]
    ProteinModelPortaliP35270.
    SMRiP35270.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112575. 48 interactors.
    IntActiP35270. 1 interactor.
    MINTiMINT-3304575.
    STRINGi9606.ENSP00000234454.

    PTM databases

    iPTMnetiP35270.
    PhosphoSitePlusiP35270.

    Polymorphism and mutation databases

    BioMutaiSPR.
    DMDMi464801.

    Proteomic databases

    EPDiP35270.
    MaxQBiP35270.
    PaxDbiP35270.
    PeptideAtlasiP35270.
    PRIDEiP35270.

    Protocols and materials databases

    DNASUi6697.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000234454; ENSP00000234454; ENSG00000116096.
    GeneIDi6697.
    KEGGihsa:6697.
    UCSCiuc002sik.3. human.

    Organism-specific databases

    CTDi6697.
    DisGeNETi6697.
    GeneCardsiSPR.
    HGNCiHGNC:11257. SPR.
    HPAiHPA039505.
    MalaCardsiSPR.
    MIMi182125. gene.
    612716. phenotype.
    neXtProtiNX_P35270.
    OpenTargetsiENSG00000116096.
    Orphaneti70594. Dopa-responsive dystonia due to sepiapterin reductase deficiency.
    PharmGKBiPA36087.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1204. Eukaryota.
    ENOG4111PZG. LUCA.
    GeneTreeiENSGT00440000033609.
    HOVERGENiHBG006973.
    InParanoidiP35270.
    KOiK00072.
    OMAiVDCKVSA.
    OrthoDBiEOG091G0N30.
    PhylomeDBiP35270.
    TreeFamiTF326358.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03979-MONOMER.
    ZFISH:HS03979-MONOMER.
    ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SIGNORiP35270.

    Miscellaneous databases

    ChiTaRSiSPR. human.
    EvolutionaryTraceiP35270.
    GeneWikiiSepiapterin_reductase.
    GenomeRNAii6697.
    PROiP35270.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000116096.
    CleanExiHS_SPR.
    GenevisibleiP35270. HS.

    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...

    Entry informationi

    Entry nameiSPRE_HUMAN
    AccessioniPrimary (citable) accession number: P35270
    Secondary accession number(s): A8K741
    , D6W5H2, Q53GI9, Q9UBB1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: November 2, 2016
    This is version 175 of the entry and version 1 of the sequence. [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, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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

    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.