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P35270 (SPRE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sepiapterin reductase

Short name=SPR
EC=1.1.1.153
Gene names
Name:SPR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH.

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

Subunit structure

Homodimer.

Subcellular location

Cytoplasm.

Post-translational modification

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

Involvement in disease

Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency (DRDSPRD) [MIM:612716]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.14

Sequence similarities

Belongs to the sepiapterin reductase family.

Biophysicochemical properties

Kinetic parameters:

KM=14.3 µM for sepiapterin Ref.9

KM=10 µM for NADPH

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 261261Sepiapterin reductase
PRO_0000072149

Regions

Nucleotide binding14 – 207NADP
Nucleotide binding42 – 432NADP
Nucleotide binding69 – 702NADP
Nucleotide binding201 – 2066NADP
Region157 – 1582Substrate binding By similarity

Sites

Binding site1701Substrate By similarity
Binding site1741NADP By similarity
Binding site1991Substrate; via amide nitrogen By similarity
Binding site2571Substrate By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue2131Phosphoserine; by CaMK2; in vitro Ref.9

Natural variations

Natural variant1501R → G in DRDSPRD. Ref.12 Ref.14
VAR_058007
Natural variant1631P → L in DRDSPRD. Ref.13
VAR_058008

Experimental info

Mutagenesis2131S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters. Ref.9
Sequence conflict101C → R in BAD96662. Ref.4

Secondary structure

........................................ 261
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P35270 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 9C9BF76212826F47

FASTA26128,048
        10         20         30         40         50         60 
MEGGLGRAVC LLTGASRGFG RTLAPLLASL LSPGSVLVLS ARNDEALRQL EAELGAERSG 

        70         80         90        100        110        120 
LRVVRVPADL GAEAGLQQLL GALRELPRPK GLQRLLLINN AGSLGDVSKG FVDLSDSTQV 

       130        140        150        160        170        180 
NNYWALNLTS MLCLTSSVLK AFPDSPGLNR TVVNISSLCA LQPFKGWALY CAGKAARDML 

       190        200        210        220        230        240 
FQVLALEEPN VRVLNYAPGP LDTDMQQLAR ETSVDPDMRK GLQELKAKGK LVDCKVSAQK 

       250        260 
LLSLLEKDEF KSGAHVDFYD K 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequencing of cDNA encoding human sepiapterin reductase -- an enzyme involved in tetrahydrobiopterin biosynthesis."
Ichinose H., Katoh S., Sueoka T., Titani K., Fujita K., Nagatsu T.
Biochem. Biophys. Res. Commun. 179:183-189(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species."
Maier J., Schott K., Werner T., Bacher A., Ziegler I.
Exp. Cell Res. 204:217-222(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Salivary gland.
[4]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[8]"Genomic organization and chromosomal localization of the human sepiapterin reductase gene."
Ohye T., Hori T.A., Katoh S., Nagatsu T., Ichinose H.
Biochem. Biophys. Res. Commun. 251:597-602(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]"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-213, MUTAGENESIS OF SER-213.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structure of human sepiapterin reductase."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 5-261 IN COMPLEX WITH NADP.
[12]"Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia."
Bonafe L., Thony B., Penzien J.M., Czarnecki B., Blau N.
Am. J. Hum. Genet. 69:269-277(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DRDSPRD GLY-150.
[13]"Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia."
Abeling N.G.G.M., Duran M., Bakker H.D., Stroomer L., Thoeny B., Blau N., Booij J., Poll-The B.T.
Mol. Genet. Metab. 89:116-120(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DRDSPRD LEU-163.
[14]"Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency."
Friedman J., Hyland K., Blau N., MacCollin M.
Neurology 67:2032-2035(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DRDSPRD GLY-150.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJQ1176.
RefSeqNP_003115.1. NM_003124.4.
UniGeneHs.301540.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP35270.
SMRP35270. Positions 4-260.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112575. 14 interactions.
IntActP35270. 1 interaction.
MINTMINT-3304575.
STRING9606.ENSP00000234454.

PTM databases

PhosphoSiteP35270.

Polymorphism databases

DMDM464801.

Proteomic databases

PaxDbP35270.
PeptideAtlasP35270.
PRIDEP35270.

Protocols and materials databases

DNASU6697.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000234454; ENSP00000234454; ENSG00000116096.
GeneID6697.
KEGGhsa:6697.
UCSCuc002sik.2. human.

Organism-specific databases

CTD6697.
GeneCardsGC02P073026.
HGNCHGNC:11257. SPR.
HPAHPA039505.
MIM182125. gene.
612716. phenotype.
neXtProtNX_P35270.
Orphanet70594. Dopa-responsive dystonia due to sepiapterin reductase deficiency.
PharmGKBPA36087.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1028.
HOVERGENHBG006973.
InParanoidP35270.
KOK00072.
OMANSNCIFH.
OrthoDBEOG7327PS.
PhylomeDBP35270.
TreeFamTF326358.

Enzyme and pathway databases

BioCycMetaCyc:HS03979-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP35270.
BgeeP35270.
CleanExHS_SPR.
GenevestigatorP35270.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR006393. Sepiapterin_red.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSPR00081. GDHRDH.
TIGRFAMsTIGR01500. sepiapter_red. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSPR. human.
EvolutionaryTraceP35270.
GeneWikiSepiapterin_reductase.
GenomeRNAi6697.
NextBio26111.
PROP35270.
SOURCESearch...

Entry information

Entry nameSPRE_HUMAN
AccessionPrimary (citable) accession number: P35270
Secondary accession number(s): A8K741 expand/collapse secondary AC list , D6W5H2, Q53GI9, Q9UBB1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM