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Reviewed, UniProtKB/Swiss-Prot P35270 (SPRE_HUMAN)

Last modified June 16, 2009. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Sepiapterin reductase
      Short name=SPR
    EC=1.1.1.153
Gene names
Name: SPR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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

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

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

Depressed synthesis of tetrahydrobiopterin may play a role in a variety of human diseases.

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

Ontologies

Keywords
   Cellular componentCytoplasm
   LigandNADP
   Molecular functionOxidoreductase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological processnitric oxide biosynthetic process

Inferred from direct assay. Source: UniProtKB

oxidation reduction Ref.1

Traceable author statement. Source: UniProtKB

tetrahydrobiopterin biosynthetic process Ref.1

Traceable author statement. Source: UniProtKB

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionNADP or NADPH binding Ref.1

Traceable author statement. Source: UniProtKB

aldo-keto reductase activity Ref.1

Traceable author statement. Source: UniProtKB

sepiapterin reductase activity Ref.8

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 261261Sepiapterin reductase
PRO_0000072149

Regions

Nucleotide binding13 – 3927NADP By similarity
Region28 – 325Pterin binding By similarity

Amino acid modifications

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

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
P35270-1 [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: 1883349] [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: 8440319] [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: 14702039] [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: 15815621] [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: 15489334] [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: 9792819] [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: 11825621] [Abstract]
Cited for: KINETIC PARAMETERS, PHOSPHORYLATION AT SER-213, MUTAGENESIS OF SER-213.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

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.
BC017310 mRNA. Translation: AAH17310.1.
AB017547 Genomic DNA. Translation: BAA34534.1.
IPIIPI00017469.
PIRJQ1176.
RefSeqNP_003115.1.
UniGeneHs.301540

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1Z6ZX-ray2.50A/B/C/D/E/F5-261[»]
ModBaseSearch...

PTM databases

PhosphoSiteP35270.

Proteomic databases

PeptideAtlasP35270.
PRIDEP35270.

Genome annotation databases

EnsemblENSG00000116096. Homo sapiens. [Contig view]
GeneID6697.
KEGGhsa:6697.
NMPDRfig|9606.3.peg.18026.

Organism-specific databases

GeneCardsGC02P073026.
H-InvDBHIX0002155.
HGNCHGNC:11257. SPR.
MIM182125. gene+phenotype.
Orphanet70594. Motor and cognitive disorder due to sepiapterin reductase deficiency.
PharmGKBPA36087.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP35270.
HOVERGENP35270.
OMAP35270. SVDPDMR.

Enzyme and pathway databases

BioCycMetaCyc:MON-13412.
BRENDA1.1.1.153. 247.

Gene expression databases

ArrayExpressP35270.
BgeeP35270.
CleanExHS_SPR.
GermOnlineENSG00000116096. Homo sapiens.

Family and domain databases

InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR006393. Sepiapterin_red.
[Graphical view]
Gene3DG3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PANTHERPTHR19410. ADH_short_C2. 1 hit.
PfamPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSPR00081. GDHRDH.
TIGRFAMsTIGR01500. sepiapter_red. 1 hit.
ProtoNetSearch...

Other Resources

NextBio26111.
SOURCESearch...

Entry information

Entry nameSPRE_HUMAN
AccessionPrimary (citable) accession number: P35270
Secondary accession number(s): A8K741, Q53GI9, Q9UBB1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: June 16, 2009
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents