SPRE_HUMAN
ID SPRE_HUMAN Reviewed; 261 AA.
AC P35270; A8K741; D6W5H2; Q53GI9; Q9UBB1;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Sepiapterin reductase;
DE Short=SPR;
DE EC=1.1.1.153 {ECO:0000269|PubMed:10350607, ECO:0000269|PubMed:11443547};
GN Name=SPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1883349; DOI=10.1016/0006-291x(91)91352-d;
RA Ichinose H., Katoh S., Sueoka T., Titani K., Fujita K., Nagatsu T.;
RT "Cloning and sequencing of cDNA encoding human sepiapterin reductase -- an
RT enzyme involved in tetrahydrobiopterin biosynthesis.";
RL Biochem. Biophys. Res. Commun. 179:183-189(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8440319; DOI=10.1006/excr.1993.1027;
RA Maier J., Schott K., Werner T., Bacher A., Ziegler I.;
RT "Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various
RT cells and tissues of various species.";
RL Exp. Cell Res. 204:217-222(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9792819; DOI=10.1006/bbrc.1998.9503;
RA Ohye T., Hori T.A., Katoh S., Nagatsu T., Ichinose H.;
RT "Genomic organization and chromosomal localization of the human sepiapterin
RT reductase gene.";
RL Biochem. Biophys. Res. Commun. 251:597-602(1998).
RN [9]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10350607; DOI=10.1016/s0167-4838(99)00054-0;
RA Fujimoto K., Ichinose H., Nagatsu T., Nonaka T., Mitsui Y., Katoh S.;
RT "Functionally important residues tyrosine-171 and serine-158 in sepiapterin
RT reductase.";
RL Biochim. Biophys. Acta 1431:306-314(1999).
RN [10]
RP KINETIC PARAMETERS, PHOSPHORYLATION AT SER-213, AND MUTAGENESIS OF SER-213.
RX PubMed=11825621; DOI=10.1016/s0167-4838(01)00300-4;
RA Fujimoto K., Takahashi S.Y., Katoh S.;
RT "Mutational analysis of sites in sepiapterin reductase phosphorylated by
RT Ca2+/calmodulin-dependent protein kinase II.";
RL Biochim. Biophys. Acta 1594:191-198(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 5-261 IN COMPLEX WITH NADP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human sepiapterin reductase.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [15]
RP VARIANTS DRDSPRD 119-GLN--LYS-261 DEL AND GLY-150, AND CHARACTERIZATION OF
RP VARIANT DRDSPRD GLY-150.
RX PubMed=11443547; DOI=10.1086/321970;
RA Bonafe L., Thony B., Penzien J.M., Czarnecki B., Blau N.;
RT "Mutations in the sepiapterin reductase gene cause a novel
RT tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without
RT hyperphenylalaninemia.";
RL Am. J. Hum. Genet. 69:269-277(2001).
RN [16]
RP VARIANT DRDSPRD LEU-163.
RX PubMed=16650784; DOI=10.1016/j.ymgme.2006.03.010;
RA Abeling N.G.G.M., Duran M., Bakker H.D., Stroomer L., Thoeny B., Blau N.,
RA Booij J., Poll-The B.T.;
RT "Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive
RT dystonia.";
RL Mol. Genet. Metab. 89:116-120(2006).
RN [17]
RP VARIANT DRDSPRD GLY-150.
RX PubMed=17159114; DOI=10.1212/01.wnl.0000247274.21261.b4;
RA Friedman J., Hyland K., Blau N., MacCollin M.;
RT "Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin
RT reductase deficiency.";
RL Neurology 67:2032-2035(2006).
CC -!- FUNCTION: Catalyzes the final one or two reductions in tetra-
CC hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-erythro-7,8-dihydrobiopterin + NADP(+) = H(+) + NADPH +
CC sepiapterin; Xref=Rhea:RHEA:18953, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16095, ChEBI:CHEBI:43029, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.1.1.153;
CC Evidence={ECO:0000269|PubMed:10350607, ECO:0000269|PubMed:11443547};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18955;
CC Evidence={ECO:0000269|PubMed:10350607, ECO:0000269|PubMed:11443547};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = 6-
CC pyruvoyl-5,6,7,8-tetrahydropterin + 2 H(+) + 2 NADPH;
CC Xref=Rhea:RHEA:32627, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:59560, ChEBI:CHEBI:136564;
CC EC=1.1.1.153; Evidence={ECO:0000305|PubMed:10350607};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32629;
CC Evidence={ECO:0000305|PubMed:10350607};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.3 uM for sepiapterin {ECO:0000269|PubMed:10350607,
CC ECO:0000269|PubMed:11825621};
CC KM=10 uM for NADPH {ECO:0000269|PubMed:10350607,
CC ECO:0000269|PubMed:11825621};
CC Note=kcat is 1.1 sec(-1) with sepiapterin as substrate
CC (PubMed:10350607). kcat is 1.1 sec(-1) with NADPH as substrate
CC (PubMed:10350607). {ECO:0000269|PubMed:10350607};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.14}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: In vitro phosphorylation of Ser-213 by CaMK2 does not change
CC kinetic parameters. {ECO:0000269|PubMed:11825621}.
CC -!- DISEASE: Dystonia, DOPA-responsive, due to sepiapterin reductase
CC deficiency (DRDSPRD) [MIM:612716]: A form of DOPA-responsive dystonia.
CC In the majority of cases, patients manifest progressive psychomotor
CC retardation, dystonia and spasticity. Cognitive anomalies are also
CC often present. The disease is due to severe dopamine and serotonin
CC deficiencies in the central nervous system caused by a defect in BH4
CC synthesis. Dystonia is defined by the presence of sustained involuntary
CC muscle contractions, often leading to abnormal postures.
CC {ECO:0000269|PubMed:11443547, ECO:0000269|PubMed:16650784,
CC ECO:0000269|PubMed:17159114}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sepiapterin reductase family. {ECO:0000305}.
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DR EMBL; M76231; AAA60314.1; -; mRNA.
DR EMBL; AK291856; BAF84545.1; -; mRNA.
DR EMBL; AK222942; BAD96662.1; -; mRNA.
DR EMBL; AC092630; AAY15035.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99757.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99758.1; -; Genomic_DNA.
DR EMBL; BC017310; AAH17310.1; -; mRNA.
DR EMBL; AB017547; BAA34534.1; -; Genomic_DNA.
DR CCDS; CCDS1920.1; -.
DR PIR; JQ1176; JQ1176.
DR RefSeq; NP_003115.1; NM_003124.4.
DR PDB; 1Z6Z; X-ray; 2.50 A; A/B/C/D/E/F=5-261.
DR PDB; 4HWK; X-ray; 2.40 A; A/B/C/D=1-261.
DR PDB; 4J7U; X-ray; 2.44 A; A/B/C/D=1-261.
DR PDB; 4J7X; X-ray; 2.60 A; A/B/F/J=1-261.
DR PDB; 4XWY; X-ray; 2.35 A; A/B/C/D=1-261.
DR PDB; 4Z3K; X-ray; 2.35 A; A/B/C/D=1-261.
DR PDB; 6I6C; X-ray; 1.72 A; A/B=1-261.
DR PDB; 6I6F; X-ray; 1.94 A; A/B=1-261.
DR PDB; 6I6P; X-ray; 1.62 A; A/B=1-261.
DR PDB; 6I6T; X-ray; 1.79 A; A/B=1-261.
DR PDB; 6I6V; X-ray; 1.43 A; A/B=1-261.
DR PDB; 6I79; X-ray; 1.63 A; A/B=1-261.
DR PDB; 6USN; X-ray; 2.77 A; A/B/C/D=1-261.
DR PDB; 7DSF; X-ray; 1.80 A; A/B=1-261.
DR PDBsum; 1Z6Z; -.
DR PDBsum; 4HWK; -.
DR PDBsum; 4J7U; -.
DR PDBsum; 4J7X; -.
DR PDBsum; 4XWY; -.
DR PDBsum; 4Z3K; -.
DR PDBsum; 6I6C; -.
DR PDBsum; 6I6F; -.
DR PDBsum; 6I6P; -.
DR PDBsum; 6I6T; -.
DR PDBsum; 6I6V; -.
DR PDBsum; 6I79; -.
DR PDBsum; 6USN; -.
DR PDBsum; 7DSF; -.
DR AlphaFoldDB; P35270; -.
DR SMR; P35270; -.
DR BioGRID; 112575; 87.
DR IntAct; P35270; 5.
DR MINT; P35270; -.
DR STRING; 9606.ENSP00000234454; -.
DR BindingDB; P35270; -.
DR ChEMBL; CHEMBL3988583; -.
DR DrugBank; DB03886; Biopterin.
DR DrugBank; DB04275; N-acetylserotonin.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB02637; Oxaloacetate Ion.
DR GuidetoPHARMACOLOGY; 3020; -.
DR iPTMnet; P35270; -.
DR PhosphoSitePlus; P35270; -.
DR BioMuta; SPR; -.
DR DMDM; 464801; -.
DR EPD; P35270; -.
DR jPOST; P35270; -.
DR MassIVE; P35270; -.
DR MaxQB; P35270; -.
DR PaxDb; P35270; -.
DR PeptideAtlas; P35270; -.
DR PRIDE; P35270; -.
DR ProteomicsDB; 55020; -.
DR Antibodypedia; 31290; 381 antibodies from 30 providers.
DR DNASU; 6697; -.
DR Ensembl; ENST00000234454.6; ENSP00000234454.5; ENSG00000116096.6.
DR GeneID; 6697; -.
DR KEGG; hsa:6697; -.
DR MANE-Select; ENST00000234454.6; ENSP00000234454.5; NM_003124.5; NP_003115.1.
DR UCSC; uc002sik.3; human.
DR CTD; 6697; -.
DR DisGeNET; 6697; -.
DR GeneCards; SPR; -.
DR GeneReviews; SPR; -.
DR HGNC; HGNC:11257; SPR.
DR HPA; ENSG00000116096; Low tissue specificity.
DR MalaCards; SPR; -.
DR MIM; 182125; gene.
DR MIM; 612716; phenotype.
DR neXtProt; NX_P35270; -.
DR OpenTargets; ENSG00000116096; -.
DR Orphanet; 70594; Dopa-responsive dystonia due to sepiapterin reductase deficiency.
DR PharmGKB; PA36087; -.
DR VEuPathDB; HostDB:ENSG00000116096; -.
DR eggNOG; KOG1204; Eukaryota.
DR GeneTree; ENSGT00440000033609; -.
DR HOGENOM; CLU_010194_2_11_1; -.
DR InParanoid; P35270; -.
DR OMA; PYKGWSA; -.
DR OrthoDB; 1089743at2759; -.
DR PhylomeDB; P35270; -.
DR TreeFam; TF326358; -.
DR BioCyc; MetaCyc:HS03979-MON; -.
DR BRENDA; 1.1.1.153; 2681.
DR PathwayCommons; P35270; -.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-HSA-203615; eNOS activation.
DR SABIO-RK; P35270; -.
DR SignaLink; P35270; -.
DR SIGNOR; P35270; -.
DR BioGRID-ORCS; 6697; 15 hits in 1080 CRISPR screens.
DR ChiTaRS; SPR; human.
DR EvolutionaryTrace; P35270; -.
DR GeneWiki; Sepiapterin_reductase; -.
DR GenomeRNAi; 6697; -.
DR Pharos; P35270; Tchem.
DR PRO; PR:P35270; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P35270; protein.
DR Bgee; ENSG00000116096; Expressed in mucosa of transverse colon and 173 other tissues.
DR Genevisible; P35270; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; TAS:UniProtKB.
DR GO; GO:0050661; F:NADP binding; TAS:UniProtKB.
DR GO; GO:0004757; F:sepiapterin reductase activity; ISS:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR InterPro; IPR006393; Sepiapterin_red.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01500; sepiapter_red; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Disease variant; Dystonia; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..261
FT /note="Sepiapterin reductase"
FT /id="PRO_0000072149"
FT BINDING 14..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 42..43
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 69..70
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 157..158
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 201..206
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 213
FT /note="Phosphoserine; by CaMK2; in vitro"
FT /evidence="ECO:0000269|PubMed:11825621"
FT VARIANT 119..261
FT /note="Missing (in DRDSPRD)"
FT /evidence="ECO:0000269|PubMed:11443547"
FT /id="VAR_085775"
FT VARIANT 150
FT /note="R -> G (in DRDSPRD; loss of sepiapterin reductase
FT activity; dbSNP:rs104893665)"
FT /evidence="ECO:0000269|PubMed:11443547,
FT ECO:0000269|PubMed:17159114"
FT /id="VAR_058007"
FT VARIANT 163
FT /note="P -> L (in DRDSPRD; dbSNP:rs104893666)"
FT /evidence="ECO:0000269|PubMed:16650784"
FT /id="VAR_058008"
FT MUTAGEN 213
FT /note="S->A: Abolishes phosphorylation by CaMK2. No effect
FT on kinetic parameters."
FT /evidence="ECO:0000269|PubMed:11825621"
FT CONFLICT 10
FT /note="C -> R (in Ref. 4; BAD96662)"
FT /evidence="ECO:0000305"
FT TURN 2..5
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 7..14
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 18..30
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 44..56
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:4J7X"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 117..127
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 129..141
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 168..187
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 204..212
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 216..228
FT /evidence="ECO:0007829|PDB:6I6V"
FT HELIX 234..247
FT /evidence="ECO:0007829|PDB:6I6V"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:6I6V"
SQ SEQUENCE 261 AA; 28048 MW; 9C9BF76212826F47 CRC64;
MEGGLGRAVC LLTGASRGFG RTLAPLLASL LSPGSVLVLS ARNDEALRQL EAELGAERSG
LRVVRVPADL GAEAGLQQLL GALRELPRPK GLQRLLLINN AGSLGDVSKG FVDLSDSTQV
NNYWALNLTS MLCLTSSVLK AFPDSPGLNR TVVNISSLCA LQPFKGWALY CAGKAARDML
FQVLALEEPN VRVLNYAPGP LDTDMQQLAR ETSVDPDMRK GLQELKAKGK LVDCKVSAQK
LLSLLEKDEF KSGAHVDFYD K
