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 27-MAR-2024, entry version 217. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 106. 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 GlyGen; P35270; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P35270; -. DR PhosphoSitePlus; P35270; -. DR SwissPalm; P35270; -. DR BioMuta; SPR; -. DR DMDM; 464801; -. DR EPD; P35270; -. DR jPOST; P35270; -. DR MassIVE; P35270; -. DR MaxQB; P35270; -. DR PaxDb; 9606-ENSP00000234454; -. DR PeptideAtlas; P35270; -. DR ProteomicsDB; 55020; -. DR Pumba; P35270; -. DR Antibodypedia; 31290; 448 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 AGR; HGNC:11257; -. 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; DMFTRTF; -. DR OrthoDB; 64672at2759; -. DR PhylomeDB; P35270; -. DR TreeFam; TF326358; -. DR BioCyc; MetaCyc:HS03979-MONOMER; -. 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 1161 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 175 other cell types or tissues. 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 CDD; cd05367; SPR-like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR002347; SDR_fam. DR InterPro; IPR006393; Sepiapterin_red. DR NCBIfam; TIGR01500; sepiapter_red; 1. DR PANTHER; PTHR44085; SEPIAPTERIN REDUCTASE; 1. DR PANTHER; PTHR44085:SF2; SEPIAPTERIN REDUCTASE; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR Genevisible; P35270; HS. 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 //