ID DHPR_HUMAN Reviewed; 244 AA. AC P09417; A8K158; B3KW71; Q53F52; Q9H3M5; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 2. DT 24-JAN-2024, entry version 230. DE RecName: Full=Dihydropteridine reductase; DE EC=1.5.1.34 {ECO:0000269|PubMed:3033643, ECO:0000269|PubMed:8262916}; DE AltName: Full=HDHPR; DE AltName: Full=Quinoid dihydropteridine reductase; DE AltName: Full=Short chain dehydrogenase/reductase family 33C member 1; GN Name=QDPR; Synonyms=DHPR, SDR33C1; 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] (ISOFORM 1), AND VARIANT THR-51. RX PubMed=3031582; DOI=10.1093/nar/15.5.1921; RA Dahl H.-H.M., Hutchison W., McAdam W., Wake S., Morgan F.J., Cotton R.G.H.; RT "Human dihydropteridine reductase: characterisation of a cDNA clone and its RT use in analysis of patients with dihydropteridine reductase deficiency."; RL Nucleic Acids Res. 15:1921-1932(1987). RN [2] RP SEQUENCE REVISION TO 51. RA Dahl H.-H.M.; RL Submitted (JUL-1987) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-51, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=3033643; DOI=10.1073/pnas.84.10.3329; RA Lockyer J., Cook R.G., Milstien S., Kaufman S., Woo S.L.C., Ledley F.D.; RT "Structure and expression of human dihydropteridine reductase."; RL Proc. Natl. Acad. Sci. U.S.A. 84:3329-3333(1987). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-51, AND VARIANTS HPABH4C RP ASP-23; CYS-150; TYR-158 AND ILE-THR-GLY-218 INS. RX PubMed=9744478; RX DOI=10.1002/(sici)1098-1004(1998)12:4<267::aid-humu8>3.0.co;2-c; RA Dianzani I., de Sanctis L., Smooker P.M., Gough T.J., Alliaudi C., RA Brusco A., Spada M., Blau N., Dobos M., Zhang H.-P., Yang N., Ponzone A., RA Armarego W.L.F., Cotton R.G.H.; RT "Dihydropteridine reductase deficiency: physical structure of the QDPR RT gene, identification of two new mutations and genotype-phenotype RT correlations."; RL Hum. Mutat. 12:267-273(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Hsiao K.-J., Yen P.-F., Lin C.-H., Liu T.-T., Chiang S.-H., Chen C.-Y., RA Tsai S.-F.; RT "The complete sequence of human dihydropteridine reductase gene containing RT BAC clone 395N09."; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] 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 [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [11] RP PROTEIN SEQUENCE OF 2-11 AND 128-138, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Gottlieb E.; RL Submitted (MAR-2008) to UniProtKB. RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] 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 [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [16] 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 [17] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8262916; DOI=10.2210/pdb1hdr/pdb; RA Su Y., Varughese K.I., Xuong N.H., Bray T.L., Roche D.J., Whiteley J.M.; RT "The crystallographic structure of a human dihydropteridine reductase NADH RT binary complex expressed in Escherichia coli by a cDNA constructed from its RT rat homologue."; RL J. Biol. Chem. 268:26836-26841(1993). RN [18] RP REVIEW ON VARIANTS. RX PubMed=7627180; DOI=10.1002/humu.1380050402; RA Smooker P.M., Cotton R.G.H.; RT "Molecular basis of dihydropteridine reductase deficiency."; RL Hum. Mutat. 5:279-284(1995). RN [19] RP VARIANTS HPABH4C ASP-23 AND GLY-108. RX PubMed=8326489; DOI=10.1136/jmg.30.6.465; RA Dianzani I., Howells D.W., Ponzone A., Saleeba J.A., Smooker P.M., RA Cotton R.G.H.; RT "Two new mutations in the dihydropteridine reductase gene in patients with RT tetrahydrobiopterin deficiency."; RL J. Med. Genet. 30:465-469(1993). RN [20] RP VARIANT HPABH4C THR-123 INS. RX PubMed=2116088; RA Howells D.W., Forrest S.M., Dahl H.-H.M., Cotton R.G.H.; RT "Insertion of an extra codon for threonine is a cause of dihydropteridine RT reductase deficiency."; RL Am. J. Hum. Genet. 47:279-285(1990). RN [21] RP VARIANTS HPABH4C PRO-14 AND VAL-17. RX PubMed=10408783; RX DOI=10.1002/(sici)1098-1004(1999)13:6<503::aid-humu13>3.0.co;2-f; RA Smooker P.M., Gough T.J., Cotton R.G.H., Alliaudi C., de Sanctis L., RA Dianzani I.; RT "A series of mutations in the dihydropteridine reductase gene resulting in RT either abnormal RNA splicing or DHPR protein defects."; RL Hum. Mutat. 13:503-504(1999). RN [22] RP VARIANTS HPABH4C ARG-17; ASP-18; ASP-23; ARG-66; ARG-149 AND CYS-150. RX PubMed=11153907; DOI=10.1007/s004390000407; RA Romstad A., Kalkanoglu H.S., Coskun T., Demirkol M., Tokatli A., Dursun A., RA Baykal T., Oezalp I., Guldberg P., Guettler F.; RT "Molecular analysis of 16 Turkish families with DHPR deficiency using RT denaturing gradient gel electrophoresis (DGGE)."; RL Hum. Genet. 107:546-553(2000). CC -!- FUNCTION: Catalyzes the conversion of quinonoid dihydrobiopterin into CC tetrahydrobiopterin. {ECO:0000269|PubMed:3033643, CC ECO:0000269|PubMed:8262916}. CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6,7,8-tetrahydropteridine + NAD(+) = 6,7-dihydropteridine + CC H(+) + NADH; Xref=Rhea:RHEA:17869, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28889, ChEBI:CHEBI:30156, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.5.1.34; Evidence={ECO:0000269|PubMed:3033643, CC ECO:0000269|PubMed:8262916}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17871; CC Evidence={ECO:0000305|PubMed:8262916}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6,7,8-tetrahydropteridine + NADP(+) = 6,7-dihydropteridine + CC H(+) + NADPH; Xref=Rhea:RHEA:17865, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28889, ChEBI:CHEBI:30156, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.5.1.34; Evidence={ECO:0000269|PubMed:3033643, CC ECO:0000269|PubMed:8262916}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17867; CC Evidence={ECO:0000305|PubMed:8262916}; CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11348}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P09417-1; Sequence=Displayed; CC Name=2; CC IsoId=P09417-2; Sequence=VSP_054356; CC -!- DISEASE: Hyperphenylalaninemia, BH4-deficient, C (HPABH4C) CC [MIM:261630]: Rare autosomal recessive disorder characterized by CC hyperphenylalaninemia and severe neurologic symptoms (malignant CC hyperphenylalaninemia) including axial hypotonia and truncal CC hypertonia, abnormal thermogenesis, and microcephaly. These signs are CC attributable to depletion of the neurotransmitters dopamine and CC serotonin, whose syntheses are controlled by tryptophan and tyrosine CC hydroxylases that use BH-4 as cofactor. Patients do not respond to CC phenylalanine-restricted diet. HPABH4C is lethal if untreated. CC {ECO:0000269|PubMed:10408783, ECO:0000269|PubMed:11153907, CC ECO:0000269|PubMed:2116088, ECO:0000269|PubMed:8326489, CC ECO:0000269|PubMed:9744478}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC 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; X04882; CAA28571.1; -; mRNA. DR EMBL; M16447; AAA52305.1; -; mRNA. DR EMBL; AJ006239; CAA06930.1; -; Genomic_DNA. DR EMBL; AJ006240; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AJ006241; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AJ006242; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AJ006243; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AJ006244; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AJ006245; CAA06930.1; JOINED; Genomic_DNA. DR EMBL; AB053170; BAB20429.1; -; Genomic_DNA. DR EMBL; AK124382; BAG54033.1; -; mRNA. DR EMBL; AK289773; BAF82462.1; -; mRNA. DR EMBL; AK223437; BAD97157.1; -; mRNA. DR EMBL; AC093600; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471069; EAW92777.1; -; Genomic_DNA. DR EMBL; CH471069; EAW92778.1; -; Genomic_DNA. DR EMBL; BC000576; AAH00576.1; -; mRNA. DR CCDS; CCDS3421.1; -. [P09417-1] DR CCDS; CCDS77904.1; -. [P09417-2] DR PIR; A93655; RDHUP. DR RefSeq; NP_000311.2; NM_000320.2. [P09417-1] DR RefSeq; NP_001293069.1; NM_001306140.1. [P09417-2] DR PDB; 1HDR; X-ray; 2.50 A; A=1-244. DR PDBsum; 1HDR; -. DR AlphaFoldDB; P09417; -. DR SMR; P09417; -. DR BioGRID; 111798; 40. DR IntAct; P09417; 12. DR MINT; P09417; -. DR STRING; 9606.ENSP00000281243; -. DR BindingDB; P09417; -. DR ChEMBL; CHEMBL3730; -. DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid. DR DrugBank; DB00157; NADH. DR iPTMnet; P09417; -. DR MetOSite; P09417; -. DR PhosphoSitePlus; P09417; -. DR SwissPalm; P09417; -. DR BioMuta; QDPR; -. DR DMDM; 118572639; -. DR REPRODUCTION-2DPAGE; IPI00014439; -. DR EPD; P09417; -. DR jPOST; P09417; -. DR MassIVE; P09417; -. DR MaxQB; P09417; -. DR PaxDb; 9606-ENSP00000281243; -. DR PeptideAtlas; P09417; -. DR ProteomicsDB; 3780; -. DR ProteomicsDB; 52216; -. [P09417-1] DR Pumba; P09417; -. DR Antibodypedia; 23074; 241 antibodies from 29 providers. DR DNASU; 5860; -. DR Ensembl; ENST00000281243.10; ENSP00000281243.5; ENSG00000151552.13. [P09417-1] DR Ensembl; ENST00000428702.6; ENSP00000390944.2; ENSG00000151552.13. [P09417-2] DR GeneID; 5860; -. DR KEGG; hsa:5860; -. DR MANE-Select; ENST00000281243.10; ENSP00000281243.5; NM_000320.3; NP_000311.2. DR UCSC; uc003gpd.4; human. [P09417-1] DR AGR; HGNC:9752; -. DR CTD; 5860; -. DR DisGeNET; 5860; -. DR GeneCards; QDPR; -. DR HGNC; HGNC:9752; QDPR. DR HPA; ENSG00000151552; Group enriched (brain, liver). DR MalaCards; QDPR; -. DR MIM; 261630; phenotype. DR MIM; 612676; gene. DR neXtProt; NX_P09417; -. DR OpenTargets; ENSG00000151552; -. DR Orphanet; 226; Dihydropteridine reductase deficiency. DR PharmGKB; PA34094; -. DR VEuPathDB; HostDB:ENSG00000151552; -. DR eggNOG; KOG4022; Eukaryota. DR GeneTree; ENSGT00390000000470; -. DR HOGENOM; CLU_010194_22_0_1; -. DR InParanoid; P09417; -. DR OMA; TEMNRKW; -. DR OrthoDB; 276282at2759; -. DR PhylomeDB; P09417; -. DR TreeFam; TF105932; -. DR BioCyc; MetaCyc:HS07746-MONOMER; -. DR BRENDA; 1.5.1.34; 2681. DR PathwayCommons; P09417; -. DR Reactome; R-HSA-8964208; Phenylalanine metabolism. DR SABIO-RK; P09417; -. DR SignaLink; P09417; -. DR BioGRID-ORCS; 5860; 13 hits in 1165 CRISPR screens. DR ChiTaRS; QDPR; human. DR EvolutionaryTrace; P09417; -. DR GeneWiki; QDPR; -. DR GenomeRNAi; 5860; -. DR Pharos; P09417; Tchem. DR PRO; PR:P09417; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P09417; Protein. DR Bgee; ENSG00000151552; Expressed in inferior vagus X ganglion and 198 other cell types or tissues. DR ExpressionAtlas; P09417; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0004155; F:6,7-dihydropteridine reductase activity; IDA:UniProtKB. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0070404; F:NADH binding; IBA:GO_Central. DR GO; GO:0070402; F:NADPH binding; IBA:GO_Central. DR GO; GO:0006520; P:amino acid metabolic process; TAS:ProtInc. DR GO; GO:0051066; P:dihydrobiopterin metabolic process; TAS:ProtInc. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central. DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IBA:GO_Central. DR CDD; cd05334; DHPR_SDR_c_like; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020904; Sc_DH/Rdtase_CS. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR15104; DIHYDROPTERIDINE REDUCTASE; 1. DR PANTHER; PTHR15104:SF0; DIHYDROPTERIDINE REDUCTASE; 1. DR Pfam; PF00106; adh_short; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00061; ADH_SHORT; 1. DR UCD-2DPAGE; P09417; -. DR Genevisible; P09417; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Disease variant; NADP; Oxidoreductase; Phenylketonuria; Reference proteome; KW Tetrahydrobiopterin biosynthesis. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..244 FT /note="Dihydropteridine reductase" FT /id="PRO_0000054636" FT ACT_SITE 150 FT /note="Proton acceptor" FT BINDING 14..38 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 73 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BVI4" FT MOD_RES 79 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BVI4" FT MOD_RES 96 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BVI4" FT MOD_RES 102 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BVI4" FT VAR_SEQ 36..66 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054356" FT VARIANT 14 FT /note="L -> P (in HPABH4C; severe; dbSNP:rs756639609)" FT /evidence="ECO:0000269|PubMed:10408783" FT /id="VAR_008121" FT VARIANT 17 FT /note="G -> R (in HPABH4C; severe; dbSNP:rs757483045)" FT /evidence="ECO:0000269|PubMed:11153907" FT /id="VAR_021767" FT VARIANT 17 FT /note="G -> V (in HPABH4C; severe)" FT /evidence="ECO:0000269|PubMed:10408783" FT /id="VAR_008122" FT VARIANT 18 FT /note="G -> D (in HPABH4C; severe; dbSNP:rs1278371188)" FT /evidence="ECO:0000269|PubMed:11153907" FT /id="VAR_021768" FT VARIANT 23 FT /note="G -> D (in HPABH4C; severe; dbSNP:rs104893863)" FT /evidence="ECO:0000269|PubMed:11153907, FT ECO:0000269|PubMed:8326489, ECO:0000269|PubMed:9744478" FT /id="VAR_006960" FT VARIANT 36 FT /note="W -> R (in HPABH4C; dbSNP:rs104893865)" FT /id="VAR_006961" FT VARIANT 51 FT /note="S -> T" FT /evidence="ECO:0000269|PubMed:3031582, FT ECO:0000269|PubMed:3033643, ECO:0000269|PubMed:9744478" FT /id="VAR_013027" FT VARIANT 66 FT /note="Q -> R (in HPABH4C; severe; dbSNP:rs1252488251)" FT /evidence="ECO:0000269|PubMed:11153907" FT /id="VAR_021769" FT VARIANT 74 FT /note="L -> P (in HPABH4C; dbSNP:rs1158304986)" FT /id="VAR_006962" FT VARIANT 108 FT /note="W -> G (in HPABH4C; dbSNP:rs104893864)" FT /evidence="ECO:0000269|PubMed:8326489" FT /id="VAR_006963" FT VARIANT 123 FT /note="T -> TT (in HPABH4C)" FT /evidence="ECO:0000269|PubMed:2116088" FT /id="VAR_006964" FT VARIANT 145 FT /note="P -> L (in HPABH4C; dbSNP:rs1560312943)" FT /id="VAR_006965" FT VARIANT 149 FT /note="G -> R (in HPABH4C; dbSNP:rs1028029163)" FT /evidence="ECO:0000269|PubMed:11153907" FT /id="VAR_021770" FT VARIANT 150 FT /note="Y -> C (in HPABH4C; mild; dbSNP:rs104893866)" FT /evidence="ECO:0000269|PubMed:11153907, FT ECO:0000269|PubMed:9744478" FT /id="VAR_006966" FT VARIANT 151 FT /note="G -> S (in HPABH4C; mild)" FT /id="VAR_006967" FT VARIANT 158 FT /note="H -> Y (in HPABH4C; severe; dbSNP:rs750201480)" FT /evidence="ECO:0000269|PubMed:9744478" FT /id="VAR_006968" FT VARIANT 170 FT /note="G -> S (in HPABH4C; dbSNP:rs769460415)" FT /id="VAR_006969" FT VARIANT 212 FT /note="F -> C (in HPABH4C; mild; dbSNP:rs777797545)" FT /id="VAR_006970" FT VARIANT 218 FT /note="G -> GITG (in HPABH4C; mild)" FT /id="VAR_006971" FT STRAND 11..16 FT /evidence="ECO:0007829|PDB:1HDR" FT TURN 17..19 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 21..32 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 36..43 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 48..53 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 60..75 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 80..85 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 100..110 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 112..125 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 126..135 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 138..141 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 148..165 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 176..181 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 188..191 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 199..201 FT /evidence="ECO:0007829|PDB:1HDR" FT HELIX 205..216 FT /evidence="ECO:0007829|PDB:1HDR" FT TURN 217..220 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 227..233 FT /evidence="ECO:0007829|PDB:1HDR" FT STRAND 236..242 FT /evidence="ECO:0007829|PDB:1HDR" SQ SEQUENCE 244 AA; 25790 MW; 0852F9F0CA38AB1C CRC64; MAAAAAAGEA RRVLVYGGRG ALGSRCVQAF RARNWWVASV DVVENEEASA SIIVKMTDSF TEQADQVTAE VGKLLGEEKV DAILCVAGGW AGGNAKSKSL FKNCDLMWKQ SIWTSTISSH LATKHLKEGG LLTLAGAKAA LDGTPGMIGY GMAKGAVHQL CQSLAGKNSG MPPGAAAIAV LPVTLDTPMN RKSMPEADFS SWTPLEFLVE TFHDWITGKN RPSSGSLIQV VTTEGRTELT PAYF //