DHPR_HUMAN
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 03-AUG-2022, entry version 222.
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}.
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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; 36.
DR IntAct; P09417; 11.
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 UCD-2DPAGE; P09417; -.
DR EPD; P09417; -.
DR jPOST; P09417; -.
DR MassIVE; P09417; -.
DR MaxQB; P09417; -.
DR PaxDb; P09417; -.
DR PeptideAtlas; P09417; -.
DR PRIDE; P09417; -.
DR ProteomicsDB; 3780; -.
DR ProteomicsDB; 52216; -. [P09417-1]
DR Antibodypedia; 23074; 223 antibodies from 29 providers.
DR DNASU; 5860; -.
DR Ensembl; ENST00000281243.10; ENSP00000281243.5; ENSG00000151552.12. [P09417-1]
DR Ensembl; ENST00000428702.6; ENSP00000390944.2; ENSG00000151552.12. [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 CTD; 5860; -.
DR DisGeNET; 5860; -.
DR GeneCards; QDPR; -.
DR HGNC; HGNC:9752; QDPR.
DR HPA; ENSG00000151552; Tissue enhanced (brain, choroid plexus).
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; DWWVASI; -.
DR PhylomeDB; P09417; -.
DR TreeFam; TF105932; -.
DR BioCyc; MetaCyc:HS07746-MON; -.
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; 12 hits in 1084 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 196 other tissues.
DR ExpressionAtlas; P09417; baseline and differential.
DR Genevisible; P09417; HS.
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:cellular 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 InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
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
