DHPR_RAT
ID DHPR_RAT Reviewed; 241 AA.
AC P11348;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Dihydropteridine reductase;
DE EC=1.5.1.34 {ECO:0000269|PubMed:1898002};
DE AltName: Full=HDHPR;
DE AltName: Full=Quinoid dihydropteridine reductase;
GN Name=Qdpr; Synonyms=Dhpr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=3680258; DOI=10.1016/s0021-9258(18)49271-x;
RA Shahbaz M., Hoch J.A., Trach K.A., Hural J.A., Webber S., Whiteley J.M.;
RT "Structural studies and isolation of cDNA clones providing the complete
RT sequence of rat liver dihydropteridine reductase.";
RL J. Biol. Chem. 262:16412-16416(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [3]
RP PROTEIN SEQUENCE OF 10-16; 53-70; 77-93; 100-121; 125-164 AND 218-241, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Hippocampus;
RA Lubec G., Chen W.-Q., Kang S.U.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP PROTEIN SEQUENCE OF 13-14; 105-128; 192-220 AND 236-241.
RC TISSUE=Liver;
RX PubMed=3566737; DOI=10.1016/0006-291x(87)91393-3;
RA Webber S., Hural J., Whiteley J.M.;
RT "Preliminary studies on the primary structure of rat liver dihydropteridine
RT reductase.";
RL Biochem. Biophys. Res. Commun. 143:582-586(1987).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ALA-7; ASP-38 AND TRP-105, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1898002; DOI=10.1016/0003-9861(91)90412-c;
RA Matthews D.A., Varughese K.I., Skinner M.M., Xuing N.H., Hoch J.A.,
RA Trach K.A., Schneider M., Bray T., Whiteley J.M.;
RT "Role of aspartate-37 in determining cofactor specificity and binding in
RT rat liver dihydropteridine reductase.";
RL Arch. Biochem. Biophys. 287:234-239(1991).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), AND SUBUNIT.
RX PubMed=1631094; DOI=10.1073/pnas.89.13.6080;
RA Varughese K.I., Skinner M.M., Whiteley J.M., Matthews D.A., Xuong N.H.;
RT "Crystal structure of rat liver dihydropteridine reductase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6080-6084(1992).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 6-241.
RX PubMed=8304094; DOI=10.1007/978-1-4615-2960-6_24;
RA Varughese K.I., Su Y., Skinner M.M., Xuong N.H., Matthews D.A.,
RA Whiteley J.M.;
RT "Two crystal structures of rat liver dihydropteridine reductase.";
RL Adv. Exp. Med. Biol. 338:123-126(1993).
CC -!- FUNCTION: Catalyzes the conversion of quinonoid dihydrobiopterin into
CC tetrahydrobiopterin. {ECO:0000269|PubMed:1898002}.
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;
CC Evidence={ECO:0000269|PubMed:1898002};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17871;
CC Evidence={ECO:0000269|PubMed:1898002};
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;
CC Evidence={ECO:0000269|PubMed:1898002};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17867;
CC Evidence={ECO:0000269|PubMed:1898002};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13 uM for NADH {ECO:0000269|PubMed:1898002};
CC Note=kcat is 156 s(-1) for NADH. {ECO:0000269|PubMed:1898002};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1631094}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; J03481; AAA41099.1; -; mRNA.
DR EMBL; BC072536; AAH72536.1; -; mRNA.
DR PIR; A28473; RDRTP.
DR RefSeq; NP_071785.1; NM_022390.1.
DR PDB; 1DHR; X-ray; 2.30 A; A=1-241.
DR PDB; 1DIR; X-ray; 2.60 A; A/B/C/D=1-241.
DR PDBsum; 1DHR; -.
DR PDBsum; 1DIR; -.
DR AlphaFoldDB; P11348; -.
DR SMR; P11348; -.
DR STRING; 10116.ENSRNOP00000004385; -.
DR BindingDB; P11348; -.
DR ChEMBL; CHEMBL2910; -.
DR iPTMnet; P11348; -.
DR PhosphoSitePlus; P11348; -.
DR jPOST; P11348; -.
DR PaxDb; P11348; -.
DR PRIDE; P11348; -.
DR GeneID; 64192; -.
DR KEGG; rno:64192; -.
DR CTD; 5860; -.
DR RGD; 619915; Qdpr.
DR VEuPathDB; HostDB:ENSRNOG00000003253; -.
DR eggNOG; KOG4022; Eukaryota.
DR HOGENOM; CLU_010194_22_0_1; -.
DR InParanoid; P11348; -.
DR OMA; DWWVASI; -.
DR OrthoDB; 1585354at2759; -.
DR PhylomeDB; P11348; -.
DR TreeFam; TF105932; -.
DR Reactome; R-RNO-8964208; Phenylalanine metabolism.
DR SABIO-RK; P11348; -.
DR EvolutionaryTrace; P11348; -.
DR PRO; PR:P11348; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000003253; Expressed in Ammon's horn and 19 other tissues.
DR Genevisible; P11348; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0004155; F:6,7-dihydropteridine reductase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0070404; F:NADH binding; IPI:RGD.
DR GO; GO:0070402; F:NADPH binding; IMP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0010044; P:response to aluminum ion; IEP:RGD.
DR GO; GO:0033762; P:response to glucagon; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IDA:RGD.
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; Direct protein sequencing; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Tetrahydrobiopterin biosynthesis.
FT CHAIN 1..241
FT /note="Dihydropteridine reductase"
FT /id="PRO_0000054639"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT BINDING 11..35
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT MOD_RES 70
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BVI4"
FT MOD_RES 76
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BVI4"
FT MOD_RES 93
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BVI4"
FT MOD_RES 99
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BVI4"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 7
FT /note="A->V: No significant effect on catalytic efficiency
FT for NADH."
FT /evidence="ECO:0000269|PubMed:1898002"
FT MUTAGEN 38
FT /note="D->I: 3-fold decrease in catalytic efficiency for
FT NADH."
FT /evidence="ECO:0000269|PubMed:1898002"
FT MUTAGEN 105
FT /note="W->F: No significant effect on catalytic efficiency
FT for NADH."
FT /evidence="ECO:0000269|PubMed:1898002"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:1DHR"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:1DHR"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 57..72
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 97..122
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 123..132
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 145..161
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 185..190
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:1DHR"
FT HELIX 202..213
FT /evidence="ECO:0007829|PDB:1DHR"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:1DHR"
FT STRAND 233..239
FT /evidence="ECO:0007829|PDB:1DHR"
SQ SEQUENCE 241 AA; 25552 MW; D9F7A5163E4B86EF CRC64;
MAASGEARRV LVYGGRGALG SRCVQAFRAR NWWVASIDVV ENEEASASVI VKMTDSFTEQ
ADQVTAEVGK LLGDQKVDAI LCVAGGWAGG NAKSKSLFKN CDLMWKQSIW TSTISSHLAT
KHLKEGGLLT LAGAKAALDG TPGMIGYGMA KGAVHQLCQS LAGKNSGMPS GAAAIAVLPV
TLDTPMNRKS MPEADFSSWT PLEFLVETFH DWITGNKRPN SGSLIQVVTT DGKTELTPAY
F
