SPRE_DICDI
ID SPRE_DICDI Reviewed; 267 AA.
AC Q54GP3; Q9NGC5;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Sepiapterin reductase {ECO:0000303|PubMed:10987137, ECO:0000303|PubMed:15896778};
DE Short=SPR;
DE Short=SR {ECO:0000303|PubMed:10987137, ECO:0000303|PubMed:15896778};
DE EC=1.1.1.153 {ECO:0000269|PubMed:10987137, ECO:0000269|PubMed:15896778, ECO:0000269|PubMed:16527408};
GN Name=sprA; ORFNames=DDB_G0290009;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-267, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=AX2;
RX PubMed=10987137;
RA Kim Y.-A., Chung H.J., Kim Y.J., Choi Y.K., Hwang Y.K., Lee S.W.,
RA Park Y.S.;
RT "Characterization of recombinant Dictyostelium discoideum sepiapterin
RT reductase expressed in E. coli.";
RL Mol. Cells 10:405-410(2000).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RC STRAIN=AX2;
RX PubMed=15896778; DOI=10.1016/j.febslet.2005.04.064;
RA Choi Y.K., Park J.S., Kong J.S., Morio T., Park Y.S.;
RT "D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-
RT tetrahydropterin in Dictyostelium discoideum Ax2.";
RL FEBS Lett. 579:3085-3089(2005).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=AX2;
RX PubMed=16527408; DOI=10.1016/j.bbagen.2005.11.017;
RA Choi Y.K., Kong J.S., Park Y.S.;
RT "Functional role of sepiapterin reductase in the biosynthesis of
RT tetrahydropteridines in Dictyostelium discoideum Ax2.";
RL Biochim. Biophys. Acta 1760:877-882(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX2;
RX PubMed=17976377; DOI=10.1016/j.febslet.2007.10.044;
RA Kim H.L., Choi Y.K., Kim do H., Park S.O., Han J., Park Y.S.;
RT "Tetrahydropteridine deficiency impairs mitochondrial function in
RT Dictyostelium discoideum Ax2.";
RL FEBS Lett. 581:5430-5434(2007).
CC -!- FUNCTION: Catalyzes the production of D-threo-tetrahydrobiopterin
CC (tetrahydrodictyopterin or DH4), also known as dictyopterin, and in a
CC much smaller amount that of it's stereoisomer L-erythro-
CC tetrahydrobiopterin ((6R)-L-erythro-5,6,7,8-tetrahydrobiopterin or BH4)
CC (PubMed:16527408). Prefers 1-oxo-2-D-hydroxypropyl-tetrahydropterin to
CC 6-pyruvoyltetrahydropterin (6-pyruvoyl-5,6,7,8-tetrahydropterin) as a
CC substrate, thereby maintaining dominant production of DH4 over BH4 in
CC sufficient supply of an aldose reductase-like enzyme (PubMed:16527408).
CC DH4 represents more than 95% of the total tetrahydrobiopterin
CC production. It has a direct antioxidant function to protect
CC mitochondria against oxidative stress (PubMed:17976377). Essential for
CC the last step of BH4 synthesis (PubMed:10987137, PubMed:15896778). Also
CC catalyzes the conversion of sepiapterin to L-erythro-7,8-
CC dihydrobiopterin, which is then reduced to BH4 by dihydrofolate
CC reductase, constituting the salvage pathway of BH4 (PubMed:10987137).
CC {ECO:0000269|PubMed:10987137, ECO:0000269|PubMed:15896778,
CC ECO:0000269|PubMed:16527408, ECO:0000269|PubMed:17976377}.
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:10987137};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18955;
CC Evidence={ECO:0000269|PubMed:10987137};
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:0000269|PubMed:10987137,
CC ECO:0000269|PubMed:15896778, ECO:0000269|PubMed:16527408};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32629;
CC Evidence={ECO:0000269|PubMed:10987137, ECO:0000269|PubMed:15896778,
CC ECO:0000269|PubMed:16527408};
CC -!- ACTIVITY REGULATION: Inhibited by N-acetylserotonin and to a lesser
CC extent by melatonin. {ECO:0000269|PubMed:10987137}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=51.8 uM for NADPH {ECO:0000269|PubMed:10987137};
CC KM=40 uM for sepiapterin {ECO:0000269|PubMed:10987137};
CC Vmax=0.14 umol/min/mg enzyme {ECO:0000269|PubMed:10987137};
CC pH dependence:
CC Optimum pH is 5.5. {ECO:0000269|PubMed:10987137};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius.
CC {ECO:0000269|PubMed:10987137};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant cells produce about 3% of
CC tetrahydropteridines when compared to wild-type production. They
CC display retarded growth, poor spore viability, impaired mitochondrial
CC function, and increased susceptibility to oxidative stress induced by
CC hydroxylamine or cumene-hydroperoxide. In another mutant, it was found
CC 18% of BH4 and 0.6% of DH4 production of the wild-type level.
CC {ECO:0000269|PubMed:15896778, ECO:0000269|PubMed:17976377}.
CC -!- SIMILARITY: Belongs to the sepiapterin reductase family. {ECO:0000305}.
CC -!- CAUTION: Dictyopterin was not identified in one of the enzymatic assays
CC [PubMed:10987137]. {ECO:0000305}.
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DR EMBL; AAFI02000151; EAL62410.1; -; Genomic_DNA.
DR EMBL; AF253975; AAF67740.1; -; mRNA.
DR RefSeq; XP_635919.1; XM_630827.1.
DR AlphaFoldDB; Q54GP3; -.
DR SMR; Q54GP3; -.
DR STRING; 44689.DDB0191275; -.
DR PaxDb; Q54GP3; -.
DR PRIDE; Q54GP3; -.
DR EnsemblProtists; EAL62410; EAL62410; DDB_G0290009.
DR GeneID; 8627440; -.
DR KEGG; ddi:DDB_G0290009; -.
DR dictyBase; DDB_G0290009; spr.
DR eggNOG; KOG1204; Eukaryota.
DR HOGENOM; CLU_010194_2_11_1; -.
DR InParanoid; Q54GP3; -.
DR OMA; MTVQVQR; -.
DR PhylomeDB; Q54GP3; -.
DR Reactome; R-DDI-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-DDI-203615; eNOS activation.
DR SABIO-RK; Q54GP3; -.
DR PRO; PR:Q54GP3; -.
DR Proteomes; UP000002195; Chromosome 5.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004757; F:sepiapterin reductase activity; IDA:dictyBase.
DR GO; GO:0042559; P:pteridine-containing compound biosynthetic process; IMP:dictyBase.
DR GO; GO:0140460; P:response to Gram-negative bacterium; HDA:dictyBase.
DR GO; GO:0006979; P:response to oxidative stress; IDA:dictyBase.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IDA:dictyBase.
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 Cytoplasm; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..267
FT /note="Sepiapterin reductase"
FT /id="PRO_0000327640"
FT BINDING 10..16
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 41..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 69..70
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 159..160
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 206..211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 267 AA; 30187 MW; 46AB80622D788267 CRC64;
MSKVLAIVTG ASKGFGKAIA QEIVKCNPNK NQLIDLVLFA RSLDGLKSTK ESIETISTNA
KVIDLQSLDM SNIPDVELKF KSVLENIKWE EYSKICFFNN HGTLYHLGRI EDFSDFKNIQ
KDNDTNTTSF VVTTSLLVKK LKELGSQYSS EVTIVNSSSL CAIKAFPTWS LYCSSRAYRD
MFFQALSLEY KLNDKFKVLN YSLGVLDTDM QSQVREECSE DDKSFYVGLK NDGKLINPNR
SASICSNLVY SHKFETGSHL DYYDLDK
