Q54GP3 (SPRE_DICDI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sepiapterin reductase
Short name=SPR
EC=1.1.1.153

Gene names

Name:	sprA
ORF Names:	DDB_G0290009

Organism

Dictyostelium discoideum (Slime mold)

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the production of D-threo-tetrahydrobiopterin (DH4), also known as dictyopterin, and in a much smaller amount that of it's stereoisomer L-erythro-tetrahydrobiopterin (BH4). Prefers 1-oxo-2-D-hydroxypropyl-tetrahydropterin to 6-pyruvoyltetrahydropterin as a substrate, thereby maintaining dominant production of DH4 over BH4 in sufficient supply of an aldose reductase-like enzyme. DH4 represents more than 95% of the total tetrahydrobiopterin production. It has a direct antioxidant function to protect mitochondria against oxidative stress. Ref.3 Ref.4 Ref.5
Catalytic activity	7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH. Ref.2 Ref.3 Ref.4 Tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH. Ref.2 Ref.3 Ref.4
Enzyme regulation	Inhibited by N-acetylserotonin and to a lesser extent by melatonin.
Subcellular location	Cytoplasm By similarity.
Disruption phenotype	Mutant cells produce about 3% of tetrahydropteridines when compared to wild-type production. They display retarded growth, poor spore viability, impaired mitochondrial function, and increased susceptibility to oxidative stress induced by hydroxylamine or cumene-hydroperoxide. In another mutant, it was found 18% of BH4 and 0.6% of DH4 production of the wild-type level. Ref.3 Ref.5
Sequence similarities	Belongs to the sepiapterin reductase family.
Caution	Dictyopterin was not identified in one of the enzymatic assays [Ref.2].
Biophysicochemical properties	Kinetic parameters: KM=51.8 µM for NADPH Ref.2 KM=40 µM for sepiapterin Vmax=0.14 µmol/min/mg enzyme pH dependence: Optimum pH is 5.5. Temperature dependence: Optimum temperature is 30 degrees Celsius.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	tetrahydrobiopterin biosynthetic process Inferred from direct assay Ref.2. Source: dictyBase
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Inferred from direct assay Ref.4. Source: dictyBase
Molecular function	nucleotide binding Inferred from electronic annotation. Source: InterPro sepiapterin reductase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 267	267	Sepiapterin reductase		PRO_0000327640
Regions
	Nucleotide binding	10 – 16	7	NADP By similarity
	Nucleotide binding	41 – 42	2	NADP By similarity
	Nucleotide binding	69 – 70	2	NADP By similarity
	Nucleotide binding	206 – 211	6	NADP By similarity
	Region	159 – 160	2	Substrate binding By similarity
Sites
	Binding site	172	1	Substrate By similarity
	Binding site	176	1	NADP By similarity
	Binding site	204	1	Substrate; via amide nitrogen By similarity
	Binding site	261	1	Substrate By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q54GP3 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: 46AB80622D788267	FASTA	267	30,187
	10 20 30 40 50 60 MSKVLAIVTG ASKGFGKAIA QEIVKCNPNK NQLIDLVLFA RSLDGLKSTK ESIETISTNA 70 80 90 100 110 120 KVIDLQSLDM SNIPDVELKF KSVLENIKWE EYSKICFFNN HGTLYHLGRI EDFSDFKNIQ 130 140 150 160 170 180 KDNDTNTTSF VVTTSLLVKK LKELGSQYSS EVTIVNSSSL CAIKAFPTWS LYCSSRAYRD 190 200 210 220 230 240 MFFQALSLEY KLNDKFKVLN YSLGVLDTDM QSQVREECSE DDKSFYVGLK NDGKLINPNR 250 260 SASICSNLVY SHKFETGSHL DYYDLDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[2]	"Characterization of recombinant Dictyostelium discoideum sepiapterin reductase expressed in E. coli." Kim Y.-A., Chung H.J., Kim Y.J., Choi Y.K., Hwang Y.K., Lee S.W., Park Y.S. Mol. Cells 10:405-410(2000) [PubMed: 10987137] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-267, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES. Strain: AX2.
[3]	"D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum Ax2." Choi Y.K., Park J.S., Kong J.S., Morio T., Park Y.S. FEBS Lett. 579:3085-3089(2005) [PubMed: 15896778] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY. Strain: AX2.
[4]	"Functional role of sepiapterin reductase in the biosynthesis of tetrahydropteridines in Dictyostelium discoideum Ax2." Choi Y.K., Kong J.S., Park Y.S. Biochim. Biophys. Acta 1760:877-882(2006) [PubMed: 16527408] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY. Strain: AX2.
[5]	"Tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2." Kim H.L., Choi Y.K., Kim do H., Park S.O., Han J., Park Y.S. FEBS Lett. 581:5430-5434(2007) [PubMed: 17976377] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE. Strain: AX2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AAFI02000151 Genomic DNA. Translation: EAL62410.1. AF253975 mRNA. Translation: AAF67740.1.
RefSeq	XP_635919.1. XM_630827.1.
3D structure databases
HSSP	HSSP built from PDB template 1Z6Z based on UniProtKB P35270.
ProteinModelPortal	Q54GP3.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblProtists	DDB0191275; DDB0191275; DDB_G0290009.
GeneID	8627440.
GenomeReviews	Gene locus sprA in contig CM000154_GR.
KEGG	ddi:DDB_G0290009.
Organism-specific databases
dictyBase	DDB_G0290009. sr.
Phylogenomic databases
eggNOG	KOG1204.
GeneTree	EPrGT00050000003275.
OMA	NIRNEEV.
PhylomeDB	Q54GP3.
ProtClustDB	CLSZ2497108.
Family and domain databases
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. IPR006393. Sepiapterin_red. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
KO	K00072.
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH.
TIGRFAMs	TIGR01500. Sepiapter_red. 1 hit.
ProtoNet	Search...

Entry information

Entry name

SPRE_DICDI

Accession

Primary (citable) accession number: Q54GP3
Secondary accession number(s): Q9NGC5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	May 24, 2005
Last modified:	December 14, 2011
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)