Reviewed, UniProtKB/Swiss-Prot P18297 (SPRE_RAT)

Names and origin

Protein names

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

Gene names

Name:

Spr

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	262 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
Catalytic activity	7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH. Tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Post-translational modification	In vitro phosphorylation of Ser-46, Ser-196 and Ser-214 by CaMK2 does not change kinetic parameters.
Sequence similarities	Belongs to the sepiapterin reductase family.
biophysicochemical properties	Kinetic parameters: KM=12.6 µM for sepiapterin Ref.3 KM=2.8 µM for NADPH

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to organic substance Inferred from mutant phenotype. Source: RGD tetrahydrobiopterin biosynthetic process Ref.1 Inferred from mutant phenotype. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	binding Inferred from electronic annotation. Source: InterPro sepiapterin reductase activity Ref.1 Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 262	262	Sepiapterin reductase		PRO_0000072151
Regions
	Nucleotide binding	14 – 40	27	NADP By similarity
	Region	29 – 33	5	Pterin binding By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.2
	Modified residue	46	1	Phosphoserine; by CaMK2; in vitro Ref.3
	Modified residue	196	1	Phosphoserine; by CaMK2; in vitro Ref.3
	Modified residue	214	1	Phosphoserine; by CaMK2; in vitro Ref.3
Experimental info
	Mutagenesis	46	1	S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-196 and A-214. Ref.3
	Mutagenesis	196	1	S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-46 and A-214. Ref.3
	Mutagenesis	214	1	S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters; when associated with A-46 and A-196. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P18297-1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: EC992564A0334C61	FASTA	262	28,128
	10 20 30 40 50 60 MEGGRLGCAV CVLTGASRGF GRALAPQLAG LLSPGSVLLL SARSDSMLRQ LKEELCTQQP 70 80 90 100 110 120 GLQVVLAAAD LGTESGVQQL LSAVRELPRP ERLQRLLLIN NAGTLGDVSK GFLNINDLAE 130 140 150 160 170 180 VNNYWALNLT SMLCLTTGTL NAFSNSPGLS KTVVNISSLC ALQPFKGWGL YCAGKAARDM 190 200 210 220 230 240 LYQVLAVEEP SVRVLSYAPG PLDTNMQQLA RETSMDPELR SRLQKLNSEG ELVDCGTSAQ 250 260 KLLSLLQRDT FQSGAHVDFY DI

References

[1]	"Isolation and expression of rat liver sepiapterin reductase cDNA." Citron B.A., Milstien S., Gutierrez J.C., Levine R.A., Yanak B.L., Kaufman S. Proc. Natl. Acad. Sci. U.S.A. 87:6436-6440(1990) [PubMed: 2201030] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"The complete amino acid sequence of the mature form of rat sepiapterin reductase." Oyama R., Katoh S., Sueoka T., Suzuki M., Ichinose H., Nagatsu T., Titani K. Biochem. Biophys. Res. Commun. 173:627-631(1990) [PubMed: 2260974] [Abstract] Cited for: PROTEIN SEQUENCE.
[3]	"Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II." Fujimoto K., Takahashi S.Y., Katoh S. Biochim. Biophys. Acta 1594:191-198(2002) [PubMed: 11825621] [Abstract] Cited for: KINETIC PARAMETERS, PHOSPHORYLATION AT SER-46; SER-196 AND SER-214, MUTAGENESIS OF SER-46; SER-196 AND SER-214.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M36410 mRNA. Translation: AAA42130.1.
IPI	IPI00189989.
PIR	A36024.
RefSeq	NP_062054.1.
UniGene	Rn.6658
3D structure databases
HSSP	HSSP built from PDB template 1OAA based on UniProtKB Q64105.
SMR	P18297. Positions 6-261.
ModBase	Search...
PTM databases
PhosphoSite	P18297.
Proteomic databases
PRIDE	P18297.
Genome annotation databases
Ensembl	ENSRNOG00000015455. Rattus norvegicus. [Contig view]
GeneID	29270.
KEGG	rno:29270.
Organism-specific databases
RGD	3753. Spr.
Phylogenomic databases
HOVERGEN	P18297.
OMA	P18297. RENKELA.
Enzyme and pathway databases
BRENDA	1.1.1.153. 248.
Gene expression databases
GermOnline	ENSRNOG00000015455. Rattus norvegicus.
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.
PANTHER	PTHR19410. ADH_short_C2. 1 hit.
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH.
TIGRFAMs	TIGR01500. sepiapter_red. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	608616.

Entry information

Entry name

SPRE_RAT

Accession

Primary (citable) accession number: P18297

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	June 16, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)