Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	261	2p13.2	SPR	sepiapterin reductase
Mouse	-	262	6 C3; 6 37.15 cM	Spr	sepiapterin reductase
Rat	-	262	4q34	Spr	sepiapterin reductase

Previous and Unofficial Names

SDR38C1 | sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) | short chain dehydrogenase/reductase family 38C, member 1

Database Links
Alphafold	P35270 (Hs), P18297 (Rn)
BRENDA	1.1.1.153
ChEMBL Target	CHEMBL3988583 (Hs)
Ensembl Gene	ENSG00000116096 (Hs), ENSMUSG00000033735 (Mm), ENSRNOG00000015455 (Rn)
Entrez Gene	6697 (Hs), 20751 (Mm), 29270 (Rn)
Human Protein Atlas	ENSG00000116096 (Hs)
KEGG Enzyme	1.1.1.153
KEGG Gene	hsa:6697 (Hs), mmu:20751 (Mm), rno:29270 (Rn)
OMIM	182125 (Hs)
Pharos	P35270 (Hs)
RefSeq Nucleotide	NM_011467 (Hs), NM_003124 (Hs), NM_019181 (Rn)
RefSeq Protein	NP_003115 (Hs), NP_035597 (Mm), NP_062054 (Rn)
UniProtKB	P35270 (Hs), P18297 (Rn)
Wikipedia	SPR (Hs)

Selected 3D Structures
	Description:  Crystal structure of human sepiapterin reductase in complex with an N-acetylserotinin analogue PDB Id:  4XWY Ligand:  SPRi3 Resolution:  2.35Å Species:  Human References:  3

Enzyme Reaction
EC Number: 1.1.1.153 Description Reaction Reference De novo synthesis of tetrahydrobiopterin from GTP, and synthesis of the erythro form of tetrahydrobiopterin L-erythro-7,8-dihydrobiopterin + NADP(+) <=> sepiapterin + NADPH L-erythro-tetrahydrobiopterin + 2 NADP(+) <=> 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference SPRi3 Hs Inhibition 8.0 pIC50 1 ⤷ pIC50 8.0 (IC50 1.1x10-8 M) [1] Description: In a chromogenic cell-free enzyme assay.

Immunopharmacology Comments

BH4 has been reported as a crucial regulator of T cell function and proliferation [2]. As a result, modulation of enzymes in the BH4 biosynthesis pathway has been suggested as a novel mechanistic approach for the treatment of autoimmune diseases (pathway inhibitors to reduce T cell activity) and anticancer immunity (pathway activators to enhance T cell effector function). In support of this hypothesis, the sepiapterin reductase (SPR; the terminal enzyme in BH4 biosynthesis) inhibitor SPRi3, has been shown to reduce neuropathic and inflammatory pain in vivo [3].

General Comments
SPR is an aldo-keto reductase that catalyses the terminal reaction in the biosynthesis of tetrahydrobiopterin (BH4, sapropterin) from GTP.