SPRE_MOUSE
ID SPRE_MOUSE Reviewed; 261 AA.
AC Q64105; Q63996;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Sepiapterin reductase;
DE Short=SPR;
DE EC=1.1.1.153;
GN Name=Spr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7873607; DOI=10.1016/0167-4781(94)00225-r;
RA Ota A., Ichinose H., Nagatsu T.;
RT "Mouse sepiapterin reductase: an enzyme involved in the final step of
RT tetrahydrobiopterin biosynthesis. Primary structure deduced from the cDNA
RT sequence.";
RL Biochim. Biophys. Acta 1260:320-322(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=10209270; DOI=10.1016/s0167-4781(99)00030-5;
RA Lee S.W., Park I.Y., Hahn Y., Lee J.E., Seong C.S., Chung J.H., Park Y.S.;
RT "Cloning of mouse sepiapterin reductase gene and characterization of its
RT promoter region.";
RL Biochim. Biophys. Acta 1445:165-171(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 209-261.
RX PubMed=8304109; DOI=10.1007/978-1-4615-2960-6_39;
RA Maier J., Schott K., Werner T., Bacher A., Ziegler I.;
RT "Northern blot analysis of sepiapterin reductase mRNA in mammalian cell
RT lines and tissues.";
RL Adv. Exp. Med. Biol. 338:195-198(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 209-255.
RX PubMed=8440319; DOI=10.1006/excr.1993.1027;
RA Maier J., Schott K., Werner T., Bacher A., Ziegler I.;
RT "Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various
RT cells and tissues of various species.";
RL Exp. Cell Res. 204:217-222(1993).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEXES WITH PTERIN; N-ACETYL
RP SEROTONIN AND NADP, ENZYME MECHANISM, AND SUBUNIT.
RX PubMed=9405351; DOI=10.1093/emboj/16.24.7219;
RA Auerbach G., Herrmann A., Gutlich M., Fischer M., Jacob U., Bacher A.,
RA Huber R.;
RT "The 1.25-A crystal structure of sepiapterin reductase reveals its binding
RT mode to pterins and brain neurotransmitters.";
RL EMBO J. 16:7219-7230(1997).
CC -!- FUNCTION: Catalyzes the final one or two reductions in tetra-
CC hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
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 -!- 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;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9405351}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the sepiapterin reductase family. {ECO:0000305}.
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DR EMBL; S77493; AAB33611.1; -; mRNA.
DR EMBL; U78077; AAC69364.1; -; Genomic_DNA.
DR EMBL; U78076; AAC69364.1; JOINED; Genomic_DNA.
DR EMBL; S71375; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; S52110; S52110.
DR PDB; 1NAS; X-ray; 2.10 A; A=3-261.
DR PDB; 1OAA; X-ray; 1.25 A; A=3-261.
DR PDB; 1SEP; X-ray; 1.95 A; A=1-261.
DR PDBsum; 1NAS; -.
DR PDBsum; 1OAA; -.
DR PDBsum; 1SEP; -.
DR AlphaFoldDB; Q64105; -.
DR SMR; Q64105; -.
DR IntAct; Q64105; 2.
DR MINT; Q64105; -.
DR STRING; 10090.ENSMUSP00000048111; -.
DR iPTMnet; Q64105; -.
DR PhosphoSitePlus; Q64105; -.
DR SwissPalm; Q64105; -.
DR REPRODUCTION-2DPAGE; Q64105; -.
DR EPD; Q64105; -.
DR jPOST; Q64105; -.
DR MaxQB; Q64105; -.
DR PaxDb; Q64105; -.
DR PeptideAtlas; Q64105; -.
DR PRIDE; Q64105; -.
DR ProteomicsDB; 261631; -.
DR MGI; MGI:103078; Spr.
DR eggNOG; KOG1204; Eukaryota.
DR InParanoid; Q64105; -.
DR BRENDA; 1.1.1.153; 3474.
DR Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-MMU-203615; eNOS activation.
DR ChiTaRS; Spr; mouse.
DR EvolutionaryTrace; Q64105; -.
DR PRO; PR:Q64105; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q64105; protein.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0004757; F:sepiapterin reductase activity; ISS:UniProtKB.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IMP:MGI.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:MGI.
DR GO; GO:0006558; P:L-phenylalanine metabolic process; IMP:MGI.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0042415; P:norepinephrine metabolic process; IMP:MGI.
DR GO; GO:0019889; P:pteridine metabolic process; IMP:MGI.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0042428; P:serotonin metabolic process; IMP:MGI.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; ISO:MGI.
DR GO; GO:0046146; P:tetrahydrobiopterin metabolic process; IMP:MGI.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI.
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 3D-structure; Acetylation; Cytoplasm; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..261
FT /note="Sepiapterin reductase"
FT /id="PRO_0000072150"
FT BINDING 15..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 43..44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 70..71
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 158..159
FT /ligand="substrate"
FT BINDING 171
FT /ligand="substrate"
FT BINDING 175
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 200
FT /ligand="substrate"
FT BINDING 202..207
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 222
FT /ligand="substrate"
FT BINDING 258
FT /ligand="substrate"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18297"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35270"
FT CONFLICT 4
FT /note="D -> G (in Ref. 2; AAC69364)"
FT /evidence="ECO:0000305"
FT STRAND 7..15
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 45..58
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 74..86
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 118..128
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 169..188
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 192..198
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 205..213
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:1OAA"
FT HELIX 235..248
FT /evidence="ECO:0007829|PDB:1OAA"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:1OAA"
SQ SEQUENCE 261 AA; 27883 MW; 102294E439CB8AEC CRC64;
MEADGLGCAV CVLTGASRGF GRALAPQLAR LLSPGSVMLV SARSESMLRQ LKEELGAQQP
DLKVVLAAAD LGTEAGVQRL LSAVRELPRP EGLQRLLLIN NAATLGDVSK GFLNVNDLAE
VNNYWALNLT SMLCLTSGTL NAFQDSPGLS KTVVNISSLC ALQPYKGWGL YCAGKAARDM
LYQVLAAEEP SVRVLSYAPG PLDNDMQQLA RETSKDPELR SKLQKLKSDG ALVDCGTSAQ
KLLGLLQKDT FQSGAHVDFY D
