Reviewed, UniProtKB/Swiss-Prot P35270 (SPRE_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

SPR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	261 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-213 by CaMK2 does not change kinetic parameters.
Involvement in disease	Depressed synthesis of tetrahydrobiopterin may play a role in a variety of human diseases.
Sequence similarities	Belongs to the sepiapterin reductase family.
biophysicochemical properties	Kinetic parameters: KM=14.3 µM for sepiapterin Ref.9 KM=10 µM for NADPH

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	nitric oxide biosynthetic process Inferred from direct assay. Source: UniProtKB oxidation reduction Ref.1 Traceable author statement. Source: UniProtKB tetrahydrobiopterin biosynthetic process Ref.1 Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NADP or NADPH binding Ref.1 Traceable author statement. Source: UniProtKB aldo-keto reductase activity Ref.1 Traceable author statement. Source: UniProtKB sepiapterin reductase activity Ref.8 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 261

261

Sepiapterin reductase

PRO_0000072149

Regions

Nucleotide binding

13 – 39

27

NADP By similarity

Region

28 – 32

5

Pterin binding By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

213

1

Phosphoserine; by CaMK2; in vitro Ref.9

Experimental info

Mutagenesis

213

1

S → A: Abolishes phosphorylation by CaMK2. No effect on kinetic parameters. Ref.9

Sequence conflict

10

1

C → R in BAD96662. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

261

Helix Strand Turn

Details...

Beta strand

6 – 14

9

Helix

18 – 28

11

Beta strand

36 – 42

7

Helix

44 – 52

9

Helix

56 – 59

4

Beta strand

62 – 67

6

Helix

73 – 84

12

Beta strand

94 – 99

6

Helix

111 – 113

3

Helix

117 – 127

11

Helix

129 – 141

13

Beta strand

149 – 155

7

Helix

158 – 160

3

Helix

168 – 187

20

Beta strand

191 – 197

7

Beta strand

200 – 203

4

Helix

204 – 212

9

Helix

216 – 227

12

Helix

234 – 247

14

Beta strand

255 – 257

3

Sequences

	Sequence		Length	Mass (Da)
	P35270-1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 9C9BF76212826F47	FASTA	261	28,048
	10 20 30 40 50 60 MEGGLGRAVC LLTGASRGFG RTLAPLLASL LSPGSVLVLS ARNDEALRQL EAELGAERSG 70 80 90 100 110 120 LRVVRVPADL GAEAGLQQLL GALRELPRPK GLQRLLLINN AGSLGDVSKG FVDLSDSTQV 130 140 150 160 170 180 NNYWALNLTS MLCLTSSVLK AFPDSPGLNR TVVNISSLCA LQPFKGWALY CAGKAARDML 190 200 210 220 230 240 FQVLALEEPN VRVLNYAPGP LDTDMQQLAR ETSVDPDMRK GLQELKAKGK LVDCKVSAQK 250 260 LLSLLEKDEF KSGAHVDFYD K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of cDNA encoding human sepiapterin reductase -- an enzyme involved in tetrahydrobiopterin biosynthesis." Ichinose H., Katoh S., Sueoka T., Titani K., Fujita K., Nagatsu T. Biochem. Biophys. Res. Commun. 179:183-189(1991) [PubMed: 1883349] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species." Maier J., Schott K., Werner T., Bacher A., Ziegler I. Exp. Cell Res. 204:217-222(1993) [PubMed: 8440319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Salivary gland.
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[8]	"Genomic organization and chromosomal localization of the human sepiapterin reductase gene." Ohye T., Hori T.A., Katoh S., Nagatsu T., Ichinose H. Biochem. Biophys. Res. Commun. 251:597-602(1998) [PubMed: 9792819] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"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-213, MUTAGENESIS OF SER-213.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M76231 mRNA. Translation: AAA60314.1.
AK291856 mRNA. Translation: BAF84545.1.
AK222942 mRNA. Translation: BAD96662.1.
AC092630 Genomic DNA. Translation: AAY15035.1.
CH471053 Genomic DNA. Translation: EAW99757.1.
BC017310 mRNA. Translation: AAH17310.1.
AB017547 Genomic DNA. Translation: BAA34534.1.

IPI

IPI00017469.

PIR

JQ1176.

RefSeq

NP_003115.1.

UniGene

Hs.301540

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z6Z	X-ray	2.50	A/B/C/D/E/F	5-261	[»]

ModBase

Search...

PTM databases

PhosphoSite

P35270.

Proteomic databases

PeptideAtlas

P35270.

PRIDE

P35270.

Genome annotation databases

Ensembl

ENSG00000116096. Homo sapiens. [Contig view]

GeneID

6697.

KEGG

hsa:6697.

NMPDR

fig|9606.3.peg.18026.

Organism-specific databases

GeneCards

GC02P073026.

H-InvDB

HIX0002155.

HGNC

HGNC:11257. SPR.

MIM

182125. gene+phenotype.

Orphanet

70594. Motor and cognitive disorder due to sepiapterin reductase deficiency.

PharmGKB

PA36087.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P35270.

HOVERGEN

P35270.

OMA

P35270. SVDPDMR.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-13412.

BRENDA

1.1.1.153. 247.

Gene expression databases

ArrayExpress

P35270.

Bgee

P35270.

CleanEx

HS_SPR.

GermOnline

ENSG00000116096. Homo sapiens.

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

26111.

SOURCE

Search...

Entry information

Entry name

SPRE_HUMAN

Accession

Primary (citable) accession number: P35270
Secondary accession number(s): A8K741, Q53GI9, Q9UBB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	June 16, 2009
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)