Q9NVS9 (PNPO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyridoxine-5'-phosphate oxidase
EC=1.4.3.5

Alternative name(s):
Pyridoxamine-phosphate oxidase

Gene names

Name:

PNPO

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.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP). Ref.7
Catalytic activity	Pyridoxamine 5'-phosphate + H2O + O2 = pyridoxal 5'-phosphate + NH3 + H2O2. Pyridoxine 5'-phosphate + O2 = pyridoxal 5'-phosphate + H2O2.
Cofactor	Binds 1 FMN per subunit.
Pathway	Cofactor biosynthesis; B6 vitamer interconversion; pyridoxal 5'-phosphate from pyridoxamine 5'-phosphate: step 1/1. Cofactor biosynthesis; B6 vitamer interconversion; pyridoxal 5'-phosphate from pyridoxine 5'-phosphate: step 1/1.
Subunit structure	Homodimer. Ref.7
Involvement in disease	Defects in PNPO are the cause of pyridoxine-5'-phosphate oxidase deficiency (PNPO deficiency) [MIM:610090]; also known as PNPO-related neonatal epileptic encephalopathy. The main feature of neonatal epileptic encephalopathy is the onset within hours of birth of a severe seizure disorder that does not respond to anticonvulsant drugs and can be fatal. Seizures can cease with the administration of PLP, being resistant to treatment with pyridoxine.
Sequence similarities	Belongs to the pyridoxamine 5'-phosphate oxidase family.

Ontologies

Keywords
Biological process	Pyridoxine biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy
Ligand	FMN Flavoprotein Pyridoxal phosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	pyridoxine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	FMN binding Inferred from electronic annotation. Source: InterPro pyridoxamine-phosphate oxidase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 261

261

Pyridoxine-5'-phosphate oxidase

PRO_0000167783

Regions

Nucleotide binding

110 – 111

2

FMN

Nucleotide binding

174 – 175

2

FMN

Region

225 – 227

3

Substrate binding

Sites

Binding site

95

1

FMN

Binding site

98

1

FMN; via amide nitrogen

Binding site

100

1

Substrate

Binding site

117

1

FMN

Binding site

157

1

Substrate

Binding site

161

1

Substrate

Binding site

165

1

Substrate

Amino acid modifications

Modified residue

40

1

Phosphoserine Ref.5

Modified residue

165

1

Phosphoserine By similarity

Modified residue

241

1

Phosphoserine By similarity

Natural variations

Natural variant

50

1

E → K. Ref.8

VAR_029358

Natural variant

116

1

R → Q.
Corresponds to variant rs17679445 [ dbSNP | Ensembl ].

VAR_029359

Natural variant

229

1

R → W in PNPO deficiency; strong activity decrease. Ref.8

VAR_029360

Secondary structure

1

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261

Helix Strand Turn

Details...

Helix

58 – 71

14

Beta strand

80 – 86

7

Beta strand

92 – 98

7

Beta strand

106 – 112

7

Helix

116 – 123

8

Beta strand

126 – 133

8

Helix

134 – 136

3

Beta strand

138 – 148

11

Helix

151 – 160

10

Helix

163 – 171

9

Beta strand

176 – 179

4

Helix

181 – 194

14

Turn

195 – 197

3

Beta strand

206 – 211

6

Beta strand

214 – 220

7

Beta strand

228 – 234

7

Beta strand

254 – 259

6

Sequences

	Sequence		Length	Mass (Da)
	Q9NVS9 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 2C74E9F962FE2A95	FASTA	261	29,988
	10 20 30 40 50 60 MTCWLRGVTA TFGRPAEWPG YLSHLCGRSA AMDLGPMRKS YRGDREAFEE THLTSLDPVK 70 80 90 100 110 120 QFAAWFEEAV QCPDIGEANA MCLATCTRDG KPSARMLLLK GFGKDGFRFF TNFESRKGKE 130 140 150 160 170 180 LDSNPFASLV FYWEPLNRQV RVEGPVKKLP EEEAECYFHS RPKSSQIGAV VSHQSSVIPD 190 200 210 220 230 240 REYLRKKNEE LEQLYQDQEV PKPKSWGGYV LYPQVMEFWQ GQTNRLHDRI VFRRGLPTGD 250 260 SPLGPMTHRG EEDWLYERLA P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Kwon O.-S. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"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: Teratocarcinoma.
[3]	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].
[4]	"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: Lymph.
[5]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase." Musayev F.N., Di Salvo M.L., Ko T.-P., Schirch V., Safo M.K. Protein Sci. 12:1455-1463(2003) [PubMed: 12824491] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 49-161 IN COMPLEX WITH FMN AND PYRIDOXAL 5'-PHOSPHATE, PARTIAL PROTEIN SEQUENCE, SUBUNIT, ENZYME REGULATION, FUNCTION.
[8]	"Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase." Mills P.B., Surtees R.A.H., Champion M.P., Beesley C.E., Dalton N., Scambler P.J., Heales S.J.R., Briddon A., Scheimberg I., Hoffmann G.F., Zschocke J., Clayton P.T. Hum. Mol. Genet. 14:1077-1086(2005) [PubMed: 15772097] [Abstract] Cited for: VARIANT PNPO DEFICIENCY TRP-229, VARIANT LYS-50.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF468030 mRNA. Translation: AAM76918.1.
AK001397 mRNA. Translation: BAA91668.1.
CH471109 Genomic DNA. Translation: EAW94770.1.
CH471109 Genomic DNA. Translation: EAW94771.1.
BC006525 mRNA. Translation: AAH06525.1.

IPI

IPI00018272.

RefSeq

NP_060599.1. NM_018129.3.

UniGene

Hs.631742.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NRG	X-ray	1.95	A	1-261	[»]
3HY8	X-ray	2.50	A	1-261	[»]

ProteinModelPortal

Q9NVS9.

SMR

Q9NVS9. Positions 49-261.

DisProt

DP00168.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9NVS9.

PTM databases

PhosphoSite

Q9NVS9.

Polymorphism databases

DMDM

37082126.

2D gel databases

REPRODUCTION-2DPAGE

IPI00018272.

Proteomic databases

PeptideAtlas

Q9NVS9.

PRIDE

Q9NVS9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225573; ENSP00000225573; ENSG00000108439.

GeneID

55163.

KEGG

hsa:55163.

NMPDR

fig|9606.3.peg.13977.

UCSC

uc002imo.1. human.

Organism-specific databases

CTD

55163.

GeneCards

GC17P046018.

H-InvDB

HIX0013929.

HGNC

HGNC:30260. PNPO.

HPA

HPA023204.
HPA027776.

MIM

603287. gene.
610090. phenotype.

neXtProt

NX_Q9NVS9.

Orphanet

79096. Pyridoxal phosphate-responsive seizures.

PharmGKB

PA134915565.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000011219.

HOGENOM

HBG327559.

HOVERGEN

HBG045634.

InParanoid

Q9NVS9.

OMA

FTFFTNY.

OrthoDB

EOG4CVG7G.

PhylomeDB

Q9NVS9.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9NVS9.

Bgee

Q9NVS9.

CleanEx

HS_PNPO.

Genevestigator

Q9NVS9.

GermOnline

ENSG00000108439. Homo sapiens.

Family and domain databases

InterPro

IPR000659. Pyridox_Oxase.
IPR019740. Pyridox_Oxase_CS.
IPR011576. Pyridox_Oxase_FMN-bd.
IPR019576. Pyridoxamine_oxidase_dimer_C.
IPR012349. Split_barrel_FMN-bd.
IPR009002. Split_barrel_FMN-bd-related.
[Graphical view]

Gene3D

G3DSA:2.30.110.10. PNPOx_FMN_bd. 1 hit.

KO

K00275.

PANTHER

PTHR10851. Pyridox_oxidase. 1 hit.

Pfam

PF10590. PNPOx_C. 1 hit.
PF01243. Pyridox_oxidase. 1 hit.
[Graphical view]

PIRSF

PIRSF000190. Pyd_amn-ph_oxd. 1 hit.

SUPFAM

SSF50475. FMN_binding. 1 hit.

TIGRFAMs

TIGR00558. PdxH. 1 hit.

PROSITE

PS01064. PYRIDOX_OXIDASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00114. Pyridoxal Phosphate.

NextBio

58925.

SOURCE

Search...

Entry information

Entry name

PNPO_HUMAN

Accession

Primary (citable) accession number: Q9NVS9
Secondary accession number(s): D3DTT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.