PNPO

Pyridoxine-5'-phosphate oxidase is an enzyme that in humans is encoded by the PNPO gene.[5][6][7]

PNPO
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NRG, 3HY8
Identifiers
Aliases	PNPO, HEL-S-302, PDXPO, pyridoxamine 5'-phosphate oxidase
External IDs	OMIM: 603287 MGI: 2144151 HomoloGene: 5364 GeneCards: PNPO
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.32 Start 47,941,506 bp[1] End 47,949,308 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 D Start 96,937,825 bp[2] End 96,943,986 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • oxidoreductase activity • oxidoreductase activity, acting on the CH-NH2 group of donors • GO:0001948 protein binding • pyridoxamine-phosphate oxidase activity • FMN binding • pyridoxal phosphate binding • protein homodimerization activity Cellular component • nucleoplasm • cytosol Biological process • pyridoxine biosynthetic process • vitamin B6 metabolic process • oxidation-reduction process • pyridoxal phosphate biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55163	103711
Ensembl	ENSG00000108439	ENSMUSG00000018659
UniProt	Q9NVS9	Q91XF0
RefSeq (mRNA)	NM_018129	NM_134021
RefSeq (protein)	NP_060599	NP_598782
Location (UCSC)	Chr 17: 47.94 – 47.95 Mb	Chr 11: 96.94 – 96.94 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Vitamin B₆, or pyridoxal 5-prime-phosphate (PLP), is critical for normal cellular function, and some cancer cells have notable differences in vitamin B₆ metabolism compared to their normal counterparts. The rate-limiting enzyme in vitamin B₆ synthesis is pyridoxine-5-prime-phosphate (PNP) oxidase (PNPO; EC 1.4.3.5).[supplied by OMIM][7]

Model organisms

Pnpo knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[8]
Citrobacter infection	Normal[9]
All tests and analysis from[10][11]

Model organisms have been used in the study of PNPO function. A conditional knockout mouse line, called Pnpo^{tm1a(KOMP)Wtsi}[12][13] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.[10] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000108439 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018659 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ngo EO, LePage GR, Thanassi JW, Meisler N, Nutter LM (Jun 1998). "Absence of pyridoxine-5'-phosphate oxidase (PNPO) activity in neoplastic cells: isolation, characterization, and expression of PNPO cDNA". Biochemistry. 37 (21): 7741–8. doi:10.1021/bi972983r. PMID 9601034.
6. Kang JH, Hong ML, Kim DW, Park J, Kang TC, Won MH, Baek NI, Moon BJ, Choi SY, Kwon OS (Jun 2004). "Genomic organization, tissue distribution and deletion mutation of human pyridoxine 5'-phosphate oxidase". Eur J Biochem. 271 (12): 2452–61. doi:10.1111/j.1432-1033.2004.04175.x. PMID 15182361.
7. "Entrez Gene: PNPO pyridoxamine 5'-phosphate oxidase".
8. "Salmonella infection data for Pnpo". Wellcome Trust Sanger Institute.
9. "Citrobacter infection data for Pnpo". Wellcome Trust Sanger Institute.
10. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
12. "International Knockout Mouse Consortium".
13. "Mouse Genome Informatics".
14. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
15. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
16. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Musayev FN, Di Salvo ML, Ko TP, et al. (2004). "Structure and properties of recombinant human pyridoxine 5′-phosphate oxidase". Protein Sci. 12 (7): 1455–63. doi:10.1110/ps.0356203. PMC 2323923. PMID 12824491.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Mills PB, Surtees RA, Champion MP, et al. (2005). "Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase". Hum. Mol. Genet. 14 (8): 1077–86. doi:10.1093/hmg/ddi120. PMID 15772097.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.