Pyridoxine-5'-phosphate oxidase (PNPO)
The protein contains 261 amino acids for an estimated molecular weight of 29988 Da.
Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs549477447 | |
| dbSNP:rs17679445 | |
| PNPOD | |
| PNPOD | |
| PNPOD |
The reference OMIM entry for this protein is 603287
Pyridoxamine 5-prime-phosphate oxidase; pnpo
Pyridoxamine-phosphate oxidase
DESCRIPTION
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).CLONING
Ngo et al. (1998) isolated a PNPO clone from a rat liver library. They found that the predicted 30-kD protein contained the PNPO signature motif found in the PNPO of S. cerevisiae and bacteria and 5 predicted protein kinase C (see 176960) phosphorylation sites. Kang et al. (2004) cloned full-length PNPO from a whole brain cDNA library. The deduced 261-amino acid protein has a calculated molecular mass of 30 kD. Posttranslational modification sites include a sulfation site, 9 phosphorylation sites, 3 N-myristoylation sites, and an RGD cell attachment sequence. PNPO shares 90% amino acid identity with mouse Pnpo. Northern blot analysis detected transcripts of 2.4 and 3.4 kb in all human tissues examined, with the difference in transcript size due to use of alternative polyadenylation sites. Highest expression was in liver, followed by skeletal muscle and kidney. Western blot analysis detected a 30-kD protein in all tissues and cell lines examined.GENE FUNCTION
PNPO activity is developmentally regulated in rat liver, being low in fetal liver and high in adult liver. Ngo et al. (1998) showed that PNPO expression was similarly developmentally regulated in rat brain. Additionally, Ngo et al. (1998) demonstrated that, analogous to rodent hepatomas, PNPO expression in rodent brain tumors was comparable to or lower than that present in fetal rat brain. However, the human neuroblastoma cell lines examined displayed variable PNPO activity; a human hepatocellular carcinoma cell line contained relatively high PNPO activity, comparable to that found in normal human liver. Kang et al. (2004) characterized the enzymatic properties of recombinant PNPO following expression in E. coli. PNPO converted both PNP and pyridoxamine 5-prime-phosphate to PLP, and the PLP product was an inhibitor. Mutation analysis indicated that the first N-terminal conserved helix segment and the C-terminal 25 residues were required for enzymatic activity.GENE STRUCTURE
Kang et al. (2004) determined that the PNPO gene contains 7 exons and spans 7.7 kb. The promoter region shows characteristics of housekeeping genes, with a CpG island and Sp1 (189906)-binding sites, but no TATA-like sequences.MAPPING
By genomic sequence analysis, Kang et al. (2004) mapped the PNPO gene to chromosome 17q21.32. They mapped the mouse gene to chromosome 11.MOLECULAR GENETICS
In 5 patients from 3 families with PNPO deficiency (610090), Mills et al. (2005) identified homozygous missense, splice site, and stop codon mutations in the PNPO gene. Expression studies in Chinese hamster ovary cells showed that the splice site (IVS3-1G-A; 603287.0002) and stop codon (X262Q; 603287.0003) mutations were null activity mutations and that the missense mutation (R229W; 603287.0001) markedly reduced pyridox(am)ine phosphate oxidase activity. The authors suggested that maintenance of optimal PLP levels in the brain may be important in many neurologic disorders in which neurotransmitter metabolism is disturbed (either as a primary or as a secondary phenomenon). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603287 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed