Purine nucleoside phosphorylase (PNP)
The protein contains 289 amino acids for an estimated molecular weight of 32118 Da.
Catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:9305964, PubMed:23438750). Preferentially acts on 6-oxopurine nucleosides including inosine and guanosine (PubMed:9305964). (updated: Feb. 10, 2021)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
Biological Process
DAMP catabolic process
Immune response
IMP catabolic process
Inosine catabolic process
Interleukin-2 production
Interleukin-2 secretion
NAD biosynthesis via nicotinamide riboside salvage pathway
Neutrophil degranulation
Nicotinamide riboside catabolic process
Nucleobase-containing compound metabolic process
Nucleobase-containing small molecule metabolic process
Nucleotide biosynthetic process
Positive regulation of alpha-beta T cell differentiation
Positive regulation of interleukin-2 production
Positive regulation of T cell proliferation
Purine nucleobase metabolic process
Purine nucleotide catabolic process
Purine ribonucleoside salvage
Purine-containing compound salvage
Response to drug
Small molecule metabolic process
Urate biosynthetic process
The reference OMIM entry for this protein is 164050
Purine nucleoside phosphorylase; pnp
Nucleoside phosphorylase; np
Purine-nucleoside:orthophosphate ribosyltransferase
DESCRIPTION
The PNP gene encodes purine nucleoside phosphorylase (EC 2.4.2.1), an enzyme that catalyzes the reversible phosphorolysis of the purine nucleosides and deoxynucleosides inosine, guanosine, deoxyinosine, and deoxyguanosine (Williams et al., 1984).CLONING
Zannis et al. (1978) and Williams et al. (1984) demonstrated that human PNP is a symmetric trimer composed of 3 identical 32,153-Da subunits, each with a substrate-binding site. PNP encodes a deduced protein of 289 amino acids.MAPPING
From the findings in somatic cell hybridization studies, nucleoside phosphorylase is known to be determined by a structural locus on chromosome 14. In a classic experiment using the KOP (Kirby-Opitz-Pallister) cell line carrying an X;14 translocation (GM73 and GM74), Ricciuti and Ruddle (1973) showed that the PNP locus is on chromosome 14 (and G6PD (305900) on distal Xq). In hybridization experiments with t(X;14)(p22;q21), Francke et al. (1976) found that the PNP locus is proximal to 14q22. Using gene dosage effect and 4 cases of different partial trisomy of chromosome 14, George and Francke (1976) narrowed the assignment of PNP to the region 14q11-q21. Frecker et al. (1978) presented results from gene dosage studies consistent with assignment of the PNP locus to band 14q13. Allderdice et al. (1978) investigated spreading of inactivation in the KOP translocation originally used in mapping PNP to 14q. Remes et al. (1984) presented additional deletion mapping data that they interpreted, in the light of earlier findings, as narrowing the SRO for PNP to 14q12.00-q13.105. The location was placed at 14q13.1. The evidence of Harper et al. (1988) indicated that the PNP gene is located centromeric to TCRA (see 186880). HGM10 concluded that PNP is located in the 14q11.2 band.MOLECULAR GENETICS
Edwards et al. (1971) described electrophoretic variants of nucleoside phosphorylase. Family studies indicated autosomal codominant inheritance of the variants. In a patient with nucleoside phosphorylase deficiency (613179), Williams et al. (1987) identified a homozygous mutation in the PNP gene (E89K; 164050.0001). Aust et al. (1992) identified compound heterozygosity for 2 mutations in the PNP gene (D128G, 164050.0003; R234P, 164050.0004) in a patient with nucleoside phosphorylase deficiency. In a patient with PNP deficiency, Dalal et al. (2001) identified compound heterozygosity for 2 mutations in the PNP gene (164050.0009; 164050.0010).ANIMAL MODEL
By male germ cell mutagenesis, Snyder et al. (1997) recovered 3 point mutations in the Pnp gene. These were, in order of increasing order of severity of enzyme deficiency and phenotype, met87 to lys, ala228 to thr, and trp16 to arg. A marked decline in total cell numbers per thymus occurred between 2 and 3 months for the 2 more severe mutants (35% and 52%, respectively) and by 8 months for the least severe mutation. Spleen lymphocyte Thy-1(+) cells were reduced by 50% and spleen lymphocyte response to T-cell mitogen and interleukin-2 was reduced by 80%. The Pnp-deficient mouse exhibited age-dependent progressive perturbations in thymocyte differentiation, reduced numbers of thymocytes, and reduced splenic T-cell numbers and response. The progressive T-cell deficit was similar to that observed in the human disorder. ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PNP
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 164050 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed