Purine nucleoside phosphorylase

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Nucleoside phosphorylase

PDB rendering based on 1m73.

Available structures: 1m73, 1pf7, 1pwy, 1rct, 1rfg, 1rr6, 1rsz, 1rt9, 1ula, 1ulb, 1v2h, 1v3q, 1v41, 1v45, 1yry, 2a0w, 2a0x, 2a0y, 2oc4, 2oc9, 2on6

Identifiers

Symbol(s)

NP; MGC117396; MGC125915; MGC125916; PNP; PRO1837; PUNP

External IDs

OMIM: 164050 HomoloGene: 227

EC number

2.4.2.1

Gene ontology
Molecular Function:	• purine-nucleoside phosphorylase activity
Biological Process:	• nucleobase, nucleoside, nucleotide and nucleic acid metabolic process • DNA modification

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

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Refseq

NM_000270 (mRNA)
NP_000261 (protein)

n/a (mRNA)
n/a (protein)

Location

Chr 14: 20.01 - 20.02 Mb

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Pubmed search

[1]

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Purine nucleoside phosphorylase (also known as PNPase) is an enzyme (EC 2.4.2.1) involved in purine metabolism. PNP metabolizes adenosine into adenine, inosine into hypoxanthine, and guanosine into guanine, in each case creating ribose phosphate. NP encodes the enzyme purine nucleoside phosphorylase that together with adenosine deaminase (ADA) serves a key role in purine catabolism, referred to as the salvage pathway. Mutations in either enzyme result in a severe combined immunodeficiency (SCID).^[1] Confusingly, the same abbreviation (PNPase), is also used for another, otherwise unrelated, enzyme, namely Polynucleotide Phosphorylase.

Diseases linked to PNP: PNP deficient patients will have an immunodeficiency problem. Curiously, it affects only T-cells, B-cells are unaffected by the deficiency.

1 See also
2 References
3 Further reading
4 External links

[edit] See also

Purine nucleoside phosphorylase deficiency

[edit] References

^ Entrez Gene: NP nucleoside phosphorylase.

[edit] Further reading

Markert ML (1991). "Purine nucleoside phosphorylase deficiency.". Immunodeficiency reviews 3 (1): 45–81. PMID 1931007.
Borgers M, Verhaegen H, De Brabander M, et al. (1978). "Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL).". Blood 52 (5): 886–95. PMID 100152.
Aust MR, Andrews LG, Barrett MJ, et al. (1992). "Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency.". Am. J. Hum. Genet. 51 (4): 763–72. PMID 1384322.
Andrews LG, Markert ML (1992). "Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency.". J. Biol. Chem. 267 (11): 7834–8. PMID 1560016.
Jonsson JJ, Williams SR, McIvor RS (1991). "Sequence and functional characterization of the human purine nucleoside phosphorylase promoter.". Nucleic Acids Res. 19 (18): 5015–20. PMID 1923769.
Ealick SE, Rule SA, Carter DC, et al. (1990). "Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution.". J. Biol. Chem. 265 (3): 1812–20. PMID 2104852.
Williams SR, Gekeler V, McIvor RS, Martin DW (1987). "A human purine nucleoside phosphorylase deficiency caused by a single base change.". J. Biol. Chem. 262 (5): 2332–8. PMID 3029074.
Williams SR, Goddard JM, Martin DW (1984). "Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization.". Nucleic Acids Res. 12 (14): 5779–87. PMID 6087295.
Pannicke U, Tuchschmid P, Friedrich W, et al. (1997). "Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient.". Hum. Genet. 98 (6): 706–9. PMID 8931706.
Markert ML, Finkel BD, McLaughlin TM, et al. (1997). "Mutations in purine nucleoside phosphorylase deficiency.". Hum. Mutat. 9 (2): 118–21. doi:10.1002/(SICI)1098-1004(1997)9:2<118::AID-HUMU3>3.0.CO;2-5. PMID 9067751.
Erion MD, Takabayashi K, Smith HB, et al. (1997). "Purine nucleoside phosphorylase. 1. Structure-function studies.". Biochemistry 36 (39): 11725–34. doi:10.1021/bi961969w. PMID 9305962.
Erion MD, Stoeckler JD, Guida WC, et al. (1997). "Purine nucleoside phosphorylase. 2. Catalytic mechanism.". Biochemistry 36 (39): 11735–48. doi:10.1021/bi961970v. PMID 9305963.
Stoeckler JD, Poirot AF, Smith RM, et al. (1997). "Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis.". Biochemistry 36 (39): 11749–56. doi:10.1021/bi961971n. PMID 9305964.
Sasaki Y, Iseki M, Yamaguchi S, et al. (1998). "Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient.". Hum. Genet. 103 (1): 81–5. PMID 9737781.
Sheppard TL, Ordoukhanian P, Joyce GF (2000). "A DNA enzyme with N-glycosylase activity.". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 7802–7. PMID 10884411.
Dalal I, Grunebaum E, Cohen A, Roifman CM (2001). "Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.". Clin. Genet. 59 (6): 430–7. PMID 11453975.
Ivings L, Pennington SR, Jenkins R, et al. (2002). "Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin.". Biochem. J. 363 (Pt 3): 599–608. PMID 11964161.
Falkenberg M, Gaspari M, Rantanen A, et al. (2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA.". Nat. Genet. 31 (3): 289–94. doi:10.1038/ng909. PMID 12068295.
Stoychev G, Kierdaszuk B, Shugar D (2002). "Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems.". Eur. J. Biochem. 269 (16): 4048–57. PMID 12180982.

[edit] External links

v • d • e Transferases: glycosyltransferases (EC 2.4)

2.4.1 - Hexosyltransferases: glucosyltransferase	Phosphorylase (Starch, Glycogen, Myo-) - Glycogen synthase - Debranching enzyme - Branching enzyme - 1,3-beta-glucan synthase - Ceramide glucosyltransferase

2.4.1 - Hexosyltransferases: other	Galactosyltransferase (Lactose synthase, B-N-acetylglucosaminyl-glycopeptide b-1,4-galactosyltransferase) Glucuronosyltransferase (UGT1A1, UGT2B7, Hyaluronan synthase) Fucosyltransferase (POFUT1, POFUT2)

2.4.2 - Pentosyltransferases: ADP ribose	Cholera toxin - Diphtheria toxin - Pertussis toxin - Poly ADP ribose polymerase

2.4.2 - Pentosyltransferases: other	Purine nucleoside phosphorylase - Adenine phosphoribosyltransferase - Hypoxanthine-guanine phosphoribosyltransferase - Uracil phosphoribosyltransferase - Amidophosphoribosyltransferase - Xylosyltransferase

v • d • e

Metabolism: amino acid metabolism - nucleotide enzymes

Purine metabolism

Anabolism	synthesis: Amidophosphoribosyltransferase - Inosine monophosphate synthase GMP (IMP dehydrogenase, GMP synthase, GMP reductase) AMP (Adenylosuccinate synthase, Adenylosuccinate lyase, AMP deaminase)

Nucleotide salvage	Hypoxanthine-guanine phosphoribosyltransferase - Adenine phosphoribosyltransferase

Catabolism	Adenosine deaminase - Purine nucleoside phosphorylase - Guanine deaminase - Xanthine oxidase - Urate oxidase

Pyrimidine metabolism

Anabolism	CAD (Carbamoyl phosphate synthase II, Aspartate carbamoyltransferase, Dihydroorotase) Dihydroorotate dehydrogenase - Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase CTP synthase

Catabolism	Dihydropyrimidine dehydrogenase - Dihydropyrimidinase/DPYS - Beta-ureidopropionase/UPB1