Nucleoside phosphorylase

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It has been suggested that Purine nucleoside phosphorylase be merged into this article or section. (Discuss)

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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Nucleoside phosphorylase, also known as NP, is a human gene.^[1]

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]

Nucleoside phosphorylase is an enzyme which, as its name implies, phosphorylates a nucleoside to produce a nucleotide monophosphate. It is one enzyme of the nucleotide salvage pathways. These pathways allow the cell to produce nucleotide monophosphates when the de novo synthesis pathway has been interrupted or is non-existent (as is the case in the brain). Often the de novo pathway is interrupted as a result of chemotherapy drugs such as methotrexate or aminopterin.

All salvage pathway enzymes require a high energy phosphate donor such as ATP or PRPP.

Thymidine can be phosphorylated by thymidine kinase (TK).
Uridine can be phosphorylated by uridine kinase (UK).
Cytidine can be phosphorylated by cytidine kinase (CK).
Deoxycytidine can be phosphorylated by deoxycytidine kinase (DOK).

Adenosine uses the enzyme adenosine kinase, which is a very important enzyme in the cell. Attempts are being made to develop an inhibitor for the enzyme for use in cancer chemotherapy.

[edit] See also

Purine nucleoside phosphorylase

[edit] References

^ ^a ^b 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.