Adenine phosphoribosyltransferase

Adenine phosphoribosyltransferase
Ribbon diagram of a human APRT dimer, in complex with PRPP, adenine and ribose 5-phosphate. One magnesium ion visible in green. From PDB 1ZN7.
Available structures PDB 1OPU, 1ORE, 1ZN7, 1ZN8, 1ZN9
Identifiers
Symbols	APRT; AMP; DKFZp686D13177; MGC125856; MGC125857; MGC129961
External IDs	OMIM: 102600 MGI: 88061 HomoloGene: 413 GeneCards: APRT Gene
EC number	2.4.2.7
Gene Ontology Molecular function • adenine binding • adenine phosphoribosyltransferase activity • protein binding • AMP binding • transferase activity, transferring glycosyl groups Cellular component • nucleus • nucleolus • cytoplasm • cytoplasm • cytosol Biological process • purine base metabolic process • purine ribonucleoside salvage • adenine salvage • grooming behavior • nucleoside metabolic process • purine-containing compound salvage • adenine metabolic process • nucleobase, nucleoside and nucleotide metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	353	11821
Ensembl	ENSG00000198931	ENSMUSG00000006589
UniProt	P07741	Q564P4
RefSeq (mRNA)	NM_000485.2	NM_009698.2
RefSeq (protein)	NP_000476.1	NP_033828.2
Location (UCSC)	Chr 16: 88.88 – 88.88 Mb	Chr 8: 125.1 – 125.1 Mb
PubMed search	[1]	[2]

Adenine phosphoribosyltransferase is an enzyme that in humans is encoded by the APRT gene.

Function

APRTase is an enzyme involved in the purine nucleotide salvage pathway. It functions as a catalyst in the reaction between adenine and phosphoribosyl pyrophosphate (PRPP) to form AMP.

APRT is functionally related to hypoxanthine-guanine phosphoribosyltransferase (HPRT).

Pathology

Deficiency of APRT in human beings may lead to kidney stones formed of adenine and salts.

2,8-Dihydroxy-adenine urolithiasis is also known as "adenine phosphoribosyltransferase deficiency".

Adenine phosphoribosyltransferase (APRT) deficiency is an uncommon genetic disorder that often causes kidney stones, and in some patients kidney failure. More than 300 individuals with this disease have been reported world-wide but it is not known how common this medical problem truly is. Patients with the disease deficiency lack the enzyme adenine phosphoribosyltransferase and therefore have difficulties breaking down dietary substances called purines, resulting in accumulation of a compound called 2,8-dihydroxyadenine (2,8-DHA) that is excreted by the kidneys. 2,8-DHA is poorly soluble in the urine leads to the formation of kidney stones and kidney injury. Interestingly, up to 70% of affected patients, have red hair or relatives with this hair color.

Further reading

• Tischfield JA, Engle SJ, Gupta PK, et al. (1995). "Germline and somatic mutation at the APRT locus of mice and man.". Adv. Exp. Med. Biol. 370: 661–4. PMID 7660991. 
• Takeuchi H, Kaneko Y, Fujita J, Yoshida O (1993). "A case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis: review of the reported cases with 2,8-dihydroxyadenine stones in Japan.". J. Urol. 149 (4): 824–6. PMID 8455250. 
• Ludwig H, Kuzmits R, Pietschmann H, Müller MM (1980). "Enzymes of the purine interconversion system in chronic lymphatic leukemia: decreased purine nucleoside phosphorylase and adenosine deaminase activity.". Blut 39 (5): 309–15. doi:10.1007/BF01014193. PMID 116697. 
• Johnson LA, Gordon RB, Emmerson BT (1977). "Adenine phosphoribosyltransferase: a simple spectrophotometric assay and the incidence of mutation in the normal population.". Biochem. Genet. 15 (3–4): 265–72. doi:10.1007/BF00484458. PMID 869896. 
• Kamatani N, Hakoda M, Otsuka S, et al. (1992). "Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients". J. Clin. Invest. 90 (1): 130–5. doi:10.1172/JCI115825. PMC 443071. PMID 1353080. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=443071. 
• Chen J, Sahota A, Laxdal T, et al. (1992). "Identification of a single missense mutation in the adenine phosphoribosyltransferase (APRT) gene from five Icelandic patients and a British patient". Am. J. Hum. Genet. 49 (6): 1306–11. PMC 1686459. PMID 1746557. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1686459. 
• Mimori A, Hidaka Y, Wu VC, et al. (1991). "A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects". Am. J. Hum. Genet. 48 (1): 103–7. PMC 1682758. PMID 1985452. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1682758. 
• Chen J, Sahota A, Stambrook PJ, Tischfield JA (1991). "Polymerase chain reaction amplification and sequence analysis of human mutant adenine phosphoribosyltransferase genes: the nature and frequency of errors caused by Taq DNA polymerase". Mutat. Res. 249 (1): 169–76. doi:10.1016/0027-5107(91)90143-C. PMID 2067530. 
• Gathof BS, Sahota A, Gresser U, et al. (1992). "Identification of a splice mutation at the adenine phosphoribosyltransferase locus in a German family". Klin. Wochenschr. 69 (24): 1152–5. doi:10.1007/BF01815434. PMID 2135300. 
• Kamatani N, Kuroshima S, Hakoda M, et al. (1990). "Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation". Hum. Genet. 85 (6): 600–4. doi:10.1007/BF00193582. PMID 2227951. 
• Kamatani N, Kuroshima S, Terai C, et al. (1989). "Detection of an amino acid substitution in the mutant enzyme for a special type of adenine phosphoribosyltransferase (APRT) deficiency by sequence-specific protein cleavage". Am. J. Hum. Genet. 45 (2): 325–31. PMC 1683345. PMID 2502918. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683345. 
• Hidaka Y, Tarlé SA, Fujimori S, et al. (1988). "Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese". J. Clin. Invest. 81 (3): 945–50. doi:10.1172/JCI113408. PMC 442550. PMID 3343350. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442550. 
• Wilson JM, O'Toole TE, Argos P, et al. (1986). "Human adenine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme". J. Biol. Chem. 261 (29): 13677–83. PMID 3531209. 
• Broderick TP, Schaff DA, Bertino AM, et al. (1987). "Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement". Proc. Natl. Acad. Sci. U.S.A. 84 (10): 3349–53. doi:10.1073/pnas.84.10.3349. PMC 304867. PMID 3554238. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=304867. 
• Hidaka Y, Palella TD, O'Toole TE, et al. (1987). "Human adenine phosphoribosyltransferase. Identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme". J. Clin. Invest. 80 (5): 1409–15. doi:10.1172/JCI113219. PMC 442397. PMID 3680503. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442397. 
• Hidaka Y, Tarlé SA, O'Toole TE, et al. (1988). "Nucleotide sequence of the human APRT gene". Nucleic Acids Res. 15 (21): 9086. doi:10.1093/nar/15.21.9086. PMC 306432. PMID 3684585. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=306432. 
• Chen J, Sahota A, Martin GF, et al. (1993). "Analysis of germline and in vivo somatic mutations in the human adenine phosphoribosyltransferase gene: mutational hot spots at the intron 4 splice donor site and at codon 87". Mutat. Res. 287 (2): 217–25. doi:10.1016/0027-5107(93)90014-7. PMID 7685481. 
• Sahota A, Chen J, Boyadjiev SA, et al. (1994). "Missense mutation in the adenine phosphoribosyltransferase gene causing 2,8-dihydroxyadenine urolithiasis". Hum. Mol. Genet. 3 (5): 817–8. doi:10.1093/hmg/3.5.817. PMID 7915931. 

External links

• MeSH Adenine+phosphoribosyltransferase