Description: Homo sapiens hypoxanthine phosphoribosyltransferase 1 (HPRT1), mRNA. RefSeq Summary (NM_000194): The protein encoded by this gene is a transferase, which catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. This enzyme plays a central role in the generation of purine nucleotides through the purine salvage pathway. Mutations in this gene result in Lesch-Nyhan syndrome or gout.[provided by RefSeq, Jun 2009]. Transcript (Including UTRs) Position: hg19 chrX:133,594,175-133,634,698 Size: 40,524 Total Exon Count: 9 Strand: + Coding Region Position: hg19 chrX:133,594,342-133,634,107 Size: 39,766 Coding Exon Count: 9
ID:HPRT_HUMAN DESCRIPTION: RecName: Full=Hypoxanthine-guanine phosphoribosyltransferase; Short=HGPRT; Short=HGPRTase; EC=2.4.2.8; FUNCTION: Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5- phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway. CATALYTIC ACTIVITY: IMP + diphosphate = hypoxanthine + 5-phospho- alpha-D-ribose 1-diphosphate. CATALYTIC ACTIVITY: GMP + diphosphate = guanine + 5-phospho-alpha- D-ribose 1-diphosphate. COFACTOR: Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.4 uM for IMP; KM=0.45 uM for hypoxanthine; KM=25 uM for pyrophosphate; KM=31 uM for phosphoribosylpyrophosphate; PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1. SUBUNIT: Homotetramer. INTERACTION: Q96HA8:WDYHV1; NbExp=3; IntAct=EBI-748210, EBI-741158; SUBCELLULAR LOCATION: Cytoplasm. DISEASE: Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:300322]. LNS is characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation. DISEASE: Defects in HPRT1 are the cause of gout HPRT-related (GOUT-HPRT) [MIM:300323]; also known as HPRT-related gout or Kelley-Seegmiller syndrome. Gout is characterized by partial enzyme activity and hyperuricemia. SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HPRT1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/hprt1/"; WEB RESOURCE: Name=Wikipedia; Note=Hypoxanthine-guanine phosphoribosyltransferase entry; URL="http://en.wikipedia.org/wiki/Hypoxanthine-guanine_phosphoribosyltransferase";
cytogenetic studies Perera, F. et al. 2002, In utero DNA damage from environmental pollution is associated with somatic gene mutation in newborns., Cancer epidemiology, biomarkers & prevention. 2002 Oct;11(10 Pt 1):1134-7.
[PubMed 12376523]
These results provide the first demonstration of a molecular link between somatic mutation in the newborn and transplacental exposure to common air pollutants, a finding that is relevant to cancer risk assessment.
Lesch-Nyhan syndrome Mizunuma M et al. 2001, A recurrent large Alu-mediated deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene associated with Lesch-Nyhan syndrome., Human mutation. 2001 Nov;18(5):435-43.
[PubMed 11668636]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00492
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00230 - Purine metabolism hsa00983 - Drug metabolism - other enzymes hsa01100 - Metabolic pathways
BioCyc Knowledge Library P1-PWY - purine and pyrimidine metabolism PWY-6599 - guanine and guanosine salvage II PWY-6609 - adenine and adenosine salvage III
Reactome (by CSHL, EBI, and GO)
Protein P00492 (Reactome details) participates in the following event(s):