Hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine phosphoribosyltransferase 1
Ribbon diagram of a human HPRT tetramer. Magnesium ions visible in green. From PDB: 1BZY​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BZY, 1D6N, 1HMP, 1Z7G, 2VFA, 3GEP, 3GGC, 3GGJ, 4IJQ, 4KN6, 4RAB, 4RAC, 4RAD, 4RAN, 4RAO, 4RAQ
Identifiers
Symbols	HPRT1 ; HGPRT; HPRT
External IDs	OMIM: 308000 MGI: 96217 HomoloGene: 56590 ChEMBL: 2360 GeneCards: HPRT1 Gene
EC number	2.4.2.8
Gene ontology Molecular function • nucleotide binding • magnesium ion binding • hypoxanthine phosphoribosyltransferase activity • protein binding • protein homodimerization activity • guanine phosphoribosyltransferase activity Cellular component • cytoplasm • cytosol • extracellular exosome Biological process • response to amphetamine • purine nucleobase metabolic process • purine nucleotide biosynthetic process • purine ribonucleoside salvage • adenine salvage • guanine salvage • grooming behavior • locomotory behavior • cytolysis • striatum development • cerebral cortex neuron differentiation • central nervous system neuron development • GMP salvage • IMP salvage • dopamine metabolic process • purine-containing compound salvage • hypoxanthine salvage • small molecule metabolic process • positive regulation of dopamine metabolic process • GMP catabolic process • IMP metabolic process • hypoxanthine metabolic process • lymphocyte proliferation • dendrite morphogenesis • protein homotetramerization • nucleobase-containing small molecule metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3251	15452
Ensembl	ENSG00000165704	ENSMUSG00000025630
UniProt	P00492	P00493
RefSeq (mRNA)	NM_000194	NM_013556
RefSeq (protein)	NP_000185	NP_038584
Location (UCSC)	Chr X: 134.46 – 134.52 Mb	Chr X: 52.99 – 53.02 Mb
PubMed search	[1]	[2]

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme encoded in humans by the HPRT1 gene.

HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate (PRPP) to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Function

hypoxanthine phosphoribosyltransferase
Identifiers
EC number	2.4.2.8
CAS number	Template:CAS
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

HGPRT catalyzes the following reactions:

Substrate	Product	Notes
hypoxanthine	inosine monophosphate	—
guanine	guanosine monophosphate	Often called HGPRT. Performs this function only in some species.
xanthine	xanthosine monophosphate	Only certain HPRTs.

HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) to form inosine monophosphate.

Substrates and inhibitors

Comparative homology modelling of this enzyme in L. donovani suggest that among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate). The in silico and in-vitro correlation of these compounds were test in Leishmania HGPRT and validates the result.

Role in disease

Mutations in the gene lead to hyperuricemia:

• Some men have partial (up to 20% less activity of the enzyme) HGPRT deficiency that causes high levels of uric acid in the blood, which leads to the development of gouty arthritis and the formation of uric acid stones in the urinary tract. This condition has been named the Kelley-Seegmiller syndrome.
• Lesch-Nyhan syndrome is due to deficiency of HGPRT caused by HPRT1 mutation
• Some mutations have been linked to gout, the risk of which is increased in hypoxanthine-guanine phosphoribosyltransferase deficiency.
• HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 (HIF1A). HIF-1 is a transcription factor that directs an array of cellular responses that are used for adaptation during oxygen deprivation. This finding implies that HPRT is a critical pathway that helps preserve the cell's purine nucleotide resources under hypoxic conditions as found in pathology such as myocardial ischemia.

Hybridomas

Hybridomas are immortal (immune to cellular senescence), HGPRT⁺ cells that result from fusion of mortal, HGPRT⁺ plasma cells and immortal, HGPRT⁻ myeloma cells. They are created to produce monoclonal antibodies in biotechnology. HAT medium inhibits de novo synthesis of nucleic acids, killing myelomas that cannot switch over to salvage pathway, due to lack of HRPT1. Plasma cells eventually die from senesence, leaving pure hybridoma cells.

See also

• Nucleotide salvage

External links

• Hypoxanthine phosphoribosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Purine metabolism at genome.jp
• GeneReviews/NCBI/NIH/UW entry on Lesch-Nyhan Syndrome