PRPS1 Products

Description

Ribose-phosphate pyrophosphokinase 1 (PRPS1), also known as phosphoribosyl pyrophosphate synthase I, is a highly conserved, ubiquitously expressed enzyme from the ribose-phosphate pyrophosphokinase family that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) from adenosine triphosphate (ATP) and ribose-5-phosphate (R5P). It is a crucial enzyme in the de novo synthesis and salvage of purines and biosynthesis of pyrimidine and pyrimidine nucleotides (1, 2). PRPS1 is activated by inorganic phosphate and magnesium and can be allosterically inhibited by ADP and purines (2, 3). Human PRPS1 is a 318 amino acid monomer that forms an active hexamer consisting of three homodimers arranged in a propellar-like shape (4). Each homodimer has an active site that binds both ATP and R5P as well as an allosteric inhibitor site. It has been well-established that many different mutations in the PRPS1 gene can lead to disease. Mutations can result in a gain of function with increased expression that leads to excess purine production present in PRS-I superactivity characterized by gout, hearing loss, hypotonia, and ataxia (2, 5). Alternatively, mutations can result in loss of function with decreased expression present in nonsyndromic sensorineural deafness (DFN-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome characterized by sensorineural hearing loss, optic atrophy, ataxia, neuropathy motor development delay and intellectual disability (2,5,6). Mis-regulation of expression and mutation of PRPS1 expression has also been shown to promote proliferation in cancers including neuroblastoma (7), squamous cell carcinoma (8), and acute lymphoblastic leukaemia (9). Additionally, PRPS1 has been shown to be regulated through its phosphorylation state to play a role in DNA repair in the innate immune response (10) and promote tumorigenesis (11).

Bioinformatics

Uniprot	P60891.2
Product By Gene ID	5631
Alternate Names	CMTX5 CMTX5ARTS deafness, X-linked 2, perceptive, congenital DFN2 DFNX1 DFNX1KIAA0967 dJ1070B1.2 (phosphoribosyl pyrophosphate synthetase 1) EC 2.7.6.1 Phosphoribosyl pyrophosphate synthase I phosphoribosyl pyrophosphate synthetase 1 PPRibP PRPS1 PRS I PRSI PRS-I ribose-phosphate diphosphokinase 1 ribose-phosphate pyrophosphokinase 1