Uridine 5'-monophosphate synthase

Function

Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5'-monophosphate (OMP), and orotidine-5'-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that decarboxylates OMP to uridine monophosphate (UMP).

Classification

Family (Pfam)

PF00215 OMPdecase, PF00156 Pribosyltran

InterPro

Aldolase_TIM, OMPdecase, OMPdecase_AS, OMPdeCOase_dom, OPRT, Or_phspho_trans_dom, PRTase-like, PRTase_dom, RibuloseP-bd_barrel

Functional cluster

Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 71

• 2EAW X-ray 2.88A
• 2JGY X-ray 1.95A
• 2P1F X-ray 1.76A
• 2QCC X-ray 1.85A
• 2QCD X-ray 2.03A
• 2QCE X-ray 1.43A
• 2QCF X-ray 1.22A
• 2QCG X-ray 1.75A
• 2QCH X-ray 1.95A
• 2QCL X-ray 1.85A
• 2QCM X-ray 1.67A
• 2QCN X-ray 1.85A
• … and 59 more

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005634 nucleus
• GO:0042802 identical protein binding
• GO:0004588 orotate phosphoribosyltransferase activity
• GO:0004590 orotidine-5'-phosphate decarboxylase activity
• GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
• GO:0044205 'de novo' UMP biosynthetic process
• GO:0019856 pyrimidine nucleobase biosynthetic process
• GO:0006225 UDP biosynthetic process
• GO:0006222 UMP biosynthetic process

Disease associations

• orotic aciduria MONDO:0009797

Drugs targeting this protein · 1

• AZARIBINE inhibitor

Related proteins · sequence + function similarity

• Uridine 5'-monophosphate synthase 0.99
• Uridine 5'-monophosphate synthase 0.97
• Uridine 5'-monophosphate synthase 0.95
• Uridine 5'-monophosphate synthase 0.77
• Uridine 5'-monophosphate synthase 0.76
• Orotidine 5'-phosphate decarboxylase 0.69
• Uridine 5'-monophosphate synthase 0.69
• Uridine 5'-monophosphate synthase 0.61
• Homocysteine S-methyltransferase 3 0.59
• Uridine 5'-monophosphate synthase 0.58
• Serine dehydratase-like 0.58
• Citramalyl-CoA lyase, mitochondrial 0.57

Literature · 14 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design. Structure · 2008
• The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
• The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am. J. Hum. Genet. · 1997
• … and 2 more in the literature graph