URH1/YDR400W Summary Help

Standard Name URH1 1
Systematic Name YDR400W
Feature Type ORF, Verified
Description Uridine nucleosidase (uridine-cytidine N-ribohydrolase); cleaves N-glycosidic bonds in nucleosides; involved in the pyrimidine salvage and nicotinamide riboside salvage pathways (1, 2, 3, 4 and see Summary Paragraph)
Name Description URidine Hydrolase 1
Chromosomal Location
ChrIV:1271063 to 1272085 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All URH1 GO evidence and references
  View Computational GO annotations for URH1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Pathways
Classical genetics
null
Large-scale survey
null
Resources
28 total interaction(s) for 25 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Two-hybrid: 1

Genetic Interactions
  • Negative Genetic: 8
  • Phenotypic Enhancement: 1
  • Positive Genetic: 8
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 340
Molecular Weight (Da) 37,960
Isoelectric Point (pI) 5.15
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:1271063 to 1272085 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 2003-09-22
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1023 1271063..1272085 2011-02-03 2003-09-22
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002808
SUMMARY PARAGRAPH for URH1

Urh1p is a uridine-cytidine N-ribohydrolase that catalyzes the cleavage of N-glycosidic bonds in uridine, cytidine, and deoxycytidine, yielding ribose and the respective base (1, 3). Urh1p is also able to cleave bonds in the prodrugs 5-fluorouridine and 5-fluorocytidine, but is not able to use inosine, adenosine, guanosine, or thymidine as substrates (3, 1). Urh1p activity is crucial for recycling pyrimidine deoxy- and ribonucleosides via the pyrimidine nucleotide salvage and deoxynucleotide salvage pathways (3).

URH1 displays similarity to genes in other organisms, including two hypothetical genes from Schizosaccharomyces pombe (SPBC1683.06c and SPAC17G8.02), an inosine/uridine-preferring nucleosidase from the protozoan parasite Crithidia fasciculata (IUNH), three ribohydrolases from E. coli (RihA, RihB, RihC), the nonspecific nucleoside hydrolase of Leishmania major, and the nonspecific nucleoside hydrolase from the parasitic organism Trypanosoma brucei (3, 1).

urh1 null mutants are viable, and can utilize uridine or cytosine, but not cytidine, as the sole source of pyrimidines (3, 1). urh1 urk1 double mutants and ura3 urk1 urh1 triple mutants are unable to utilize cytidine or uridine as the sole source of pyrimidines (3, 1). Expression of the IUNH inosine/uridine-preferring nucleosidase from C. fasciculata in a ura3 urk1 urh1 mutant is sufficient to restore growth on uridine. Growth can also be restored by expression of human uridine phosphorylase (UP), suggesting that yeast strains expressing protozoan N-ribohydrolases, or host phosphorylases, may be useful tools in drug screens for specific inhibitors (1).

About NAD biosynthesis -- de novo and salvage pathways

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for cellular redox reactions and energy metabolism. NAD also has been shown to be an important substrate in a variety of biological processes, including transcriptional regulation, DNA repair, calcium-dependent signaling pathways, calorie-restriction-mediated life-span extension and age-associated diseases (5, 6). NAD appears to affect these processes by regulating the Sir2p family of NAD-dependent deacetylases (Sirtuins) (6).

There are a number of pathways for NAD biosynthesis. In yeast and most other organisms, the two major pathways are de novo synthesis of NAD (the de novo pathway) and regeneration of NAD from its nicotinamide degradation products (the NAD salvage pathway) (7, 6). NAD is synthesized de novo from tryptophan via kynurenine (7). In this pathway tryptophan is converted to nicotinic acid mononucleotide (NaMN) in 6 enzymatic steps (catalyzed by Bna1-2p, and Bna4-7p) and one non-enzymatic step (7). At NaMN the de novo pathway converges with the NAD salvage pathway and the last two steps to NAD are shared (7, 6). In the yeast NAD salvage pathway, the vitamin precursors nicotinamide and nicotinic acid are converted to NaMN, the point of convergence with the de novo pathway (6). The steps from nicotinic acid to NAD were elucidated by Preiss and Handler and are sometimes referred to as the Preiss-Handler pathway (as reviewed in 8). Yeast can also import extracellular nicotinic acid into the cell by the permease Tna1p and then convert it to NAD via the Preiss-Handler pathway (6).

There are four additional pathways for synthesizing NAD in yeast: two salvage pathways from the vitamin precursor nicotinamide riboside (NR) and two salvage pathways from nicotinic acid riboside (NaR) (8, 4, 9). Only one of these pathways, the NR salvage pathway I, is independent of the NAD salvage pathway. In the NR salvage pathway I, NR is phosphorylated to nicotinamide mononucleotide by the kinase Nrk1p, and then adenylated to NAD by Nma1p or Nma2p (8). In the NR salvage pathway II, the hydrolase Urh1p or the phosphorylase Pnp1p split NR into a ribosyl product and nicotinamide, which subsequently is converted to NAD via the NAD salvage pathway (4). The initial steps in the NaR salvage pathways I and II are similar to those of the NR salvage pathways I and II and are catalyzed by the same enzymes, respectively. In the NaR salvage pathway I, Nrk1p phosphorylates NaR to NaMN, which subsequently is converted to NAD via the enzymes shared by the de novo and NAD salvage pathways (9). In the NaR salvage pathway II, Urh1p or Pnp1p split NR into a ribosyl product and nicotinic acid, which is first converted to NaMN and then is converted similarly to NAD (9).

Last updated: 2005-11-30 Contact SGD

References cited on this page View Complete Literature Guide for URH1
1) Mitterbauer R, et al.  (2002) Saccharomyces cerevisiae URH1 (encoding uridine-cytidine N-ribohydrolase): functional complementation by a nucleoside hydrolase from a protozoan parasite and by a mammalian uridine phosphorylase. Appl Environ Microbiol 68(3):1336-43
2) Kurtz JE, et al.  (1999) New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism. Curr Genet 36(3):130-6
3) Kurtz JE, et al.  (2002) The URH1 uridine ribohydrolase of Saccharomyces cerevisiae. Curr Genet 41(3):132-41
4) Belenky P, et al.  (2007) Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell 129(3):473-84
5) Anderson RM, et al.  (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423(6936):181-5
6) Lin SJ and Guarente L  (2003) Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol 15(2):241-6
7) Bedalov A, et al.  (2003) NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae. Mol Cell Biol 23(19):7044-54
8) Bieganowski P and Brenner C  (2004) Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell 117(4):495-502
9) Tempel W, et al.  (2007) Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD(+). PLoS Biol 5(10):e263