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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 (2, 5). NAD appears to affect these processes by regulating the Sir2p family of NAD-dependent deacetylases (Sirtuins) (5).

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) (6, 5). NAD is synthesized de novo from tryptophan via kynurenine (6). 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 (6). At NaMN the de novo pathway converges with the NAD salvage pathway and the last two steps to NAD are shared (6, 5). 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 (5). 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 7). 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 (5).

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) (7, 8, 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 (7). 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 (8). 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).", "date_edited": "2008-03-06"}, "literature_overview": {"primary_count": 39, "additional_count": 50, "review_count": 30, "go_count": 8, "phenotype_count": 6, "disease_count": 0, "interaction_count": 53, "regulation_count": 8, "ptm_count": 4, "funComplement_count": 0, "htp_count": 16, "total_count": 186}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [{"display_name": "3.5.1.19", "link": "/ecnumber/EC:3.5.1.19"}], "URS_ID": null, "main_strain": "S288C", "regulation_overview": {"regulator_count": 14, "target_count": 0}, "reference_mapping": {"563589": 1, "552344": 2, "398398": 3, "318632": 4, "490766": 5, "548869": 6, "543451": 7, "501659": 8, "495813": 9}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: PNC1", "date_created": "2000-03-16", "references": [{"id": 563589, "display_name": "Ghislain M, et al. (2002)", "citation": "Ghislain M, et al. (2002) Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1. Yeast 19(3):215-24", "pubmed_id": 11816029, "link": "/reference/S000069212", "year": 2002, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1002/yea.810"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/11816029"}]}]}, {"category": "Sequence change", "history_type": "SEQUENCE", "note": "Sequence change: A single nucleotide insertion was made in the intergenic region between ORFs PNC1/YGL037C and YGL036W.\r\n

\r\nNew    428202   ATTCACTTTTCCAGTACGTAACACCACGCGGCGCCCCTTTGTGGGGCCTGCCCCTTTTTT  428261\r\n                ||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||\r\nOld    428208   ATTCACTTTTCCAGTACGTAACACCACGCGGCGCCCCTTTGTGGG-CCTGCCCCTTTTTT  428266", "date_created": "2011-04-13", "references": [{"id": 374815, "display_name": "Engel SR, et al. (2014)", "citation": "Engel SR, et al. (2014) The reference genome sequence of Saccharomyces cerevisiae: then and now. G3 (Bethesda) 4(3):389-98", "pubmed_id": 24374639, "link": "/reference/S000156273", "year": 2014, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1534/g3.113.008995"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962479/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/24374639"}]}]}], "complexes": []},
        tabs: {"id": 1282483, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": false}
    };


	
	
	
    
    
	
    PNC1 | SGD
    
	
	
	









	
	

PNC1 / YGL037C Overview


Standard Name
PNC1 1
Systematic Name
YGL037C
SGD ID
SGD:S000003005
Feature Type
ORF , Verified
Description
Nicotinamidase that converts nicotinamide to nicotinic acid; part of the NAD(+) salvage pathway; required for life span extension by calorie restriction; lacks a peroxisomal targeting signal but is imported into peroxisomes via binding to Gpd1p; PNC1 expression responds to all known stimuli that extend replicative life span; protein increases in abundance and relative distribution to cytoplasmic foci decreases upon DNA replication stress 1 2 3 4
Name Description
Pyrazinamidase and NiCotinamidase 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Summary
Protein increases in abundance and relative distribution to cytoplasmic foci decreases upon DNA replication stress
Length (a.a.)
216
Mol. Weight (Da)
24985.5
Isoelectric Point
6.23
Median Abundance (molecules/cell)
15409 +/- 6776
Half-life (hr)
17.1

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all PNC1 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Nicotinamidase involved in nicotinate nucleotide salvage, negative regulation of ribosomal DNA (rDNA) amplification, replicative cell aging, and chromatin silencing at rDNA and telomeres; localizes to nucleus, cytoplasm, and peroxisomes

View computational annotations

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated

Pathways


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


137 total interactions for 120 unique genes

Physical Interactions

  • Affinity Capture-MS: 43
  • Affinity Capture-RNA: 7
  • Affinity Capture-Western: 1
  • Co-localization: 2
  • Co-purification: 1
  • PCA: 3
  • Proximity Label-MS: 4
  • Two-hybrid: 8

Genetic Interactions

  • Dosage Rescue: 2
  • Negative Genetic: 49
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 7
  • Positive Genetic: 7
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 1
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Regulators
14
Targets
0
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2008-03-06

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
39
Additional
50
Reviews
30

Resources


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