CDC19/YAL038W Summary Help

Standard Name CDC19 1
Systematic Name YAL038W
Alias PYK1 2
Feature Type ORF, Verified
Description Pyruvate kinase; functions as a homotetramer in glycolysis to convert phosphoenolpyruvate to pyruvate, the input for aerobic (TCA cycle) or anaerobic (glucose fermentation) respiration; regulated via allosteric activation by fructose bisphosphate; CDC19 has a paralog, PYK2, that arose from the whole genome duplication (3, 4, 5 and see Summary Paragraph)
Name Description Cell Division Cycle 6
Chromosomal Location
ChrI:71786 to 73288 | ORF Map | GBrowse
Gbrowse
Genetic position: -45 cM
Gene Ontology Annotations All CDC19 GO evidence and references
  View Computational GO annotations for CDC19
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 19 genes
Resources
Pathways
Classical genetics
conditional
Large-scale survey
null
overexpression
reduction of function
repressible
Resources
162 total interaction(s) for 143 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 101
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 1
  • Biochemical Activity: 9
  • Co-localization: 2
  • Co-purification: 1
  • PCA: 2
  • Protein-RNA: 6
  • Reconstituted Complex: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Dosage Rescue: 1
  • Negative Genetic: 19
  • Phenotypic Enhancement: 1
  • Positive Genetic: 1
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 5

Resources
Expression Summary
histogram
Resources
Length (a.a.) 500
Molecular Weight (Da) 54,544
Isoelectric Point (pI) 7.66
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrI:71786 to 73288 | ORF Map | GBrowse
SGD ORF map
Genetic position: -45 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1503 71786..73288 2011-02-03 1996-07-31
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 SGDIDS000000036
SUMMARY PARAGRAPH for CDC19

Glycolysis is the lysis, or splitting, of one molecule of glucose into two molecules of pyruvate, producing a net gain of two ATP molecules. Pyruvate can then be used in anaerobic (fermentation) or aerobic (respiration) metabolism. The glycolysis pathway and the genes involved are illustrated here.

CDC19 encodes pyruvate kinase (7) which catalyzes the conversion of phosphoenolpyruvate to pyruvate, the final step in glycolysis (8). cdc19 deletion mutants cannot grow using glucose or other fermentable sugars as the sole carbon source, but grow normally on ethanol or lactate indicating that there is an alternate route for pyruvate synthesis (2,9,10). Genetic studies indicated that MAE1 is the likely candidate for this role. MAE1 encodes malic enzyme which catalyzes the oxidative decarboxylation of malate to pyruvate (10). Indeed, a cdc19 mae1 double deletion mutant cannot grow using ethanol as the sole carbon source (10). Genetic analysis of CDC19 also showed that it is involved in the cell division cycle; temperature-sensitive cdc19 mutants arrest growth in G1 at the restrictive temperature of 36 degrees C (11).

Overexpression of PYK2, which encodes a second yeast pyruvate kinase, restores growth on glucose to cdc19 mutant cells (12). However, CDC19 is tightly regulated and activated by fructose-1,6-bisphosphate (FBP) whereas PYK2 is subject to glucose repression and appears to be insensitive to FBP levels, suggesting that it may be active when FBP levels are too low to activate CDC19 (12). Therefore, PYK1 appears to be the main pyruvate kinase in the glycolytic pathway (12, 2, 13).

Transcription of CDC19 is induced in the presence of glucose (14, 15); the CDC19 promoter contains binding sites for the transcription factors Rap1p and Abf1p (16). Genes encoding pyruvate kinase have been identified in several other species, including human (PKLR/PK1) (OMIM) and mouse (17); mutations in the human gene can cause hemolytic anemia (OMIM) (18).

Last updated: 2005-07-27 Contact SGD

References cited on this page View Complete Literature Guide for CDC19
1) Link, A. and Olson, M.  (1989) Personal Communication, Mortimer Map Edition 10
2) Sprague GF Jr  (1977) Isolation and characterization of a Saccharomyces cerevisiae mutant deficient in pyruvate kinase activity. J Bacteriol 130(1):232-41
3) Pearce AK, et al.  (2001) Pyruvate kinase (Pyk1) levels influence both the rate and direction of carbon flux in yeast under fermentative conditions. Microbiology 147(Pt 2):391-401
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Xu YF, et al.  (2012) Regulation of yeast pyruvate kinase by ultrasensitive allostery independent of phosphorylation. Mol Cell 48(1):52-62
6) Hartwell LH, et al.  (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352-9
7) Burke RL, et al.  (1983) The isolation, characterization, and sequence of the pyruvate kinase gene of Saccharomyces cerevisiae. J Biol Chem 258(4):2193-201
8) Stryer L  (1988) Biochemistry (3rd ed.). New York: W. H. Freeman and Company
9) Maitra PK and Lobo Z  (1977) Pyruvate kinase mutants of Saccharomyces cerevisiae: biochemical and genetic characterisation. Mol Gen Genet 152(3):193-200
10) Boles E, et al.  (1998) Identification and characterization of MAE1, the Saccharomyces cerevisiae structural gene encoding mitochondrial malic enzyme. J Bacteriol 180(11):2875-82
11) Hartwell LH, et al.  (1973) Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants. Genetics 74(2):267-286
12) Boles E, et al.  (1997) Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate. J Bacteriol 179(9):2987-93
13) Fraenkel DG  (2003) The top genes: on the distance from transcript to function in yeast glycolysis. Curr Opin Microbiol 6(2):198-201
14) Moore PA, et al.  (1991) Yeast glycolytic mRNAs are differentially regulated. Mol Cell Biol 11(10):5330-7
15) Johnston M and Carlson M  (1992) "Regulation of carbon and phosphate utilization." Pp. 193-281 in The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression, edited by Jones EW, Pringle JR and Broach JR. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
16) Chambers A, et al.  (1990) ARS binding factor 1 binds adjacent to RAP1 at the UASs of the yeast glycolytic genes PGK and PYK1. Nucleic Acids Res 18(18):5393-9
17) Kanno H, et al.  (1995) Primary structure of murine red blood cell-type pyruvate kinase (PK) and molecular characterization of PK deficiency identified in the CBA strain. Blood 86(8):3205-10
18) Foury F  (1997) Human genetic diseases: a cross-talk between man and yeast. Gene 195(1):1-10