HEM2/YGL040C Summary Help

Standard Name HEM2 1
Systematic Name YGL040C
Alias SLU1 2 , OLE4 3 , 4
Feature Type ORF, Verified
Description Aminolevulinate dehydratase; a homo-octameric enzyme, catalyzes the conversion of 5-aminolevulinate to porphobilinogen, the second step in heme biosynthesis; enzymatic activity is zinc-dependent; localizes to the cytoplasm and nucleus (1, 3, 5, 6 and see Summary Paragraph)
Name Description HEMe biosynthesis 1, 3
Chromosomal Location
ChrVII:420555 to 419527 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All HEM2 GO evidence and references
  View Computational GO annotations for HEM2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 76 genes
Resources
Pathways
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
reduction of function
Resources
67 total interaction(s) for 62 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 6
  • PCA: 1
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 45
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 2
  • Positive Genetic: 7
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 342
Molecular Weight (Da) 37,740
Isoelectric Point (pI) 6.06
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:420555 to 419527 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1029 420555..419527 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 SGDIDS000003008
SUMMARY PARAGRAPH for HEM2

About tetrapyrrole biosynthesis

Tetrapyrroles, such as heme, siroheme, chlorophyll, and cobalamin (vitamin B12) function as cofactors in a variety of essential biological processes. Tetrapyrroles are comprised of four pyrrole rings linked together by single-carbon bridges in a linear or cyclic fashion. The cyclic tetrapyrroles heme and siroheme contain an iron-atom coordinated in their central cavity and function in respiration and sulfur assimilation, respectively. Saccharomyces cerevisiae synthesize heme and siroheme de novo via a common pathway up to the intermediate uroporphyrinogen III; oxidative decarboxylation of uroporphyrinogen III leads to the synthesis of heme while its methylation leads to siroheme synthesis.

The first committed precursor in the biosynthesis of tetrapyrroles is the five-carbon compound 5-aminolevulinic acid (ALA) (7). Animals, fungi, apicomplexan protozoa (such as the malaria parasite Plasmodium falciparum) and photosynthetic bacteria synthesize ALA from succinyl CoA and glycine (8, 9), while higher plants and other bacteria (including Escherichia coli) synthesize ALA from glutamate (8, 7)

In Saccharomyces cerevisiae, HEM1 encodes for ALA synthase, the enzyme catalyzing the first committed step in the biosynthesis of tetrapyrroles (10). Pyridoxal 5'-phosphate is an essential factor for Hem1p (10). The second step, the condensation of two molecules of ALA to form the pyrrole porphobilinogen, is catalyzed by ALA dehydratase (also known as porphobilinogen synthase; EC 4.2.1.24), a homo-octameric enzyme encoded by HEM2 (5). Hem3p and Hem4p catalyze the third and fourth steps of tetrapyrrole biosynthesis, respectively. HEM3 encodes for porphobilinogen deaminase (also known as hydroxymethylbilane synthase; EC 2.5.1.61), which catalyzes the condensation of four molecules of 4-porphobilinogen to form the linear tetrapyrrole hydroxymethylbilane (11), and HEM4 encodes for uroporphyrinogen III synthase (UROS; EC 4.2.1.75), the enzyme catalyzing the cyclization of hydroxymethylbilane and rearrangement of the fourth pyrrole to form the important intermediate uroporphyrinogen III (12). In the absence of UROS, the linear tetrapole hydroxymethylbilane undergoes non-enzymatic cyclization without rearrangement of the fourth pyrrole ring to form uroporphyrinogen I, which is not an intermediate in the synthesis of biological tetrapyrroles. Uroporphyrinogen III is a major branch point intermediate leading to biosynthesis of different tetrapyrrole-derived compounds, such as siroheme, heme, cobalamin (vitamin B12), and the methanogenic coenzyme F430 (7). S. cerevisiae is not believed to synthesize cobalamin de novo (13, 14).

Last updated: 2009-04-23 Contact SGD

References cited on this page View Complete Literature Guide for HEM2
1) Myers AM, et al.  (1987) Characterization of the yeast HEM2 gene and transcriptional regulation of COX5 and COR1 by heme. J Biol Chem 262(35):16822-9
2) Gachotte D, et al.  (1997) A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Proc Natl Acad Sci U S A 94(21):11173-8
3) Gollub EG, et al.  (1977) Yeast mutants deficient in heme biosynthesis and a heme mutant additionally blocked in cyclization of 2,3-oxidosqualene. J Biol Chem 252(9):2846-54
4) Bard M  (1972) Biochemical and genetic aspects of nystatin resistance in saccharomyces cerevisiae. J Bacteriol 111(3):649-57
5) Borralho LM, et al.  (1990) Purification of delta-aminolevulinate dehydratase from genetically engineered yeast. Yeast 6(4):319-30
6) Huh WK, et al.  (2003) Global analysis of protein localization in budding yeast. Nature 425(6959):686-91
7) Warren MJ and Scott AI  (1990) Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors. Trends Biochem Sci 15(12):486-91
8) Avissar YJ, et al.  (1989) Distribution of delta-aminolevulinic acid biosynthetic pathways among phototrophic bacterial groups. Arch Microbiol 151(6):513-9
9) Sato S, et al.  (2004) Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum. Protist 155(1):117-25
10) Volland C and Felix F  (1984) Isolation and properties of 5-aminolevulinate synthase from the yeast Saccharomyces cerevisiae. Eur J Biochem 142(3):551-7
11) Keng T, et al.  (1992) Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Mol Gen Genet 234(2):233-43
12) Amillet JM and Labbe-Bois R  (1995) Isolation of the gene HEM4 encoding uroporphyrinogen III synthase in Saccharomyces cerevisiae. Yeast 11(5):419-24
13) Hansen J, et al.  (1997) Siroheme biosynthesis in Saccharomyces cerevisiae requires the products of both the MET1 and MET8 genes. FEBS Lett 401(1):20-4
14) Raux E, et al.  (1999) The role of Saccharomyces cerevisiae Met1p and Met8p in sirohaem and cobalamin biosynthesis. Biochem J 338 ( Pt 3)():701-8