HEM4/YOR278W Summary Help

Standard Name HEM4 1
Systematic Name YOR278W
Alias SLU2 2
Feature Type ORF, Verified
Description Uroporphyrinogen III synthase; catalyzes the conversion of hydroxymethylbilane to uroporphyrinogen III, the fourth step in heme biosynthesis; deficiency in the human homolog can result in the disease congenital erythropoietic porphyria (1, 3 and see Summary Paragraph)
Name Description HEMe biosynthesis 1, 4
Chromosomal Location
ChrXV:842817 to 843644 | ORF Map | GBrowse
Gene Ontology Annotations All HEM4 GO evidence and references
  View Computational GO annotations for HEM4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Classical genetics
Large-scale survey
reduction of function
3 total interaction(s) for 3 unique genes/features.
Genetic Interactions
  • Phenotypic Enhancement: 2
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 275
Molecular Weight (Da) 30,911
Isoelectric Point (pI) 8.35
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXV:842817 to 843644 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..828 842817..843644 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005804

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) (5). Animals, fungi, apicomplexan protozoa (such as the malaria parasite Plasmodium falciparum) and photosynthetic bacteria synthesize ALA from succinyl CoA and glycine (6, 7), while higher plants and other bacteria (including Escherichia coli) synthesize ALA from glutamate (6, 5)

In Saccharomyces cerevisiae, HEM1 encodes for ALA synthase, the enzyme catalyzing the first committed step in the biosynthesis of tetrapyrroles (8). Pyridoxal 5'-phosphate is an essential factor for Hem1p (8). 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, a homo-octameric enzyme encoded by HEM2 (9). Hem3p and Hem4p catalyze the third and fourth steps of tetrapyrrole biosynthesis, respectively. HEM3 encodes for porphobilinogen deaminase (also known as hydroxymethylbilane synthase; EC, which catalyzes the condensation of four molecules of 4-porphobilinogen to form the linear tetrapyrrole hydroxymethylbilane (10), and HEM4 encodes for uroporphyrinogen III synthase (UROS; EC, the enzyme catalyzing the cyclization of hydroxymethylbilane and rearrangement of the fourth pyrrole to form the important intermediate uroporphyrinogen III (1). 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 (5). S. cerevisiae is not believed to synthesize cobalamin de novo (11, 12).

Last updated: 2009-04-23 Contact SGD

References cited on this page View Complete Literature Guide for HEM4
1) Amillet JM and Labbe-Bois R  (1995) Isolation of the gene HEM4 encoding uroporphyrinogen III synthase in Saccharomyces cerevisiae. Yeast 11(5):419-24
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) Tan FC, et al.  (2008) Identification and characterization of the Arabidopsis gene encoding the tetrapyrrole biosynthesis enzyme uroporphyrinogen III synthase. Biochem J 410(2):291-9
4) 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
5) Warren MJ and Scott AI  (1990) Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors. Trends Biochem Sci 15(12):486-91
6) Avissar YJ, et al.  (1989) Distribution of delta-aminolevulinic acid biosynthetic pathways among phototrophic bacterial groups. Arch Microbiol 151(6):513-9
7) 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
8) 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
9) Borralho LM, et al.  (1990) Purification of delta-aminolevulinate dehydratase from genetically engineered yeast. Yeast 6(4):319-30
10) Keng T, et al.  (1992) Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Mol Gen Genet 234(2):233-43
11) 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
12) 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