MET1/YKR069W Summary Help

Standard Name MET1 1, 2
Systematic Name YKR069W
Alias MET20 1 , 2 , 3
Feature Type ORF, Verified
Description S-adenosyl-L-methionine uroporphyrinogen III transmethylase; involved in the biosynthesis of siroheme, a prosthetic group used by sulfite reductase; required for sulfate assimilation and methionine biosynthesis (1, 4, 5 and see Summary Paragraph)
Name Description METhionine requiring 2
Chromosomal Location
ChrXI:571612 to 573393 | ORF Map | GBrowse
Gene Ontology Annotations All MET1 GO evidence and references
  View Computational GO annotations for MET1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
9 total interaction(s) for 9 unique genes/features.
Physical Interactions
  • Two-hybrid: 3

Genetic Interactions
  • Negative Genetic: 3
  • Positive Genetic: 2
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 593
Molecular Weight (Da) 66,125
Isoelectric Point (pI) 6.53
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:571612 to 573393 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1782 571612..573393 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 SGDIDS000001777

Met1p is an AdoMet-dependent uroporphyrinogen III transmethylase involved in the biosynthesis of siroheme (see pathway diagram), a prosthetic group employed by sulfite reductase for the 6-electron reduction of sulfite to sulfide. Siroheme is an iron-containing modified cyclic tetrapyrrole, similar in structure to heme, chlorophyll and cobalamin (vitamin B12)(1, 4). In S. cerevisiae sulfite reductase is encoded by MET10 and MET5, and plays an essential role in sulfate assimilation (see pathway diagram) and methionine biosynthesis (see pathway diagram). Although AdoMet-dependent uroporphyrinogen III transmethylases can also catalyze the first step in vitamin B12 biosynthesis S. cerevisiae does not appear to synthesize this vitamin de novo. Therefore, Met1p does not appear to function in this manner (1, 4).

Met1p, at 593 amino acids, is considerably larger than other uroporphyrinogen III transmethylases, and its N-terminal region (the first 325 aa residues) shows no apparent homology to any known protein sequence. This region is not required for any of the enzymic transformations of siroheme biosynthesis, and its function remains unknown (1, 4). A 231-aa region of Met1p, stretching from aa 326 to aa 556, shows significant homology to the Pseudomonas denitrificans CobA uroporphyrinogen III methyltransferase, and also to the C-terminal part of the CysG uroporphyrinogen III methyltransferase from Salmonella typhimurium, which can complement a met1 mutant (1, 4).

MET1 was originally identified in a screen for mutants deficient in methionine biosynthesis (2). In later studies met1 mutants were shown to lack sulfite reductase activity, causing intracellular sulfite accumulation (3, 5), consistent with Met1p's role in the biosynthesis of the sulfite reductase prosthetic group siroheme. Although initial studies showed that met1 mutants lacked 3'-phosphoadenylylsulfate (PAPS) reductase activity (3, 6), a later study contradicted this finding (5).

About siroheme biosynthesis

Sulfite and nitrite reductases catalyze the six-electron reduction of sulphite to sulfide and nitrite to ammonia, respectively, which are key enzymatic steps in the assimilation of sulfur and nitrogen into all life forms (1). Siroheme, a modified cyclic tetrapyrrole, similar in structure to heme, chlorophyll and cobalamin, is used as a prosthetic group by sulfite and nitrite reductases (7). Similar to many cyclic tetrapyrroles, siroheme coordinates with a metal in its central cavity. While siroheme and heme coordinate an iron atom, chlorophyll and cobalamin coordinate maganesium and cobalt, respectively.

Assimilatory sulfite reductases are found in bacteria, plants and fungi, but not in animals, while dissimilatory sulfite reductases are found in diverse sulfate-reducing eubacteria and some species of thermophilic archaebacteria. Assimilatory nitrite reductases are also found in bacteria, plants, and fungi, but not in the yeast Saccharomyces cerevisiae. Thus, in S. cerevisiae siroheme is used exclusively in sulfite reductase (1).

The biologically important modified tetrapyrroles, such as siroheme, heme, chlorophyll and cobalamin share a common biosynthetic pathway up to the synthesis of the first macrocyclic intermediate uroporphyrinogen-III (8). Siroheme is biosynthesized from uroporphyringoen-III in four enzymatic steps: two transmethylations, a dehydrogenation, and a ferrochelation (4). In S. cerevisiae the two transmethylations are catalyzed by Met1p, a uroporphyrin III methyltransferase that requires S-adenosyl-L-methionine (AdoMet) as a methyl donor, and the dehydrogenation and ferrochelation reactions are catalyzed by the bifunctional enzyme Met8p (4, 1, 9).

Last updated: 2007-05-31 Contact SGD

References cited on this page View Complete Literature Guide for MET1
1) 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
2) Masselot M and De Robichon-Szulmajster H  (1975) Methionine biosynthesis in Saccharomyces cerevisiae. I. Genetical analysis of auxotrophic mutants. Mol Gen Genet 139(2):121-32
3) Masselot M and Surdin-Kerjan Y  (1977) Methionine biosynthesis in Saccharomyces cerevisiae. II. Gene-enzyme relationships in the sulfate assimilation pathway. Mol Gen Genet 154(1):23-30
4) 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
5) Thomas D, et al.  (1992) Physiological analysis of mutants of Saccharomyces cerevisiae impaired in sulphate assimilation. J Gen Microbiol 138(10):2021-8
6) Thomas D, et al.  (1990) Gene-enzyme relationship in the sulfate assimilation pathway of Saccharomyces cerevisiae. Study of the 3'-phosphoadenylylsulfate reductase structural gene. J Biol Chem 265(26):15518-24
7) Murphy MJ and Siegel LM  (1973) Siroheme and sirohydrochlorin. The basis for a new type of porphyrin-related prosthetic group common to both assimilatory and dissimilatory sulfite reductases. J Biol Chem 248(19):6911-9
8) Warren MJ and Scott AI  (1990) Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors. Trends Biochem Sci 15(12):486-91
9) Schubert HL, et al.  (2002) The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase. EMBO J 21(9):2068-75