PMT6/YGR199W Summary Help

Standard Name PMT6
Systematic Name YGR199W
Feature Type ORF, Verified
Description Protein O-mannosyltransferase; transfers mannose from dolichyl phosphate-D-mannose to protein serine/threonine residues of secretory proteins; reaction is essential for cell wall rigidity; member of a family of mannosyltransferases (1 and see Summary Paragraph)
Name Description Protein O-MannosylTransferase
Chromosomal Location
ChrVII:897502 to 899781 | ORF Map | GBrowse
Gene Ontology Annotations All PMT6 GO evidence and references
  View Computational GO annotations for PMT6
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Regulators 4 genes
Large-scale survey
70 total interaction(s) for 48 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Biochemical Activity: 1
  • PCA: 2

Genetic Interactions
  • Negative Genetic: 52
  • Phenotypic Enhancement: 1
  • Positive Genetic: 13

Expression Summary
Length (a.a.) 759
Molecular Weight (Da) 88,025
Isoelectric Point (pI) 6.83
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVII:897502 to 899781 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2280 897502..899781 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 SGDIDS000003431

Protein O-mannosylation is an evolutionarily conserved, essential posttranslational modification that impacts a variety of cellular processes in both fungi and mammals (2). It is initiated at the endoplasmic reticulum by a family of dolichyl phosphate mannose-dependent protein O-mannosyltransferases (PMTs) which is conserved from yeast to humans (3). PMTs transfer mannose residues from dolichyl phosphate-D-mannose to protein seryl/threonyl residues. In fungi, secretory proteins are commonly mannosylated by protein O-mannosyltransferase (PMT) in the ER, and subsequently glycosylated by several glycosyltransferases in the Golgi apparatus to form glycoproteins with diverse O-glycan structures (4). The evolutionarily conserved PMT family is classified into three subfamilies - PMT1, PMT2, and PMT4 - which mannosylate distinct target proteins (5, 6, 2). Members of the PMT1 subfamily (Pmt1p and Pmt5p) interact with members of the PMT2 subfamily (Pmt2p and Pmt3p), with Pmt1p-Pmt2p and Pmt5p-Pmt3p heterodimers representing the predominant forms (7, 3). Under certain conditions, Pmt1p can also interact with Pmt3p, and Pmt5p with Pmt2p. PMT2 and PMT3 are paralogs that arose from the whole genome duplication (8). Unlike the PMT1 and PMT2 subfamily members, the single member of the PMT4 subfamily (Pmt4p) acts as a homodimeric complex (6, 2). The Pmt1p-Pmt2p complex also functions in connection with the ERAD machinery and participates in ER protein quality control (9, 10, 11).

PMTs are integral membrane proteins with two hydrophilic loops (loops 1 and 5) facing the ER lumen. Formation of dimeric PMT complexes is crucial for mannosyltransferase activity. Loop 1 contains an Asp-Glu motif that is highly conserved among PMTs. Single amino acid substitutions in this motif completely abolish activity of Pmt4p complexes, while both acidic residues need to be changed to eliminate activity of Pmt1p-Pmt2p complexes (12). Arg64, Glu78, Arg138 and Leu408 of Pmt1p are important for transferase activity, while Arg138 is also essential for complex formation with Pmt2p (13, 3).

In fungi the PMT family is highly redundant, and only the simultaneous deletion of PMT1/PMT2 and PMT4 subfamily members is lethal (14, 6). pmt1 deletion mutants are highly sensitive to zymolyase (15). Strains bearing a pmt1 pmt2 double disruption show a severe growth defect (16). In cells lacking PMT4, Fus1p is not glycosylated and accumulates in late Golgi structures (17). Mutants lacking both functional Pmt2p and Pmt4p lyse as small-budded cells in the absence of osmotic stabilization, and treatment with mating pheromone causes pheromone-induced cell death (18). These phenotypes are partially suppressed by overexpression of upstream elements of the protein kinase C cell integrity pathway (18). Induction of Mpk1p/Slt2p tyrosine phosphorylation does not occur in pmt2 pmt4 double mutants during exposure to mating pheromone or elevated temperature (18). Further, Slg1p, Wsc2p, and Mid2p are aberrantly processed in pmt mutants (18). Adhesin subunit Aga1p and the alpha-agglutinin Ag(alpha)1p are hypoglycosylated in cells lacking PMT1 and PMT2, with phenotypes manifested only in MATalpha cells for single mutants and in both cell types when both genes are absent (19). In Schizosaccharomyces pombe, lack of protein O-mannosyltransferase activity results in abnormal cell wall and septum formation, severely affecting cell morphology and cell-cell separation (20). PMTs are crucial for viability in mouse (20). In humans, O-mannosylation defects are associated with Walker-Warburg syndrome, a type of severe recessive congenital muscular dystrophy associated with defects in neuronal migration that produce complex brain and eye abnormalities (2, 3).

PMTs have also been identified in Ustilago maydis (21), Cryptococcus neoformans, Candida albicans (22), Aspergillus nidulans (23), Kluyveromyces lactis (14), and Trichoderma reesei (24), as well as Corynebacterium glutamicum (25). Because O-mannosylation of specific secretory proteins in C. albicans affects several virulence traits such as morphogenesis, adhesive properties, and antifungal resistance, PMTs can be considered as potential antifungal targets against human fungal pathogens (26, 27, 28). Similarly, O-mannosylation of specific secretory proteins of the bacterial pathogen Mycobacterium tuberculosis contributes significantly to virulence (28). PMTs are absent in green plants, and are therefore potential targets for antifungal drugs against phytopathogenic fungi (6).

Last updated: 2012-09-11 Contact SGD

References cited on this page View Complete Literature Guide for PMT6
1) Gentzsch M and Tanner W  (1996) The PMT gene family: protein O-glycosylation in Saccharomyces cerevisiae is vital. EMBO J 15(21):5752-9
2) Hutzler J, et al.  (2007) Membrane association is a determinant for substrate recognition by PMT4 protein O-mannosyltransferases. Proc Natl Acad Sci U S A 104(19):7827-32
3) Akasaka-Manya K, et al.  (2011) Different roles of the two components of human protein O-mannosyltransferase, POMT1 and POMT2. Biochem Biophys Res Commun 411(4):721-5
4) Goto M  (2007) Protein o-glycosylation in fungi: diverse structures and multiple functions. Biosci Biotechnol Biochem 71(6):1415-27
5) Gentzsch M and Tanner W  (1997) Protein-O-glycosylation in yeast: protein-specific mannosyltransferases. Glycobiology 7(4):481-6
6) Girrbach V and Strahl S  (2003) Members of the evolutionarily conserved PMT family of protein O-mannosyltransferases form distinct protein complexes among themselves. J Biol Chem 278(14):12554-62
7) Gentzsch M, et al.  (1995) Protein O-glycosylation in Saccharomyces cerevisiae: the protein O-mannosyltransferases Pmt1p and Pmt2p function as heterodimer. FEBS Lett 377(2):128-30
8) 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
9) Nakatsukasa K, et al.  (2004) Roles of O-mannosylation of aberrant proteins in reduction of the load for endoplasmic reticulum chaperones in yeast. J Biol Chem 279(48):49762-72
10) Hirayama H, et al.  (2008) O-Mannosylation is Required for Degradation of the Endoplasmic Reticulum-associated Degradation Substrate Gas1*p via the Ubiquitin/Proteasome Pathway in Saccharomyces cerevisiae. J Biochem 143(4):555-67
11) Goder V and Melero A  (2011) Protein O-mannosyltransferases participate in ER protein quality control. J Cell Sci 124(Pt 1):144-53
12) Lommel M, et al.  (2011) A conserved acidic motif is crucial for enzymatic activity of protein O-mannosyltransferases. J Biol Chem 286(46):39768-75
13) Girrbach V, et al.  (2000) Structure-function analysis of the dolichyl phosphate-mannose: protein O-mannosyltransferase ScPmt1p. J Biol Chem 275(25):19288-96
14) Immervoll T, et al.  (1995) PMT3 and PMT4, two new members of the protein-O-mannosyltransferase gene family of Saccharomyces cerevisiae. Yeast 11(14):1345-51
15) Bourdineaud JP, et al.  (1998) Pmt1 mannosyl transferase is involved in cell wall incorporation of several proteins in Saccharomyces cerevisiae. Mol Microbiol 27(1):85-98
16) Lussier M, et al.  (1995) Protein O-glycosylation in yeast. The PMT2 gene specifies a second protein O-mannosyltransferase that functions in addition to the PMT1-encoded activity. J Biol Chem 270(6):2770-5
17) Proszynski TJ, et al.  (2004) O-glycosylation as a sorting determinant for cell surface delivery in yeast. Mol Biol Cell 15(4):1533-43
18) Lommel M, et al.  (2004) Aberrant processing of the WSC family and Mid2p cell surface sensors results in cell death of Saccharomyces cerevisiae O-mannosylation mutants. Mol Cell Biol 24(1):46-57
19) Huang G, et al.  (2003) Posttranslational modifications required for cell surface localization and function of the fungal adhesin Aga1p. Eukaryot Cell 2(5):1099-114
20) Willer T, et al.  (2005) Protein O-mannosylation is crucial for cell wall integrity, septation and viability in fission yeast. Mol Microbiol 57(1):156-70
21) Fernandez-Alvarez A, et al.  (2009) The O-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration in Ustilago maydis. Plant Cell 21(10):3397-412
22) Willger SD, et al.  (2009) Characterization of the PMT gene family in Cryptococcus neoformans. PLoS One 4(7):e6321
23) Shaw BD and Momany M  (2002) Aspergillus nidulans polarity mutant swoA is complemented by protein O-mannosyltransferase pmtA. Fungal Genet Biol 37(3):263-70
24) Zakrzewska A, et al.  (2003) cDNA encoding protein O-mannosyltransferase from the filamentous fungus Trichoderma reesei; functional equivalence to Saccharomyces cerevisiae PMT2. Curr Genet 43(1):11-6
25) Mahne M, et al.  (2006) The Corynebacterium glutamicum gene pmt encoding a glycosyltransferase related to eukaryotic protein-O-mannosyltransferases is essential for glycosylation of the resuscitation promoting factor (Rpf2) and other secreted proteins. FEMS Microbiol Lett 259(2):226-33
26) Timpel C, et al.  (2000) Morphogenesis, adhesive properties, and antifungal resistance depend on the Pmt6 protein mannosyltransferase in the fungal pathogen candida albicans. J Bacteriol 182(11):3063-71
27) Ernst JF and Prill SK  (2001) O-glycosylation. Med Mycol 39 Suppl 1():67-74
28) Lengeler KB, et al.  (2008) Protein-O-mannosyltransferases in virulence and development. Cell Mol Life Sci 65(4):528-44