Table 3.
Yeast genes that modify α-syn toxicity when overexpressed.
| Yeast Gene | Type | Strength | Human ortholog(s) | Proposed function |
|---|---|---|---|---|
| Amino Acid Transport | ||||
| AVT4 | suppressor | 3 | SLC36A1 | Vacuolar transporter; exports large neutral amino acids from the vacuole |
| SLC36A2 | ||||
| SLC36A3 | ||||
| SLC36A4 | ||||
| DIP5 | suppressor | 3 | SLC7A1 | Dicarboxylic amino acid permease |
| SLC7A14 | ||||
| SLC7A2 | ||||
| SLC7A3 | ||||
| SLC7A4 | ||||
| SLC7A13 | ||||
| LST8 | suppressor | 3 | GBL | Component of the TOR signaling pathway |
| Autophagy | ||||
| NVJ1 | suppressor | 2 | Nuclear envelope protein; functions during piecemeal microautophagy of the nucleus (PMN) | |
| Cytoskeleton | ||||
| ICY1 | suppressor | 4 | Protein that interacts with the cytoskeleton | |
| ICY2 | suppressor | 4 | Protein that interacts with the cytoskeleton | |
| Manganese transport | ||||
| CCC1 | suppressor | 4 | Putative vacuolar Fe2+/Mn2+ transporter | |
| PMR1 | enhancer | −7 | ATP2C1 | High affinity Ca2+/Mn2+ P-type ATPase required for Ca2+ and Mn2+ transport into Golgi |
| ATP2C2 | ||||
| Protein phosphorylation | ||||
| IME2 | suppressor | 4 | ICK | Serine/threonine protein kinase involved in activation of meiosis |
| PTP2 | suppressor | 3 | PTPRE, PTPRC, PTPN22, PTPRG | Phosphotyrosine-specific protein phosphatase involved in osmolarity sensing |
| GIP2 | suppressor | 3 | PPP1R3A | Putative regulatory subunit of the protein phosphatase Glc7p, involved in glycogen metabolism |
| PPP1R3B | ||||
| PPP1R3C | ||||
| PPP1R3D | ||||
| PPP1R3E | ||||
| YCK3 | suppressor | 3 | CSNK1G1 | Palmitoylated, vacuolar membranelocalized casein kinase I isoform |
| CSNK1G2 | ||||
| CSNK1G3 | ||||
| RCK1 | suppressor | 3 | CAMK1G | Protein kinase involved in the response to oxidative stress |
| CDC5 | suppressor (Cdc5 overexpression is toxic; in presence of a-syn it rescues/rescued) | 3 | PLK2 | Polo-like kinase; found at bud neck, nucleus and SPBs; has multiple functions in mitosis and cytokinesis |
| PTC4 | suppressor | 1 | PPM1G | Cytoplasmic type 2C protein phosphatase |
| SIT4 | enhancer | −2 | PPP6C | Type 2A-related serine-threonine phosphatase. |
| CAX4 | enhancer | −3 | DOLPP1 | Dolichyl pyrophosphate phosphatase, required for Dol-P-P-linked oligosaccharide intermediate synthesis and protein N-glycosylation. |
| PPZ2 | enhancer | −3 | PPP1CC | Serine/threonine protein phosphatase Z |
| PPP1CB | ||||
| PPP1CA | ||||
| PPZ1 | enhancer | −8 | PPP1CA | Serine/threonine protein phosphatase Z |
| PPP1CB | ||||
| PPP1CC | ||||
| Transcription/Translation | ||||
| CUP9 | suppressor | 3 | MEIS1 | Transcriptional repressor involved in copper ion homeostasis |
| MEIS2 | ||||
| MEIS3 | ||||
| NR_002211 | ||||
| .1 PKNOX1 | ||||
| PKNOX2 | ||||
| Q99687-3 | ||||
| TGIF1 | ||||
| TGIF2 | ||||
| TGIF2LX | ||||
| HAP4 | suppressor | 4 | Transcriptional activator and global regulator of respiratory gene expression | |
| FZF1 | suppressor | 3 | KLF15 | Key transcriptional regulator of cellular response to nitrosative stress |
| KLF11 | ||||
| ZNF624 | ||||
| MGA2 | suppressor | 3 | ANKRD1 | ER membrane protein involved in regulation of OLE1 transcription |
| OSBPL1A | ||||
| MKS1 | enhancer | −5 | Pleiotropic negative transcriptional regulator involved in Ras-CAMP and lysine biosynthetic pathways and nitrogen regulation; involved in retrograde (RTG) mitochondria-to-nucleus signaling | |
| VHR1 | suppressor | 3 | Transcriptional activator | |
| JSN1 | suppressor | 2 | PUM1 | Member of the Puf family of RNAbinding proteins, interacts with mRNAs encoding membrane-associated proteins |
| SUT2 | enhancer | −3 | Putative transcription factor; multicopy suppressor of mutations that cause low activity of the cAMP/protein kinase A pathway | |
| TIF4632 | suppressor | 3 | EIF4G1 | Translation initiation factor eIF4G, subunit of the mRNA cap-binding protein complex (eIF4F) |
| EIF4G2 | ||||
| EIF4G3 | ||||
| STB3 | suppressor | 3 | Protein that binds Sin3p in a two-hybrid assay. | |
| MATALPHA1 | enhancer | −5 | Transcriptional co-activator involved in regulation of mating-type-specific gene expression | |
| Trehalose biosynthesis | ||||
| UGP1 | suppressor | 4 | UGP2 | UDP-glucose pyrophosphorylase, catalyses the formation of UDP-Glc, a precursor to trehalose |
| TPS3 | suppressor | 3 | Regulatory subunit of trehalose-6-phosphate synthase/phosphatase complex, which synthesizes trehalose | |
| NTH1 | suppressor | 2 | TREH | Neutral trehalase, degrades trehalose; required for thermotolerance and may mediate resistance to other cellular stresses |
| Ubiquitin-related | ||||
| CDC4 | suppressor | 4 | FBXW7 | F-box, associates with Skp1p and Cdc53p to form a complex, SCFCdc4, which acts as ubiquitin-protein ligase |
| UIP5 | suppressor | 4 | Protein of unknown function that interacts with Ulp1p, a Ubl (ubiquitin-like protein)-specific protease | |
| HRD1 | suppressor | 4 | AMFR | Ubiquitin-protein ligase required for endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins |
| SYVNI | ||||
| UBP11 | enhancer | −3 | USP21 | Ubiquitin-specific protease that cleaves ubiquitin from ubiquitinated proteins. |
| UBP7 | enhancer | −4 | USP21 | Ubiquitin-specific protease that cleaves ubiquitin-protein fusions. |
| Vesicular transport, ER-Golgi | ||||
| YPT1 | suppressor | 5 | RAB10 | Ras-like small GTPase, involved in the ER-to-Golgi step of the secretory pathway |
| RAB13 | ||||
| RAB1A | ||||
| RAB1C | ||||
| RAB8A | ||||
| RAB8B | ||||
| YKT6 | suppressor | 4 | YKT6 | v-SNARE involved in trafficking to and within the Golgi, endocytic trafficking to the vacuole, and vacuolar fusion |
| BRE5 | suppressor | 4 | G3BP2 | Ubiquitin protease cofactor, forms deubiquitination complex with Ubp3p to regulate ER-Golgi transport |
| SEC21 | suppressor | 4 | COPG2 | Gamma subunit of coatomer, a heptameric protein complex that together with Arf1p forms the COPI coat |
| COPG | ||||
| UBP3 | suppressor | 3 | USP10 | Ubiquitin-specific protease that interacts with Bre5p to co-regulate anterograde and retrograde transport between ER and Golgi |
| ERV29 | suppressor | 3 | SURF4 | Protein localized to COPII-coated vesicles, involved in vesicle formation and incorporation of specific secretory cargo. |
| SEC28 | suppressor | 3 | COPE | Epsilon-COP subunit of the coatomer; regulates retrograde Golgi-to-ER protein traffic; stabilizes Cop1p |
| SFT1 | suppressor | 2 | mouse BET1 | Intra-Golgi v-SNARE, required for transport of proteins between an early and a later Golgi compartment. |
| GLO3 | enhancer | −1 | ARFGAP3 | ADP-ribosylation factor GTPase activating protein (ARF GAP), involved in ER-Golgi transport |
| ZNF289 | ||||
| TRS120 | enhancer | −2 | NIBP | One of 10 subunits of the transport protein particle (TRAPP) complex of the cis-Golgi which mediates vesicle docking and fusion |
| GYP8 | enhancer | −2 | TBC1D20 | GTPase-activating protein for yeast Rab family members; Ypt1p is the preferred in vitro substrate |
| YIP3 | enhancer | −2 | RABAC1 | Protein localized to COPII vesicles, proposed to be involved in ER to Golgi transport; interacts with Rab GTPases |
| BET4 | enhancer | −3 | RABGGTA | Alpha subunit of Type II geranylgeranyltransferase; provides a membrane attachment moiety to Rab-like proteins Ypt1p and Sec4p |
| SLY41 | enhancer | −5 | SLC35E1 | Protein involved in ER-to-Golgi transport. |
| GOS1 | enhancer | −2 | GOSR1 | v-SNARE protein involved in Golgi transport, homolog of the mammalian protein GOS-28/GS28 |
| SEC31 | enhancer | −2 | SEC31A | Essential phosphoprotein component (p150) of the COPII coat of secretory pathway vesicles, in complex with Sec13p; required for ER-derived transport vesicle formation |
| SEC31B | ||||
| Other cellular processes | ||||
| PFS1 | suppressor | 4 | Sporulation protein required for prospore membrane formation at selected spindle poles | |
| PDE2 | suppressor | 4 | PDE10A | High-affinity cyclic AMP phosphodiesterase, component of the cAMP-dependent protein kinase signaling system |
| PDE11A | ||||
| PDE1A | ||||
| PDE1B | ||||
| PDE1C | ||||
| PDE2A | ||||
| PDE3A | ||||
| PDE3B | ||||
| PDE4A | ||||
| PDE4B | ||||
| PDE4C | ||||
| PDE4D | ||||
| PDE5A | ||||
| PDE6A | ||||
| PDE6B | ||||
| PDE6C | ||||
| PDE7A | ||||
| PDE7B | ||||
| PDE8A | ||||
| PDE8B | ||||
| PDE9A | ||||
| MUM2 | suppressor | 4 | Interacts with Orc2p, which is a component of the origin recognition complex. | |
| OSH3 | suppressor | 3 | OSBPL1A | Member of an oxysterol-binding protein family, functions in sterol metabolism |
| OSBPL2 | ||||
| OSBPL3 | ||||
| OSBPL6 | ||||
| OSBPL7 | ||||
| PHO80 | suppressor | 3 | Cyclin, negatively regulates phosphate metabolism | |
| OSH2 | suppressor | 3 | OSBPL3 | Member of an oxysterol-binding protein family, functions in sterol metabolism |
| OSBP | ||||
| OSBP2 | ||||
| ISN1 | suppressor | 2 | Inosine 5′-monophosphate (IMP)-specific 5′-nucleotidase | |
| EPS1 | enhancer | −1 | Protein disulfide isomerase-related protein involved in endoplasmic reticulum retention of resident ER proteins. | |
| IDS2 | enhancer | −2 | Protein involved in modulation of Ime2p activity during meiosis | |
| QDR3 | suppressor | 4 | Multidrug transporter of the major facilitator superfamily, required for resistance to quinidine, barban, cisplatin, and bleomycin | |
| TPO4 | enhancer | −3 | Polyamine transport protein, recognizes spermine, putrescine, and spermidine; localizes to the plasma membrane; member of the major facilitator superfamily | |
| IZH3 | enhancer | −2 | Membrane protein involved in zinc metabolism, member of the four-protein IZH family, expression induced by zinc deficiency; deletion reduces sensitivity to elevated zinc and shortens lag phase, overexpression reduces Zap1p activity | |
| Unknown Function | ||||
| YKL063C | suppressor | 4 | Uncharacterized, GFP-fusion localizes to the Golgi | |
| YML081W | suppressor | 4 | EGR3 | Uncharacterized, GFP-fusion localizes to the nucleus |
| YNR014W | suppressor | 4 | Uncharacterized, expression is cell-cycle regulated and heat-inducible | |
| YKL088W | suppressor | 4 | PPCDC | Protein required for cell viability. Predicted phosphopantothenoylcysteine decarboxylase |
| YML083C | suppressor | 3 | Uncharacterized, strong increase in transcript abundance during anaerobic growth compared to aerobic growth | |
| YDR374C | suppressor | 3 | YTHDF1 | Uncharacterized |
| YTHDF2 | ||||
| YTHDF3 | ||||
| YOR291W (YPK9) | suppressor | 3 | ATP13A2 | Probable cation-transporting ATPase 2 |
| (PARK9) | ||||
| ATP13A3 | ||||
| ATP13A4 | ||||
| ATP13A5 | ||||
| YDL121C | suppressor | 2 | Uncharacterized, GFP-fusion localizes to the ER | |
| YBR030W | suppressor | 2 | Uncharacterized, predicted to function in phospholipid metabolism | |
| YMR111C | suppressor | 2 | Uncharacterized, GFP-fusion localizes to the nucleus | |
| YOR129C | suppressor | 2 | Putative component of the outer plaque of the spindle pole body; may be involved in cation homeostasis or multidrug resistance. | |