Csg2 is a ten-transmembrane protein of the endoplasmic reticulum membrane in Saccharomyces cerevisiae with two linked roles. It is the shared regulatory subunit of the two inositol phosphorylceramide (IPC) mannosyltransferase complexes, Sur1(Csg1)-Csg2 and Csh1-Csg2, which convert IPC and GDP-mannose into mannosylinositol phosphorylceramide (MIPC); Csg2 is not itself the glycosyltransferase but is required for full Sur1 activity and for any Csh1 activity. Without Csg2, IPC accumulates and cells become sensitive to high extracellular Ca2+. Csg2 also acts as an ER calcium release channel that limits luminal ER Ca2+; under nitrogen starvation its loss raises ER Ca2+, perturbs sphingolipid synthesis (phytosphingosine accumulation) and blocks autophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000324 fungal-type vacuole | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: HDA from the SWAT-GFP library placing Csg2 at the vacuole. Targeted immunofluorescence and the 2023 study localise Csg2 to the ER membrane; vacuolar signal may reflect turnover of tagged protein. Reason: Single high-throughput observation inconsistent with targeted ER localisation. Supporting Evidence: PMID:37349354 Csg2 is localized at the ER membranes and functions as a calcium release channel maintaining the calcium homeostasis in ER. |
| GO:0005515 protein binding | IPI PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | REMOVE | Summary: IPI (Uemura et al. 2003) with Sur1/Csg1 (P33300), the catalytic MIPC synthase subunit. The interaction defines the Sur1-Csg2 mannosyltransferase complex, already captured by GO:0031501. Reason: Uninformative 'protein binding' (the interaction is real); represented by mannosyltransferase complex membership and enzyme regulator activity. Supporting Evidence: PMID:12954640 We also revealed that Csg2p interacts with both Csg1p and Csh1p. |
| GO:0005515 protein binding | IPI PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | REMOVE | Summary: IPI (Uemura et al. 2003) with Csh1 (P38287), the second MIPC synthase catalytic subunit. Captured by complex membership. Reason: Uninformative 'protein binding'; represented by GO:0031501 and GO:0030234. Supporting Evidence: PMID:12954640 We also revealed that Csg2p interacts with both Csg1p and Csh1p. |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | REMOVE | Summary: IPI from a large-scale split-ubiquitin membrane interactome (Miller et al. 2005) with Csh1. Corroborates the Csh1-Csg2 complex. Reason: Uninformative 'protein binding'; complex captured by GO:0031501. Supporting Evidence: PMID:12954640 two distinct inositol phosphorylceramide mannosyltransferase complexes, Csg1p-Csg2p and Csh1p-Csg2p, exist |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | REMOVE | Summary: IPI from the split-ubiquitin screen with Shr3 (Q02774), an ER membrane chaperone for amino acid permeases that interacts with many polytopic ER proteins. No functional link to Csg2 activity. Reason: Uninformative 'protein binding' from a high-throughput screen; no functional consequence shown. Supporting Evidence: PMID:16093310 Large-scale identification of yeast integral membrane protein interactions. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: IPI from the in vivo PCA interactome (Tarassov et al. 2008) with Shr3. High-throughput, no functional information. Reason: Uninformative 'protein binding'; no functional consequence shown. Supporting Evidence: PMID:18467557 An in vivo map of the yeast protein interactome. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI from a proteome-wide interactome (Michaelis et al. 2023) with Sur1, recovering the MIPC synthase complex. Reason: Uninformative 'protein binding'; captured by GO:0031501. Supporting Evidence: PMID:12954640 We also revealed that Csg2p interacts with both Csg1p and Csh1p. |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HDA from the SWAT-GFP library placing Csg2 in the ER, consistent with targeted studies. Supporting Evidence: PMID:7854312 Immunofluorescent staining of the yeast cells expressing epitope-tagged Cls2p suggests that Cls2p is localized to endoplasmatic reticulum (ER) membrane. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:37349354 The ER calcium channel Csg2 integrates sphingolipid metaboli... | ACCEPT | Summary: IDA (Liu et al. 2023) - Csg2 localises to ER membranes, where it acts as a Ca2+ release channel. Supporting Evidence: PMID:37349354 Csg2 is localized at the ER membranes and functions as a calcium release channel maintaining the calcium homeostasis in ER. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:7854312 The CLS2 gene encodes a protein with multiple membrane-spann... | ACCEPT | Summary: IDA (Takita et al. 1995) - immunofluorescence of epitope-tagged Cls2/Csg2 shows ER membrane localisation. Supporting Evidence: PMID:7854312 Immunofluorescent staining of the yeast cells expressing epitope-tagged Cls2p suggests that Cls2p is localized to endoplasmatic reticulum (ER) membrane. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR031581 Csg2 family; UniProt SL-0097). Correct. Supporting Evidence: file:yeast/CSG2/CSG2-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005794 Golgi apparatus | IDA PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | KEEP AS NON CORE | Summary: IDA from Uemura et al. 2003 (abstract-only cached) for Golgi apparatus. MIPC synthesis is generally thought to occur in the Golgi and the curator saw the full text; Csg2 steady-state localisation in other studies is the ER, so a Golgi pool is plausible but secondary. Reason: Curator-reviewed experimental localisation (deferred to); not the main documented site of Csg2. Supporting Evidence: PMID:12954640 two distinct inositol phosphorylceramide mannosyltransferase complexes, Csg1p-Csg2p and Csh1p-Csg2p, exist |
| GO:0005794 Golgi apparatus | NAS PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | KEEP AS NON CORE | Summary: NAS from the same paper for Golgi apparatus, presumably from the authors' statement about the site of MIPC synthesis. Reason: Author statement duplicating the IDA row; secondary to ER localisation. Supporting Evidence: PMID:12954640 two distinct inositol phosphorylceramide mannosyltransferase complexes, Csg1p-Csg2p and Csh1p-Csg2p, exist |
| GO:0006676 mannosyl diphosphorylinositol ceramide metabolic process | IDA PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | MODIFY | Summary: IDA (Uemura et al. 2003) - [3H]dihydrosphingosine labelling shows Csg2 is required for mannosylated sphingolipid synthesis. The step Csg2 participates in is IPC -> MIPC; M(IP)2C is made downstream by Ipt1 and is affected only as a consequence. The more precise process term is MIPC biosynthesis. Reason: Csg2 acts at the MIPC synthase step, not in M(IP)2C formation. Proposed replacements: mannosyl-inositol phosphorylceramide biosynthetic process Supporting Evidence: PMID:12954640 Deletion of the CSG2 gene reduced the Csg1p activity and abolished the Csh1p activity. |
| GO:0006688 glycosphingolipid biosynthetic process | IMP PMID:8063782 Suppressors of the Ca(2+)-sensitive yeast mutant (csg2) iden... | ACCEPT | Summary: IMP (Beeler et al. 1994) - csg2 null mutants have altered sphingolipid metabolism; MIPC is the yeast glycosphingolipid whose synthesis requires Csg2. Supporting Evidence: PMID:8063782 Other scs mutants as well as the csg2 null mutant have altered sphingolipid metabolism. |
| GO:0006874 intracellular calcium ion homeostasis | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR031581, Csg2 family) for intracellular calcium ion homeostasis. Supported for Csg2 by mutant Ca2+ sensitivity and by its ER Ca2+ channel activity. Supporting Evidence: PMID:37349354 Csg2 is localized at the ER membranes and functions as a calcium release channel maintaining the calcium homeostasis in ER. |
| GO:0006874 intracellular calcium ion homeostasis | IMP PMID:7854312 The CLS2 gene encodes a protein with multiple membrane-spann... | ACCEPT | Summary: IMP (Takita et al. 1995) - cls2/csg2 disruption gives a Ca2+-sensitive phenotype. Supporting Evidence: PMID:7854312 A cls2 disruption strain is viable, but shows a Ca(2+)-sensitive phenotype like the original cls2 mutants. |
| GO:0015278 intracellularly gated calcium channel activity | IDA PMID:37349354 The ER calcium channel Csg2 integrates sphingolipid metaboli... | ACCEPT | Summary: IDA (Liu et al. 2023) - purified Csg2 produces stepwise Ca2+ currents in bilayer recordings and mediates ER Ca2+ release in vivo. Supporting Evidence: PMID:37349354 After the addition of the Csg2 protein to the calcium chloride-containing buffer solution, a clear stepwise current increase was observed |
| GO:0019722 calcium-mediated signaling | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Inter-ontology IEA inferred from the calcium channel MF (GO:0015278 -> calcium-mediated signaling). Csg2-mediated ER Ca2+ efflux does affect sphingolipid synthesis and autophagy, but the inference is automatic and the signalling pathway is not defined. Reason: Plausible but generic inference from channel activity. Supporting Evidence: PMID:37349354 Under starvation conditions, deletion of Csg2 causes an increase in ER calcium, which disturbs sphingolipid synthesis |
| GO:0030234 enzyme regulator activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR031581) for enzyme regulator activity. Matches Csg2's role as regulatory subunit of the MIPC synthases. Supporting Evidence: PMID:12954640 Deletion of the CSG2 gene reduced the Csg1p activity and abolished the Csh1p activity. |
| GO:0030234 enzyme regulator activity | IMP PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | ACCEPT | Summary: IMP (Uemura et al. 2003) - deletion of CSG2 reduces Sur1/Csg1 activity and abolishes Csh1 activity. Supporting Evidence: PMID:12954640 Deletion of the CSG2 gene reduced the Csg1p activity and abolished the Csh1p activity. |
| GO:0031501 mannosyltransferase complex | IDA PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | ACCEPT | Summary: IDA (Uemura et al. 2003) - Csg2 is part of the Csg1-Csg2 and Csh1-Csg2 IPC mannosyltransferase complexes. Supporting Evidence: PMID:12954640 two distinct inositol phosphorylceramide mannosyltransferase complexes, Csg1p-Csg2p and Csh1p-Csg2p, exist |
| GO:0031501 mannosyltransferase complex | IPI PMID:12954640 Csg1p and newly identified Csh1p function in mannosylinosito... | ACCEPT | Summary: IPI (Uemura et al. 2003) - same complexes, supported by Csg2 interaction with Csg1 and Csh1. Supporting Evidence: PMID:12954640 We also revealed that Csg2p interacts with both Csg1p and Csh1p. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IMP PMID:37349354 The ER calcium channel Csg2 integrates sphingolipid metaboli... | ACCEPT | Summary: IMP (Liu et al. 2023) - csg2 deletion raises ER luminal Ca2+. Supporting Evidence: PMID:37349354 We show that the ER calcium channel Csg2 is essential for restraining the calcium concentration inside the ER because it directs calcium flux out of the ER. |
| GO:1903514 release of sequestered calcium ion into cytosol by endoplasmic reticulum | IMP PMID:37349354 The ER calcium channel Csg2 integrates sphingolipid metaboli... | ACCEPT | Summary: IMP (Liu et al. 2023) - Csg2 directs Ca2+ flux out of the ER; this is the process its channel activity executes. Supporting Evidence: PMID:37349354 We show that the ER calcium channel Csg2 is essential for restraining the calcium concentration inside the ER because it directs calcium flux out of the ER. |
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Calcium release channel involved in ER calcium homeostasis; integrates ER calcium release with the regulation of sphingolipid metabolism and autophagy; required for mannosylation of inositolphosphorylceramide and for growth at high calcium concentrations; endoplasmic reticulum membrane protein; contains 10 transmembrane domains and a potential Ca2+ EF-hand motif; protein abundance increases in response to DNA replication stress
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