MSC2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005385 zinc ion transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Zinc ion transmembrane transporter activity propagated by PAINT from node PTN000169508, to which MSC2 itself, S. pombe Cis4 and vertebrate ZnT5/ZnT7 are experimental donors. Reason: MSC2 sits in PANTHER subfamily PTHR45755:SF4 with Cis4 and is inside the clade that inherited the function. MSC2 appearing among the node's donors reflects its own experimental grounding (PMID:15277543, PMID:11058603). Msc2 keeps the complete His-Asp-His-Asp transmembrane zinc site of transport-competent CDF proteins, whereas its partner Zrg17 has lost it. This makes Msc2 the predicted zinc-carrying subunit of the Msc2-Zrg17 heteromer. Direct flux assays are still lacking, so the activity rests on genetics, family membership and the conserved site. Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER PMID:15961382 we propose that Msc2p and Zrg17p form a heteromeric zinc transport complex in the ER membrane file:yeast/MSC2/MSC2-bioinformatics/RESULTS.md Msc2 has a complete His-Asp-His-Asp site A, the same as its PTHR45755:SF4 relatives PMID:21250939 Direct assays of Zrg17/Msc2 complex activity, e.g. 65Zn transport assays, have not yet been developed.
GO:0005385 zinc ion transmembrane transporter activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping from IPR045316 (Msc2-like) to zinc ion transmembrane transporter activity. Reason: This agrees with the IBA and the experimental evidence. The Msc2-like signature defines the ZnT5/Msc2/Cis4 clade of CDF zinc transporters, and the target keeps the zinc-binding site A. Supporting Evidence: file:yeast/MSC2/MSC2-uniprot.txt Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily. file:yeast/MSC2/MSC2-bioinformatics/RESULTS.md Msc2 has a complete His-Asp-His-Asp site A, the same as its PTHR45755:SF4 relatives
GO:0005385 zinc ion transmembrane transporter activity	IMP PMID:11058603 The yeast gene MSC2, a member of the cation diffusion facili...	ACCEPT	Summary: msc2 deletion alters cellular zinc content and distribution, which places Msc2 as a zinc transporter. Reason: The cached record is abstract-only. The phenotype is zinc-specific (iron- and copper-regulated genes are unaffected), and later work on the same protein (PMID:15277543, PMID:15961382) supports zinc transport across the ER membrane. Li & Kaplan proposed that zinc moves from the nucleus/ER to the cytosol, but later work revised the direction to import into the ER. The MF term is the same either way, so the curator's annotation stands. Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells. PMID:15277543 Msc2 is one route of zinc entry into the ER
GO:0005515 protein binding	IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro...	REMOVE	Summary: High-throughput interaction screen detecting binding between Msc2 and Zrg17 (P53735). Reason: Under the repository protein-binding policy a bare GO:0005515 annotation is uninformative and is removed. The interaction itself is real and biologically important: Msc2 and Zrg17 co-immunoprecipitate and form a heteromeric zinc transport complex in the ER membrane (PMID:15961382). That information is captured in core_functions (partner Zrg17) and in the transporter MF. Removing this row does not mean the interaction is false. Supporting Evidence: PMID:15961382 Msc2p and Zrg17p physically interact with each other, as determined by co-immunoprecipitation.
GO:0005515 protein binding	IPI PMID:16093310 Large-scale identification of yeast integral membrane protei...	REMOVE	Summary: High-throughput interaction screen detecting binding between Msc2 and Zrg17 (P53735). Reason: Under the repository protein-binding policy a bare GO:0005515 annotation is uninformative and is removed. The interaction itself is real and biologically important: Msc2 and Zrg17 co-immunoprecipitate and form a heteromeric zinc transport complex in the ER membrane (PMID:15961382). That information is captured in core_functions (partner Zrg17) and in the transporter MF. Removing this row does not mean the interaction is false. Supporting Evidence: PMID:15961382 Msc2p and Zrg17p physically interact with each other, as determined by co-immunoprecipitation.
GO:0005515 protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	REMOVE	Summary: High-throughput interaction screen detecting binding between Msc2 and Zrg17 (P53735). Reason: Under the repository protein-binding policy a bare GO:0005515 annotation is uninformative and is removed. The interaction itself is real and biologically important: Msc2 and Zrg17 co-immunoprecipitate and form a heteromeric zinc transport complex in the ER membrane (PMID:15961382). That information is captured in core_functions (partner Zrg17) and in the transporter MF. Removing this row does not mean the interaction is false. Supporting Evidence: PMID:15961382 Msc2p and Zrg17p physically interact with each other, as determined by co-immunoprecipitation.
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: High-throughput interaction screen detecting binding between Msc2 and Zrg17 (P53735). Reason: Under the repository protein-binding policy a bare GO:0005515 annotation is uninformative and is removed. The interaction itself is real and biologically important: Msc2 and Zrg17 co-immunoprecipitate and form a heteromeric zinc transport complex in the ER membrane (PMID:15961382). That information is captured in core_functions (partner Zrg17) and in the transporter MF. Removing this row does not mean the interaction is false. Supporting Evidence: PMID:15961382 Msc2p and Zrg17p physically interact with each other, as determined by co-immunoprecipitation.
GO:0005783 endoplasmic reticulum	HDA PMID:26928762 One library to make them all: streamlining the creation of y...	MODIFY	Summary: Genome-wide SWAT-tag localization places Msc2 in the endoplasmic reticulum. Reason: ER localization is correct and agrees with targeted studies. Msc2 is a multi-pass (14 TM) integral membrane protein, so the more specific term endoplasmic reticulum membrane (GO:0005789), already carried by the gene, applies. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. file:yeast/MSC2/MSC2-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269\|PubMed:14562095}; Multi-pass membrane protein
GO:0005783 endoplasmic reticulum	IDA PMID:15277543 Zinc and the Msc2 zinc transporter protein are required for ...	MODIFY	Summary: Msc2 expressed from its own promoter cofractionates with ER markers and shows the Mg2+-dependent ER density shift. Reason: ER localization is well supported. The assay is a membrane fractionation of an integral membrane protein, so endoplasmic reticulum membrane (GO:0005789) is the appropriately specific term. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location mapping (SL-0097) to endoplasmic reticulum membrane, from GFP localization (Huh et al. 2003). Reason: This is the principal location of Msc2 in S. cerevisiae, supported by GFP localization, epitope-tag localization and Mg2+-shift fractionation, and it is where the Msc2-Zrg17 complex is proposed to act. Supporting Evidence: file:yeast/MSC2/MSC2-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269\|PubMed:14562095}; Multi-pass membrane protein PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. PMID:15961382 we propose that Msc2p and Zrg17p form a heteromeric zinc transport complex in the ER membrane
GO:0005794 Golgi apparatus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Golgi apparatus (is_active_in) propagated from the deep PAINT node PTN000169412, whose donors include Cis4 and vertebrate ZnT5/ZnT7. Reason: The Golgi location is real for the donors (cis-Golgi for S. pombe Cis4, Golgi for ZnT5/ZnT7). In S. cerevisiae the active pool of Msc2 is in the ER. Fractionation hints at a minor pool in later secretory compartments ("perhaps the Golgi"), but Golgi function was unaffected in msc2 mutants. Saying the transporter is active in the Golgi of budding yeast goes beyond the species-specific evidence. This looks like lineage-specific relocalization rather than loss of the core function. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000169412 SUPPORTS SOURCE BUT NOT TARGET Golgi apparatus is experimentally grounded for donors such as S. pombe Cis4 and vertebrate ZnT5/ZnT7, but budding-yeast Msc2 acts in the ER membrane; only a minor, unconfirmed post-ER pool was seen by fractionation. Supporting Evidence: PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. PMID:15277543 suggests that some protein may also be found in later compartments of the secretory pathway, perhaps the Golgi PMID:18199682 Cis4 localized at the cis-Golgi
GO:0006812 monoatomic cation transport	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping from the generic Cation_efflux domain (IPR002524). Reason: This is correct but very general. The substrate (zinc) and the direction and compartment (cytosol into ER lumen) are established, so the process is zinc ion import into endoplasmic reticulum (GO:0140209), a descendant of monoatomic cation transport. Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER PMID:15961382 we propose that Msc2p and Zrg17p form a heteromeric zinc transport complex in the ER membrane
GO:0006829 zinc ion transport	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping from IPR045316 (Msc2-like) to zinc ion transport. Reason: This is correct but general. Msc2 mediates zinc entry into the ER, so the specific descendant zinc ion import into endoplasmic reticulum (GO:0140209) applies, consistent with the IMP row for the same term. Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER
GO:0006829 zinc ion transport	IMP PMID:15277543 Zinc and the Msc2 zinc transporter protein are required for ...	MODIFY	Summary: Ellis et al. show that Msc2 is one route of zinc entry into the ER: msc2 mutants have exacerbated UPR induction and ERAD defects in low zinc that are suppressed by zinc. Reason: The paper's conclusion is directional and compartment-specific (cytosol into ER lumen), and GO now has a term for exactly that: zinc ion import into endoplasmic reticulum (GO:0140209, is_a zinc ion transport via zinc ion import into organelle). The SGD annotation (2004) predates the term, so this is a refinement of the curator's call, not a reversal. Msc2 itself is the transporter, so it does the work of the process. The UPR and ERAD defects are downstream consequences and are not annotated as process participation. Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment.
GO:0006882 intracellular zinc ion homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: Intracellular zinc ion homeostasis propagated from PTN000169508, with MSC2 among the experimental donors. Reason: Msc2 moves zinc between cytosol and the ER lumen and so directly contributes to how zinc is distributed between compartments. msc2 cells have altered total and nuclear-fraction zinc and altered Zap1 target expression. Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells. PMID:11058603 The deletion strain accumulated excess Zn2+ in nuclei-enriched membrane fractions PMID:15277543 Msc2 is one route of zinc entry into the ER
GO:0006882 intracellular zinc ion homeostasis	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping from IPR045316 to intracellular zinc ion homeostasis. Reason: Consistent with the IBA and IMP rows for the same term. Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells.
GO:0006882 intracellular zinc ion homeostasis	IMP PMID:11058603 The yeast gene MSC2, a member of the cation diffusion facili...	ACCEPT	Summary: msc2 deletion increases cellular zinc, causes excess zinc in nuclei-enriched membrane fractions, and lowers expression of Zap1-regulated genes. Reason: This is direct genetic evidence that Msc2 affects the intracellular distribution of zinc. As a zinc transporter it performs part of this homeostatic process rather than being an indirect requirement. The cached record is abstract-only, but the abstract states the key findings. Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells. PMID:11058603 The deletion strain accumulated excess Zn2+ in nuclei-enriched membrane fractions
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	KEEP AS NON CORE	Summary: Zinc proteome bioinformatic prediction listing Msc2 as a potential zinc-binding protein. Reason: Msc2 is predicted to bind zinc: it keeps the complete transmembrane His-Asp-His-Asp site A of CDF transporters. Binding of the transported substrate is part of transporter activity rather than a separate function, so this row is kept as non-core beside the accepted zinc ion transmembrane transporter activity. Supporting Evidence: file:yeast/MSC2/MSC2-bioinformatics/RESULTS.md Msc2 has a complete His-Asp-His-Asp site A, the same as its PTHR45755:SF4 relatives
GO:0008324 monoatomic cation transmembrane transporter activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping from the generic Cation_efflux domain to monoatomic cation transmembrane transporter activity. Reason: This is correct but general. The substrate is zinc, so the specific descendant zinc ion transmembrane transporter activity (GO:0005385), already accepted for this gene, should be used. Proposed replacements: zinc ion transmembrane transporter activity Supporting Evidence: file:yeast/MSC2/MSC2-bioinformatics/RESULTS.md Msc2 has a complete His-Asp-His-Asp site A, the same as its PTHR45755:SF4 relatives PMID:15277543 Msc2 is one route of zinc entry into the ER
GO:0016020 membrane	IEA GO_REF:0000002	MODIFY	Summary: Generic membrane location from the Cation_efflux domain. Reason: Correct but uninformative. The membrane is the ER membrane (GO:0005789), already carried by the gene. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:yeast/MSC2/MSC2-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269\|PubMed:14562095}; Multi-pass membrane protein PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment.
GO:0030003 intracellular monoatomic cation homeostasis	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning prediction of intracellular monoatomic cation homeostasis. Reason: The general cation-homeostasis claim is sound but the ion is known. Use intracellular zinc ion homeostasis (GO:0006882), which the gene carries by IMP and IBA. Proposed replacements: intracellular zinc ion homeostasis Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells.
GO:0031410 cytoplasmic vesicle	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Cytoplasmic vesicle (is_active_in) propagated from PTN000169412, based on mammalian ZnT5 and Dictyostelium donors. Reason: No study places Msc2 in cytoplasmic vesicles in S. cerevisiae. The protein localizes to the ER and nuclear envelope. A vesicular pool cannot be excluded, since ER-to-Golgi trafficking would carry the protein through vesicles, but an active vesicular location is not supported for this species. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000169412 SUPPORTS SOURCE BUT NOT TARGET Cytoplasmic vesicle comes from mammalian and Dictyostelium donors; no study places S. cerevisiae Msc2 in vesicles, and its active pool is in the ER membrane. Supporting Evidence: PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. PMID:11058603 An epitope-tagged Msc2p was localized to the endoplasmic reticulum/nucleus.
GO:0031965 nuclear membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping (SL-0182) to nuclear membrane, from GFP localization. Reason: The nuclear envelope is continuous with the ER, and both GFP and epitope-tag studies report ER/nuclear-periphery staining. The location is correct but is a facet of the ER-membrane localization rather than a distinct site of function. Supporting Evidence: file:yeast/MSC2/MSC2-uniprot.txt Nucleus membrane {ECO:0000269\|PubMed:14562095} PMID:11058603 An epitope-tagged Msc2p was localized to the endoplasmic reticulum/nucleus.
GO:0055085 transmembrane transport	IEA GO_REF:0000002	MODIFY	Summary: Generic transmembrane transport from the Cation_efflux domain. Reason: Correct but very general. Use the specific descendant zinc ion import into endoplasmic reticulum (GO:0140209). Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER
GO:0055085 transmembrane transport	IMP PMID:15277543 Zinc and the Msc2 zinc transporter protein are required for ...	MODIFY	Summary: Transmembrane transport inferred from the msc2 mutant phenotypes in Ellis et al. 2004. Reason: The study supports a specific transmembrane transport process, zinc entry into the ER. GO:0140209 zinc ion import into endoplasmic reticulum is a descendant of transmembrane transport and captures the finding exactly. Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment.
GO:0098771 inorganic ion homeostasis	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning prediction of inorganic ion homeostasis. Reason: Sound but general. The ion is zinc, so use intracellular zinc ion homeostasis (GO:0006882). Proposed replacements: intracellular zinc ion homeostasis Supporting Evidence: PMID:11058603 Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells.
GO:1904257 zinc ion import into Golgi lumen	IBA GO_REF:0000033	MODIFY	Summary: Zinc ion import into Golgi lumen propagated from PTN000169508, based on Cis4 and vertebrate ZnT5/ZnT7, whose active pools are Golgi. Reason: The inherited activity (moving cytosolic zinc into the lumen of the early secretory pathway) is right for Msc2. In S. cerevisiae, though, the compartment shown experimentally is the ER, not the Golgi: Msc2 expressed at normal levels is in the ER and is one route of zinc entry into the ER. MSC2 is a donor to this node for the MF and homeostasis terms but has no Golgi-import evidence of its own. This is a lateral compartment correction to zinc ion import into endoplasmic reticulum (GO:0140209). A minor Golgi role cannot be excluded. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000169508 SUPPORTS SOURCE BUT NOT TARGET The node correctly carries zinc import into the early secretory pathway, but the Golgi compartment reflects Cis4 and ZnT5/ZnT7. Budding-yeast Msc2 imports zinc into the ER, so the activity transfers and the compartment does not. Proposed replacements: zinc ion import into endoplasmic reticulum Supporting Evidence: PMID:15277543 Msc2 is one route of zinc entry into the ER PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. PMID:15277543 suggests that some protein may also be found in later compartments of the secretory pathway, perhaps the Golgi
GO:1990674 Golgi cis cisterna membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Golgi cis cisterna membrane (is_active_in) propagated from PTN000169508, reflecting the cis-Golgi localization of S. pombe Cis4 and mammalian donors. Reason: The cis-Golgi assignment is experimentally grounded for Cis4 but is lineage-specific. Budding-yeast Msc2 localizes to the ER membrane when expressed at physiological levels, and no study places it in cis-Golgi cisternae. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000169508 SUPPORTS SOURCE BUT NOT TARGET cis-Golgi cisterna membrane is grounded in Cis4 and mammalian donors; budding-yeast Msc2 localizes to the ER membrane at physiological expression. Supporting Evidence: PMID:15277543 Because Msc2 colocalizes with an ER marker protein and shows the characteristic ER Mg2+ shift, these studies strongly support the localization of Msc2 to that compartment. PMID:18199682 Cis4 localized at the cis-Golgi

Gene Description

Existing Annotations Review

Core Functions

Zinc transporter subunit of the Msc2-Zrg17 heteromeric CDF complex that imports cytosolic zinc into the ER lumen, supplying zinc for ER function, particularly under zinc limitation.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

SGD

SGD gene description for MSC2 (yeast)

📚 Additional Documentation

Notes

Bioinformatics Results

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