MMM1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:16093310 Large-scale identification of yeast integral membrane protei...	REMOVE	Summary: Generic protein binding from an interaction study (split-ubiquitin membrane yeast two-hybrid screen). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MMM1's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:16093310 by using a modified split-ubiquitin technique
GO:0005515 protein binding	IPI PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet...	REMOVE	Summary: Generic protein binding from an interaction study (Mdm12/Mmm1 beta-barrel assembly study). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MMM1's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:17410204 Mdm12/Mmm1 function after SAM(core) yet before splitting of the major pathway.
GO:0005515 protein binding	IPI PMID:20111053 Mdm10 as a dynamic constituent of the TOB/SAM complex direct...	REMOVE	Summary: Generic protein binding from an interaction study (Mdm10 in TOB/SAM and MMM1 complexes). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MMM1's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:20111053 Mdm10 is distributed in the TOB complex for beta-barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria.
GO:0005515 protein binding	IPI PMID:21825164 The conserved GTPase Gem1 regulates endoplasmic reticulum-mi...	REMOVE	Summary: Generic protein binding from an interaction study (purification of ERMES and identification of Gem1). Reason: Generic protein binding (GO:0005515) conveys no functional information. The interaction itself is not disputed: it reflects MMM1's membership of ERMES (and, for Mdm10, of the SAM complex), which is already captured by the part_of ERMES complex / SAM complex annotations and, functionally, by the tether and lipid transfer activity rows. No more informative molecular function can be read from binary interaction data alone, so the row is removed rather than modified. Supporting Evidence: PMID:21825164 Here we purified ERMES complexes and identified the Ca(2+)-binding Miro GTPase Gem1 as an integral component of ERMES.
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	MARK AS OVER ANNOTATED	Summary: Mitochondrion, from a large-scale proteomic inventory of purified mitochondria. Reason: Mmm1 is an integral ER membrane protein (N-glycosylated lumenal domain, ER-directed TEV accessibility). It co-purifies with mitochondria because ERMES bridges the ER to the outer membrane and the attached ER patches fractionate with mitochondria. The proteomic hit is therefore real but reflects contact-site co-fractionation, not residence in the mitochondrion. Not removed because Mmm1 does sit at the mitochondrial surface as part of a contact-site complex. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005741 mitochondrial outer membrane	HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane...	REMOVE	Summary: Mitochondrial outer membrane, from proteomics of purified outer membranes. Reason: Removed for the same reason as the IDA row for this term (PMID:11266455): Mmm1 is an integral ER membrane protein (N-glycosylated, cleaved by ER-targeted TEV protease), and its presence in outer membrane preparations reflects tight ERMES-mediated association of ER fragments with the outer membrane. Unlike the GO:0005739 mitochondrion HDA row, which is kept as over-annotated because Mmm1 does reside at the mitochondrial surface within the ERMES contact, this term asserts membership of the outer membrane itself, which the ER-insertion evidence contradicts. ER membrane (GO:0005789) remains as the correct location. Supporting Evidence: PMID:16407407 the mitochondrial outer membrane not only contains resident proteins but also accumulates a conserved subclass of preproteins destined for internal mitochondrial compartments PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005741 mitochondrial outer membrane	IDA PMID:11266455 Mmm1p, a mitochondrial outer membrane protein, is connected ...	REMOVE	Summary: Mitochondrial outer membrane, from GFP localization and fractionation (Hobbs et al. 2001), which predates the discovery that Mmm1 is an ER protein. Reason: This localization is directly contradicted by later, more discriminating experiments: Kornmann et al. 2009 showed that Mmm1 is N-glycosylated (requiring lumenal exposure of its N-terminus in the ER), that an ER-targeted TEV protease cleaves it, and that Mmm1-GFP relocalizes to peripheral and perinuclear ER when ERMES is disrupted; they explicitly state that Mmm1 had been misannotated as a mitochondrial protein, partly because of the TEV accessibility assay used in the earlier work. The punctate signal seen by Hobbs et al. is the ERMES focus at the ER-mitochondria interface. SGD already annotates ER membrane from the same paper (EXP), so removing the outer membrane row leaves the correct localization in place. This is a removal for genuine contradiction, made with the full text of both papers available. Supporting Evidence: PMID:11266455 We found that Mmm1p-GFP is located in small, punctate structures on the mitochondrial outer membrane, adjacent to a subset of matrix-localized mitochondrial DNA nucleoids. PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein PMID:19556461 We used the same assay with an ER-targeted TEV protease and confirmed Mmm1 ER-membrane insertion
GO:0005777 peroxisome	HDA PMID:35563734 Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulati...	MARK AS OVER ANNOTATED	Summary: Peroxisome, from a high-throughput screen of strains overexpressing each protein from the TEF2 promoter in a peroxisome-marker background. Reason: Mmm1 is an ER-resident ERMES subunit; nothing in the targeted literature places it in or on peroxisomes. The screen relied on strong constitutive overexpression, and overproduced Mmm1 is known to accumulate as free ER-resident protein (and to alter peroxisome abundance), so a peroxisome-adjacent signal is most plausibly an overexpression artefact or ER-peroxisome proximity. Mmm1 is not named in the cached text; the call rests on the screen's dataset. Not removed because ER-peroxisome and peroxisome-mitochondria contacts involving ERMES subunits are reported. Supporting Evidence: PMID:35563734 we utilized a collection of strains containing a peroxisomal marker in which each protein is expressed from the constitutive and strong TEF2 promoter PMID:30908556 Our results showed that deregulation of peroxisome abundance can only be observed when the Mmm1/Mdm12 stoichiometry is changed either because the Mdm12 protein is absent and the Mmm1/Mdm12 complex cannot be formed, or because Mmm1 is overproduced and free ER-resident Mmm1 protein may accumulate.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that MMM1 family members act in the endoplasmic reticulum. Reason: Correct and consistent with direct evidence that Mmm1 is an integral, N-glycosylated ER membrane protein. The is_active_in qualifier fits: Mmm1 acts from the ER membrane at ER-mitochondria contacts. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005789 endoplasmic reticulum membrane	EXP PMID:11266455 Mmm1p, a mitochondrial outer membrane protein, is connected ...	ACCEPT	Summary: ER membrane (EXP) attributed by SGD to Hobbs et al. 2001. Reason: The location is correct: Mmm1 is an integral ER membrane protein. The 2001 paper interpreted its data as outer-membrane localization, but SGD curators have evidently re-read the topology data (C-terminus facing the cytosol, punctate ER-mitochondria foci) in the light of the later ER assignment. Accepted on the strength of the direct ER evidence. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein PMID:19556461 We used the same assay with an ER-targeted TEV protease and confirmed Mmm1 ER-membrane insertion
GO:0005789 endoplasmic reticulum membrane	EXP PMID:14981098 Mmm2p, a mitochondrial outer membrane protein required for y...	ACCEPT	Summary: ER membrane (EXP) attributed to the Mmm2/Mdm34 paper (Youngman et al. 2004). Reason: Location correct for Mmm1 on the direct evidence of Kornmann et al. 2009. The cited paper studied Mmm1 alongside Mmm2/Mdm34 by fractionation and imaging; the curator's re-interpretation is deferred to. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005789 endoplasmic reticulum membrane	EXP PMID:22250200 A conserved membrane-binding domain targets proteins to orga...	ACCEPT	Summary: ER membrane (EXP) from the study showing that SMP-domain proteins localize to membrane contact sites. Reason: Toulmay and Prinz showed that all seven yeast SMP-domain proteins, including Mmm1, localize to membrane contact sites; Mmm1 is the ER-anchored partner at ER-mitochondria contacts. Location correct. Supporting Evidence: PMID:22250200 We show that all seven proteins that contain this domain in yeast localize to one of three MCSs. PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005789 endoplasmic reticulum membrane	EXP PMID:8089172 MMM1 encodes a mitochondrial outer membrane protein essentia...	ACCEPT	Summary: ER membrane (EXP) attributed to the original MMM1 paper (Burgess et al. 1994). Reason: The 1994 abstract places Mmm1 in the mitochondrial outer membrane with a large cytosolic C-terminal domain; the topology (single TM, cytosolic C-terminus) is retained in the modern model but the membrane is the ER. The SGD curator has re-assigned the location; the ER membrane is correct on direct evidence. Supporting Evidence: PMID:8089172 Mmm1p is located in the mitochondrial outer membrane, with a large carboxyl-terminal domain facing the cytosol. PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0005789 endoplasmic reticulum membrane	IDA PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic...	ACCEPT	Summary: ER membrane (IDA) from N-glycosylation, ER-targeted TEV protease accessibility and ER relocalization of Mmm1-GFP in ERMES mutants. Reason: This is the definitive localization experiment for Mmm1 and the core location of the protein. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein PMID:19556461 We used the same assay with an ER-targeted TEV protease and confirmed Mmm1 ER-membrane insertion
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: ER membrane, combined automated annotation. Reason: Agrees with direct experimental evidence. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0006869 lipid transport	IEA GO_REF:0000117	ACCEPT	Summary: Lipid transport, ARBA automated rule. Reason: Correct but general; the specific process is phospholipid transport / intermembrane lipid transfer, which Mmm1 carries out with Mdm12. Supporting Evidence: PMID:29279306 Therefore, the Mmm1-Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes.
GO:0007005 mitochondrion organization	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Mitochondrion organization (IEA, InterPro) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MMM1 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:19556461 mdm12Δ, mmm1Δ, mdm10Δ, and mdm34Δ strains displayed enlarged and spherical mitochondria as compared with the tubular WT mitochondria PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function.
GO:0007005 mitochondrion organization	IMP PMID:8089172 MMM1 encodes a mitochondrial outer membrane protein essentia...	KEEP AS NON CORE	Summary: Mitochondrion organization (IMP) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MMM1 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:8089172 Cells disrupted in the MMM1 gene are inviable when grown on nonfermentable carbon sources and show abnormal mitochondrial morphology at all temperatures. PMID:19556461 mdm12Δ, mmm1Δ, mdm10Δ, and mdm34Δ strains displayed enlarged and spherical mitochondria as compared with the tubular WT mitochondria PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function.
GO:0007005 mitochondrion organization	NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch...	KEEP AS NON CORE	Summary: Mitochondrion organization (NAS) based on the classic mdm/mmm abnormal mitochondrial morphology phenotype of MMM1 mutants. Reason: Loss of any ERMES subunit converts the tubular mitochondrial network into a few giant spherical mitochondria, which is how these genes were discovered. The phenotype is real, but it is largely a downstream consequence of losing ER-mitochondria tethering and lipid supply: an artificial tether restores morphology of mdm12 and mdm34 mutants, and dominant VPS13 alleles suppress ERMES-deficiency phenotypes. The term is broad and correct at the level of necessity, but it is not the core activity, so it is kept as non-core rather than removed. Supporting Evidence: PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function.
GO:0008289 lipid binding	IBA GO_REF:0000033	ACCEPT	Summary: Lipid binding inferred phylogenetically for the SMP-domain MMM1 family. Reason: Sound node placement: lipid binding is the ancestral property of SMP/TULIP domains and is directly demonstrated for Mmm1, whose SMP domain binds two glycerophospholipids in its hydrophobic cavity. Phospholipid binding would be more specific, but the broader term is not wrong. Supporting Evidence: PMID:29078410 Mmm1 binds two phospholipids inside the hydrophobic cavity PMID:26056272 Furthermore, these two SMP domains bind phospholipids and display a strong preference for phosphatidylcholines
GO:0008289 lipid binding	IEA GO_REF:0000002	ACCEPT	Summary: Lipid binding from InterPro (SMP-LTD domain). Reason: Correct; experimentally confirmed for the Mmm1 SMP domain. Supporting Evidence: PMID:29078410 Mmm1 binds two phospholipids inside the hydrophobic cavity
GO:0012505 endomembrane system	IEA GO_REF:0000117	ACCEPT	Summary: Endomembrane system (IEA, ARBA rule). Reason: MMM1 is an integral ER membrane protein; the ER is part of the endomembrane system, so this broad automated term is correct. Supporting Evidence: PMID:19556461 indicating that Mmm1 is N-glycosylated and therefore is an integral ER membrane protein that was misannotated as a mitochondrial protein
GO:0015914 phospholipid transport	IGI PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic...	ACCEPT	Summary: Phospholipid transport (IGI) for MMM1. Reason: ERMES mediates non-vesicular phospholipid transfer from the ER to mitochondria: ERMES mutants show a two- to fivefold reduction in PS-to-PC conversion, isolated membranes lacking Mmm1, Mdm12 or Mdm34 are defective in PS transport from ER to mitochondria, the purified Mmm1-Mdm12 complex transfers phospholipids between liposomes, and in vivo mass-tagging (METALIC) shows ERMES transport activity in living cells. An earlier in vivo radiolabelling study (Nguyen et al. 2012, PMID:22409400) found PS-to-PE conversion unaffected in ERMES mutants; this is now generally explained by redundant routes (Vps13-Mcp1 at vacuole-mitochondria contacts) rather than by absence of ERMES transfer activity. Supporting Evidence: PMID:19556461 Mutants of ERMES showed a two- to fivefold reduction in PS-to-PC conversion rate PMID:19556461 Thus, ERMES-mediated ER-mitochondria connections are necessary for efficient inter-organellar phospholipid exchange.
GO:0015914 phospholipid transport	IMP PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic...	ACCEPT	Summary: Phospholipid transport (IMP) for MMM1. Reason: ERMES mediates non-vesicular phospholipid transfer from the ER to mitochondria: ERMES mutants show a two- to fivefold reduction in PS-to-PC conversion, isolated membranes lacking Mmm1, Mdm12 or Mdm34 are defective in PS transport from ER to mitochondria, the purified Mmm1-Mdm12 complex transfers phospholipids between liposomes, and in vivo mass-tagging (METALIC) shows ERMES transport activity in living cells. An earlier in vivo radiolabelling study (Nguyen et al. 2012, PMID:22409400) found PS-to-PE conversion unaffected in ERMES mutants; this is now generally explained by redundant routes (Vps13-Mcp1 at vacuole-mitochondria contacts) rather than by absence of ERMES transfer activity. Supporting Evidence: PMID:19556461 Mutants of ERMES showed a two- to fivefold reduction in PS-to-PC conversion rate PMID:19556461 Thus, ERMES-mediated ER-mitochondria connections are necessary for efficient inter-organellar phospholipid exchange.
GO:0015914 phospholipid transport	IMP PMID:29279306 Structure-function insights into direct lipid transfer betwe...	ACCEPT	Summary: Phospholipid transport (IMP, acts_upstream_of_or_within) for MMM1. Reason: ERMES mediates non-vesicular phospholipid transfer from the ER to mitochondria: ERMES mutants show a two- to fivefold reduction in PS-to-PC conversion, isolated membranes lacking Mmm1, Mdm12 or Mdm34 are defective in PS transport from ER to mitochondria, the purified Mmm1-Mdm12 complex transfers phospholipids between liposomes, and in vivo mass-tagging (METALIC) shows ERMES transport activity in living cells. An earlier in vivo radiolabelling study (Nguyen et al. 2012, PMID:22409400) found PS-to-PE conversion unaffected in ERMES mutants; this is now generally explained by redundant routes (Vps13-Mcp1 at vacuole-mitochondria contacts) rather than by absence of ERMES transfer activity. Kawano et al. showed that SMP-pocket mutations in Mmm1 impair both liposome transfer and ERMES-dependent PS transport; Mmm1 does the work of the transfer, so the involvement is direct. Supporting Evidence: PMID:29279306 Mutations in Mmm1 or Mdm12 impaired the lipid transfer activities of the Mdm12-Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro. PMID:29279306 Therefore, the Mmm1-Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes.
GO:0015917 aminophospholipid transport	IBA GO_REF:0000033	ACCEPT	Summary: Aminophospholipid transport, phylogenetic inference. Reason: Consistent with direct evidence that Mmm1 is required for phosphatidylserine transport from the ER to mitochondria and that the Mmm1-Mdm12 complex transfers PS and PE between liposomes. Supporting Evidence: PMID:27469264 In the absence of Mmm1, Mdm12 or Mdm34 the PS transport from the ER to mitochondria was significantly impaired PMID:29279306 Mutations in Mmm1 or Mdm12 impaired the lipid transfer activities of the Mdm12-Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro.
GO:0015917 aminophospholipid transport	IMP PMID:27469264 A phospholipid transfer function of ER-mitochondria encounte...	ACCEPT	Summary: Aminophospholipid (phosphatidylserine) transport from the ER to mitochondria impaired in mmm1 membranes in an in vitro organelle assay. Reason: Direct mutant evidence; Mmm1 is a lipid-transferring subunit, so this is participation not mere necessity. Note that PE export from mitochondria to the ER was not ERMES-dependent in this assay, so the direction is ER-to-mitochondria. Supporting Evidence: PMID:27469264 In the absence of Mmm1, Mdm12 or Mdm34 the PS transport from the ER to mitochondria was significantly impaired PMID:27469264 Taken together, we conclude that ERMES plays a critical role in facilitating the PS transport from the ER to mitochondria. PMID:27469264 It is thus likely that the PE transport is primarily mediated by uncharacterized factors other than ERMES.
GO:0032865 ERMES complex	IBA GO_REF:0000033	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IBA evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0032865 ERMES complex	IDA PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet...	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IDA evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0032865 ERMES complex	IDA PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic...	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IDA evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0032865 ERMES complex	IEA GO_REF:0000120	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IEA evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0032865 ERMES complex	IPI PMID:13679517 A protein complex containing Mdm10p, Mdm12p, and Mmm1p links...	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0032865 ERMES complex	IPI PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch...	ACCEPT	Summary: MMM1 is a core subunit of the ER-mitochondria encounter structure (ERMES); IPI evidence. Reason: ERMES membership of MMM1 is among the best-established facts about this protein: the four core subunits (Mmm1, Mdm10, Mdm12, Mdm34) co-purify, co-immunoprecipitate, co-localize in a few discrete foci at ER-mitochondria contacts and are mutually required for focus formation. Gem1 is a fifth, regulatory subunit. This is the central cellular component for the gene and is used as in_complex in core_functions. Supporting Evidence: PMID:19556461 We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site	IDA PMID:37366411 Complementation Assay Using Fusion of Split-GFP and TurboID ...	ACCEPT	Summary: Proximity biotinylation (CsFiND split-GFP/TurboID) at ER-mitochondria contacts labelled MMM1. Reason: ERMES is the defining tether of yeast ER-mitochondria contact sites and MMM1 acts there. The CsFiND reporter specifically biotinylated Mmm1, Mdm12 and Mdm34 (Mdm10 was not detected). The is_active_in qualifier is appropriate; this is the core location for the tethering and lipid-transfer function. Supporting Evidence: PMID:37366411 showed CsFiND specifically biotinylated three of the four ERMES core subunits (Mmm1, Mdm12, and Mdm34)
GO:0045040 protein insertion into mitochondrial outer membrane	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: Protein insertion into mitochondrial outer membrane, UniRule. Reason: Derived from the Meisinger et al. 2007 finding that Mdm12/Mmm1 act in a late step of beta-barrel assembly. The experimental basis is mutant (necessity) data; given that ERMES mutants have pleiotropic membrane-lipid defects that can secondarily impair outer membrane protein biogenesis, Mmm1's involvement may be indirect. Kept, deferring to the experimental record, but not core. Supporting Evidence: PMID:17410204 Mdm12/Mmm1 function after SAM(core) yet before splitting of the major pathway. PMID:17410204 Mdm12/Mmm1 have been known for their role in maintenance of mitochondrial morphology but we reveal assembly of beta-barrel proteins as their primary function.
GO:0045040 protein insertion into mitochondrial outer membrane	IMP PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet...	KEEP AS NON CORE	Summary: Protein insertion into mitochondrial outer membrane (IMP), Meisinger et al. 2007. Reason: Mitochondria lacking Mdm12/Mmm1 accumulate beta-barrel precursors after the SAM core step, and the authors proposed beta-barrel assembly as the primary function. Subsequent work identified ER-mitochondria tethering and lipid transfer as the primary ERMES activity, with bypass suppressors rescuing the pleiotropic phenotypes, so Mmm1 is not known to perform a step of insertion itself. The abstract-only cache does not allow the data to be re-examined, so the curator call is kept as non-core. Supporting Evidence: PMID:17410204 Mdm12/Mmm1 function after SAM(core) yet before splitting of the major pathway. PMID:17410204 Mdm12/Mmm1 have been known for their role in maintenance of mitochondrial morphology but we reveal assembly of beta-barrel proteins as their primary function. PMID:26370498 The fact that it suppresses ERMES mtDNA defects indicates that these are secondary to the loss of a primary ERMES function.
GO:0055091 phospholipid homeostasis	NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch...	KEEP AS NON CORE	Summary: Phospholipid homeostasis (NAS) from the ERMES composition/topology study. Reason: ERMES mutants show reduced cardiolipin and slowed PS-to-PC conversion; these are consequences of impaired ER-to-mitochondria phospholipid transfer, which MMM1 executes as part of ERMES. The homeostasis term is a reasonable but indirect description of that role; the direct process is captured by phospholipid transport / intermembrane lipid transfer. Supporting Evidence: PMID:21945531 ERMES represents a platform that integrates components with functions in formation of ER-mitochondria junctions, maintenance of mitochondrial morphology, protein biogenesis and calcium binding PMID:19556461 A reduced rate of lipid exchange in turn slows down amino-glycerophospholipid turnover, which results in impaired CL synthesis
GO:0070096 mitochondrial outer membrane translocase complex assembly	IMP PMID:17410204 The morphology proteins Mdm12/Mmm1 function in the major bet...	KEEP AS NON CORE	Summary: Mitochondrial outer membrane translocase complex assembly (IMP), Meisinger et al. 2007. Reason: Same reasoning as the protein insertion row: Tom40 assembly is impaired in mmm1 mitochondria, but the evidence is necessity, and an indirect contribution via membrane lipid composition cannot be excluded. Mdm10, not Mmm1, is the SAM-associated subunit that acts directly in TOM assembly. Supporting Evidence: PMID:17410204 Mdm12/Mmm1 function after SAM(core) yet before splitting of the major pathway. PMID:17410204 Mdm10, which functions in the Tom40-specific route, can associate with SAM(core) as well as Mdm12/Mmm1 to form distinct assembly complexes
GO:0098799 outer mitochondrial membrane protein complex	NAS PMID:21945531 Composition and topology of the endoplasmic reticulum-mitoch...	ACCEPT	Summary: Outer mitochondrial membrane protein complex (NAS), a general parent of ERMES complex. Reason: In GO, ERMES complex (GO:0032865) is a descendant of outer mitochondrial membrane protein complex (GO:0098799) (ancestor chain verified in QuickGO), so this NAS row is a correct but less specific restatement of MMM1's ERMES membership. Redundant, not wrong. Supporting Evidence: PMID:21945531 Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis.
GO:0120009 intermembrane lipid transfer	IEA GO_REF:0000108	ACCEPT	Summary: Intermembrane lipid transfer, inferred by GO logic from the lipid transfer activity annotation. Reason: Accurate and the best process term for Mmm1: with Mdm12 it extracts phospholipids from one membrane and delivers them to another, at ER-mitochondria contacts. Supporting Evidence: PMID:29279306 Therefore, the Mmm1-Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes. PMID:35654841 we show that the ERMES and Vps13-Mcp1 complexes have transport activity in vivo
GO:0120013 lipid transfer activity	IBA GO_REF:0000033	ACCEPT	Summary: Lipid transfer activity (contributes_to), phylogenetic inference. Reason: Sound node placement; matches the direct IDA evidence that the Mmm1-Mdm12 complex, not either protein alone, has efficient transfer activity. The contributes_to qualifier is correct. Supporting Evidence: PMID:29279306 This indicates that the lipid transfer activity of the Mmm1s–Mdm12 complex between membranes arises from the cooperation of Mmm1s and Mdm12.
GO:0120013 lipid transfer activity	IDA PMID:29279306 Structure-function insights into direct lipid transfer betwe...	ACCEPT	Summary: Lipid transfer activity (contributes_to) from liposome transfer assays with purified Mmm1-Mdm12. Reason: Core molecular function. Mmm1's SMP domain alone has only weak transfer activity; the Mmm1-Mdm12 complex is efficient and both pockets are required, so contributes_to is exactly right. The substrates are glycerophospholipids (NBD-PE and NBD-PS were transferred), so phospholipid transfer activity (GO:0120014) is used in core_functions as the more specific term. Supporting Evidence: PMID:29279306 In contrast, Mdm12 in a complex with Mmm1 mediated efficient lipid transfer between liposomes. PMID:29279306 This indicates that the lipid transfer activity of the Mmm1s–Mdm12 complex between membranes arises from the cooperation of Mmm1s and Mdm12. PMID:29279306 However, when tested in vitro, purified free KlMdm12 alone or Mmm1s as a purified fusion protein (MBP-HMmm1s) is capable of extracting phospholipid from donor liposomes and transferring it to acceptor liposomes, but this lipid transfer activity is very low.
GO:0140474 mitochondrion-endoplasmic reticulum membrane tether activity	IDA PMID:19556461 An ER-mitochondria tethering complex revealed by a synthetic...	ACCEPT	Summary: Mitochondrion-ER membrane tether activity for MMM1, from the synthetic-tether (ChiMERA) complementation screen that defined ERMES. Reason: Kornmann et al. 2009 showed that the Mmm1/Mdm10/Mdm12/Mdm34 complex physically links the ER and the mitochondrial outer membrane and that its loss is partly bypassed by an artificial ER-mitochondria tether. Mmm1 is the ER-membrane anchor of the bridge; it relocalizes to the ER when any other subunit is missing. The MF term describes the activity of the assembled bridge, and each subunit contributes a physically necessary part of it (ER anchor, OM anchor, or the SMP-domain bridge), so the annotation is accepted for every core subunit. GO:1990456 (the former BP for this tethering) was obsoleted in favour of this MF term (verified in QuickGO). Supporting Evidence: PMID:19556461 Thus, one core molecular function of the Mmm1/Mdm10/Mdm12/Mdm34 complex is to connect ER and mitochondria, which can be bypassed by expressing a synthetic tether. PMID:19556461 ERMES consists of the ER-resident membrane protein Mmm1 and the OMM-resident β-barrel protein Mdm10

Gene Description

Existing Annotations Review

Core Functions

ER-anchored SMP-domain subunit of ERMES that, together with Mdm12, extracts glycerophospholipids from the ER membrane and transfers them toward the mitochondrial outer membrane at ER-mitochondria contact sites (phosphatidylserine export from the ER being the best documented flux).

ER membrane anchor of the ERMES bridge that physically tethers the ER to the mitochondrial outer membrane.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

SGD

SGD gene description for MMM1 (yeast)

📚 Additional Documentation

Notes

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