Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0022857 transmembrane transporter activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Generic transmembrane transporter activity propagated phylogenetically from the legacy "membrane magnesium transporter" family inference. The verified function of MMGT1 is as an EMC insertase subunit, not as a solute transporter. Reason: No experimental evidence that human MMGT1 transports a solute; the transporter assignment derives from a legacy family name and is superseded by the EMC insertase role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0005769 early endosome	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic early-endosome localization, ultimately derived from the rodent ortholog. The experimentally verified compartment is the ER membrane. Reason: Possible minor localization carried over by similarity but peripheral to the core ER-membrane EMC site of action. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Early endosome membrane
GO:0005794 Golgi apparatus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic Golgi localization derived from the rodent ortholog. The core EMC site of action is the ER membrane. Reason: Possible minor localization by similarity but peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Golgi
GO:0005886 plasma membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic plasma-membrane localization, weakly supported and most likely reflecting the transporter-family inference. MMGT1 acts in the ER membrane as an EMC subunit. Reason: Not supported by experimental evidence for the human protein; inconsistent with the ER-membrane EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0072546 EMC complex	IBA GO_REF:0000033	ACCEPT	Summary: MMGT1/EMC5 is a constitutive subunit of the ER membrane protein complex; phylogenetic assignment is consistent with direct experimental and structural evidence. Core structural identity. Reason: EMC complex membership is the core cellular-component identity of MMGT1; supported by IDA, cryo-EM structures, and the conserved EMC5 family. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Component of the ER membrane protein complex (EMC).
GO:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of a Golgi membrane location from the UniProt subcellular location vocabulary, itself a By-similarity assignment from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the core ER-membrane EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Golgi
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for MMGT1. Reason: Correct core location; redundant with experimental EXP/IDA evidence. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006824 cobalt ion transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inter-ontology electronic inference of cobalt ion transport, derived ultimately from the legacy metal-transporter family assignment. No experimental support for cobalt transport by human MMGT1. Reason: Speculative metal-transport process inferred from a contested family name; not the verified EMC insertase function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0012505 endomembrane system	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning assignment to the endomembrane system, a generic parent of the specific ER membrane localization. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0031901 early endosome membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of early endosome membrane localization from UniProt, a By-similarity assignment from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Early endosome membrane
GO:0034755 iron ion transmembrane transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inter-ontology electronic inference of iron transmembrane transport from the legacy metal-transporter family. No experimental support for iron transport by human MMGT1. Reason: Speculative metal-transport process; not the verified EMC insertase function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0055085 transmembrane transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Generic transmembrane transport process inferred electronically from the transporter-activity assignment. Not the verified EMC insertase function. Reason: Derived from the contested transporter-family inference; superseded by the EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:1903830 magnesium ion transmembrane transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inter-ontology electronic inference of magnesium transmembrane transport. UniProt records only a By-similarity possibility of Mg(2+) transport for human MMGT1; the consensus role is as an EMC insertase subunit. Reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0005515 protein binding	IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ...	KEEP AS NON CORE	Summary: IntAct interactions from the foundational ERAD-network mapping study that first defined the EMC, including the EMC subunits EMC2 and EMC6. Genuine EMC partnership, but bare protein binding is uninformative. Reason: Real EMC partner interactions but the bare protein binding term is uninformative per curation guidelines. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q9BV81: EMC6
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	KEEP AS NON CORE	Summary: Quantitative interactome (stoichiometry/abundance) capture; reflects EMC and membrane-protein partnerships. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q15006: EMC2
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: High-throughput interactome (BioPlex protein communities) capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q15006: EMC2
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Binary (HuRI) interactome captures of MMGT1 with multiple membrane proteins, many plausibly EMC clients. Bare protein binding is uninformative. Reason: High-throughput interactions partly reflecting client engagement; the bare term is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q9Y3D6: FIS1
GO:0005515 protein binding	IPI PMID:32439656 Structural basis for membrane insertion by the human ER memb...	KEEP AS NON CORE	Summary: Interaction evidence from the cryo-EM structural study of the human EMC, reflecting genuine intra-complex partnerships. Bare protein binding is uninformative. Reason: Real intra-complex interaction; the EMC complex membership term captures the informative content. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q9BV81: EMC6
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex affinity-MS interactome capture. Genuine partners but the bare term is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q15006: EMC2
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: OpenCell endogenous-tagging interactome capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q15006: EMC2
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	KEEP AS NON CORE	Summary: Solute carrier (SLC) superfamily interactome capture; many SLC partners are plausible EMC clients. Bare protein binding is uninformative. Reason: High-throughput interactions partly reflecting client engagement; the bare term is uninformative and not core. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Q8N4V1; Q969S0: SLC35B4
GO:0005737 cytoplasm	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Combined-IEA assignment of cytoplasm; MMGT1 is an integral ER membrane protein. Cytoplasm is an imprecise parent relative to the experimentally supported ER membrane localization. Reason: Generic and imprecise; the specific compartment is the ER membrane. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005769 early endosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara electronic transfer of early endosome localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Early endosome membrane
GO:0005794 Golgi apparatus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara electronic transfer of Golgi localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Golgi
GO:0005886 plasma membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara electronic transfer of plasma membrane localization; weakly supported and most likely reflecting transporter-family inference. Reason: Not supported experimentally for the human protein; inconsistent with the ER-membrane EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0015087 cobalt ion transmembrane transporter activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara transfer of a cobalt transporter activity from the rodent ortholog. No experimental support for cobalt transport by human MMGT1. Reason: Speculative metal-transporter activity from the contested family inference; superseded by the EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0015093 ferrous iron transmembrane transporter activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara transfer of a ferrous iron transporter activity from the rodent ortholog. No experimental support for iron transport by human MMGT1. Reason: Speculative metal-transporter activity; superseded by the EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0015095 magnesium ion transmembrane transporter activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara transfer of magnesium transporter activity from the rodent ortholog. UniProt records only a By-similarity possibility of Mg(2+) transport; the consensus role is as an EMC insertase subunit. Reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0022857 transmembrane transporter activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara transfer of generic transmembrane transporter activity from the rodent ortholog. Not the verified EMC insertase function. Reason: Derived from the contested transporter-family inference; superseded by the EMC role. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0000139 Golgi membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator ISS transfer of Golgi membrane localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Golgi
GO:0005789 endoplasmic reticulum membrane	EXP PMID:22119785 Defining human ERAD networks through an integrative mapping ...	ACCEPT	Summary: Experimental ER membrane localization from the EMC-discovery ERAD-network study. Core compartment. Reason: Experimentally supported core location. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0031901 early endosome membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator ISS transfer of early endosome membrane localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Early endosome membrane
GO:0005789 endoplasmic reticulum membrane	NAS PMID:29242231 The ER membrane protein complex is a transmembrane domain in...	ACCEPT	Summary: NAS annotation of ER membrane localization for the EMC from the insertase study, consistent with experimental evidence and the core compartment of MMGT1. Reason: Correct core location; consistent with EXP/IDA evidence. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence	IDA PMID:29242231 The ER membrane protein complex is a transmembrane domain in...	ACCEPT	Summary: The EMC inserts transmembrane domains, including stop-transfer membrane-anchor sequences of multipass proteins; MMGT1/EMC5 is part of the insertase. A core biological process of the EMC. Reason: Core EMC-mediated process; MMGT1 contributes as a constitutive subunit, and EMC5 depletion reduces client insertion. Supporting Evidence: PMID:29242231 The ER membrane protein complex is a transmembrane domain insertase
GO:0071816 tail-anchored membrane protein insertion into ER membrane	IDA PMID:29242231 The ER membrane protein complex is a transmembrane domain in...	ACCEPT	Summary: The EMC mediates post-translational insertion of tail-anchored proteins; demonstrated directly with the reconstituted complex. A core EMC process to which MMGT1 contributes as a subunit. Reason: Core EMC-mediated process; directly demonstrated. Supporting Evidence: PMID:29242231 The ER membrane protein complex is a transmembrane domain insertase
GO:0072546 EMC complex	IPI PMID:32439656 Structural basis for membrane insertion by the human ER memb...	ACCEPT	Summary: ComplexPortal/structural IPI assignment of EMC complex membership based on the cryo-EM structure of the human EMC. Core structural identity of MMGT1. Reason: Structurally demonstrated core EMC membership. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Component of the ER membrane protein complex (EMC).
GO:0032977 membrane insertase activity	IMP PMID:34918864 EMC is required for biogenesis of Xport-A, an essential chap...	KEEP AS NON CORE	Summary: In vivo Drosophila evidence that the EMC, including EMC5, is required for TMD membrane insertion of a tail-anchored client. MMGT1 is a small non-catalytic membrane subunit, so the insertase activity is a complex-level property to which it contributes. Reason: contributes_to is appropriate, but MMGT1 is not the catalytic insertase subunit (EMC3/EMC6 form the vestibule); the core MMGT1 identity is EMC membership and ER-membrane localization. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt energy-independent insertion into endoplasmic
GO:0071816 tail-anchored membrane protein insertion into ER membrane	IMP PMID:34918864 EMC is required for biogenesis of Xport-A, an essential chap...	ACCEPT	Summary: In vivo (Drosophila) IMP evidence that the EMC, including EMC5, is required for tail-anchored protein insertion. Core EMC process. Reason: Core EMC process; supported by in vivo loss-of-function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt post-translational insertion of tail-anchored/TA proteins in
GO:0032977 membrane insertase activity	IMP PMID:29809151 The ER membrane protein complex interacts cotranslationally ...	KEEP AS NON CORE	Summary: IMP evidence that EMC subunit depletion impairs membrane insertion; MMGT1 contributes to the complex-level insertase activity but is not the catalytic subunit. Reason: contributes_to is appropriate; complex-level catalysis by EMC3/EMC6, so not MMGT1's standalone core MF. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt energy-independent insertion into endoplasmic
GO:0032977 membrane insertase activity	IMP PMID:30415835 EMC Is Required to Initiate Accurate Membrane Protein Topoge...	KEEP AS NON CORE	Summary: IMP evidence (topogenesis study) supporting the EMC's membrane insertase activity, to which MMGT1 contributes as a subunit. Reason: contributes_to is appropriate; complex-level catalysis, not MMGT1's standalone core MF. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt energy-independent insertion into endoplasmic
GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence	IMP PMID:29809151 The ER membrane protein complex interacts cotranslationally ...	ACCEPT	Summary: The EMC is required for cotranslational insertion of multipass proteins in which stop-transfer membrane-anchor sequences become membrane-spanning helices; MMGT1 is part of the insertase. Core EMC process. Reason: Core EMC-mediated process; supported by IMP of EMC subunits. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning
GO:0005789 endoplasmic reticulum membrane	IDA PMID:32439656 Structural basis for membrane insertion by the human ER memb...	ACCEPT	Summary: Direct (structural) evidence placing MMGT1 in the ER membrane. Core compartment. Reason: Experimentally supported core location. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence	IMP PMID:30415835 EMC Is Required to Initiate Accurate Membrane Protein Topoge...	ACCEPT	Summary: IMP (topogenesis study) supporting the EMC's role in insertion of stop-transfer membrane-anchor sequences and N-exo topogenesis of multipass clients. Core EMC process. Reason: Core EMC-mediated process. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning
GO:0071816 tail-anchored membrane protein insertion into ER membrane	IMP PMID:29242231 The ER membrane protein complex is a transmembrane domain in...	ACCEPT	Summary: IMP evidence that the EMC is required for tail-anchored protein insertion into the ER membrane; MMGT1 is part of the insertase. Core EMC process. Reason: Core EMC-mediated process; directly demonstrated. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt post-translational insertion of tail-anchored/TA proteins in
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: High-throughput membrane-proteome detection (NK cell membrane proteome); a generic membrane localization, a parent of the specific ER membrane term. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0016020 membrane	IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ...	KEEP AS NON CORE	Summary: Direct generic membrane localization from the EMC-discovery study; a parent of the specific ER membrane term. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0072546 EMC complex	IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ...	ACCEPT	Summary: Direct experimental identification of MMGT1/EMC5 in the EMC by the foundational ERAD-network mapping study. Core structural identity. Reason: Core EMC membership; directly demonstrated. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Component of the ER membrane protein complex (EMC).
GO:0005769 early endosome	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator ISS transfer of early endosome localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Early endosome membrane
GO:0005794 Golgi apparatus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator ISS transfer of Golgi localization from the rodent ortholog. Reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt Golgi
GO:0015095 magnesium ion transmembrane transporter activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Curator ISS transfer of magnesium transporter activity from the rodent ortholog. UniProt records only a By-similarity possibility of Mg(2+) transport; the consensus role is as an EMC insertase subunit. Reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)
GO:0015693 magnesium ion transport	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Curator ISS transfer of a magnesium transport process from the rodent ortholog. Not demonstrated for the human protein. Reason: Speculative, By-similarity metal transport; superseded by the EMC insertase role and not a core function. Supporting Evidence: file:human/MMGT1/MMGT1-uniprot.txt May be involved in Mg(2+) transport (By similarity)

Core Functions

Constitutive small membrane subunit of the ER membrane protein complex (EMC), localizing to the ER membrane as part of the insertase that mediates energy-independent insertion of transmembrane domains.

Molecular Function:

membrane insertase activity

Cellular Locations:

endoplasmic reticulum membrane

In Complex:

EMC complex

Supporting Evidence:

file:human/MMGT1/MMGT1-uniprot.txt
Component of the ER membrane protein complex (EMC).
PMID:29242231
The ER membrane protein complex is a transmembrane domain insertase
PMID:38517390
Endogenous human EMC was purified via a Twin-Strep tag on EMC5, confirming EMC5/MMGT1 as a stable core membrane subunit of the complex.

As part of the EMC, contributes to post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins at the ER membrane.

Molecular Function:

membrane insertase activity

Directly Involved In:

tail-anchored membrane protein insertion into ER membrane protein insertion into ER membrane by stop-transfer membrane-anchor sequence

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

file:human/MMGT1/MMGT1-uniprot.txt
post-translational insertion of tail-anchored/TA proteins in
PMID:37957425
Thus, multipass membrane proteins can be released by the ribosome-translocon complex in an incompletely inserted state, requiring a separate EMC-mediated post-translational insertion step to rectify their topology, complete biogenesis and evade quality control.

References

PMID:32459176

The architecture of EMC reveals a path for membrane protein insertion.

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:22119785

Defining human ERAD networks through an integrative mapping strategy.

Affinity-MS ERAD-network mapping that first identified the EMC (including MMGT1/EMC5) in human cells and localized it to the ER membrane.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:29242231

The ER membrane protein complex is a transmembrane domain insertase.

EMC is a transmembrane domain insertase; depletion of EMC5/EMC6 reduces client insertion.

PMID:29809151

The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.

The EMC engages multipass membrane protein clients cotranslationally to enable their biogenesis.

PMID:30415835

EMC Is Required to Initiate Accurate Membrane Protein Topogenesis.

The EMC sets the N-exo topology of the first TMD of GPCRs and other multipass proteins.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32439656

Structural basis for membrane insertion by the human ER membrane protein complex.

Cryo-EM structure of the human EMC; defines MMGT1/EMC5 topology and intra-complex contacts.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34918864

EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel.

In vivo Drosophila evidence that the EMC, including EMC5, is required for TMD membrane insertion of a tail-anchored client.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:40355756

The solute carrier superfamily interactome.

PMID:37199759

A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.

The EMC hydrophilic vestibule acts as a charge-based selectivity filter that rejects mitochondrial tail-anchored proteins and enforces the positive-inside rule for multipass substrates; EMC5/MMGT1 is a core membrane subunit of this insertase/selectivity machine.

PMID:37196677

EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate.

Cryo-EM of an EMC-bound CaV1.2 assembly intermediate shows the EMC functions as a holdase/chaperone during multipass channel assembly, extending EMC function beyond insertion; EMC5 is a constitutive core subunit of this machine.

PMID:37957425

EMC rectifies the topology of multipass membrane proteins.

C-terminal TMDs of mammalian multipass proteins are inserted post-translationally by the EMC to rectify topology and complete biogenesis; this sequential co-/post-translational mechanism may apply to ~250 diverse multipass proteins. EMC5 is a core subunit of the EMC.

PMID:38517390

Structural insights into human EMC and its interaction with VDAC.

Cryo-EM structures of human EMC in apo and VDAC-bound states reveal a gating plug in the hydrophilic vestibule and an EMC-VDAC interaction at mitochondria-ER contact sites; endogenous human EMC was purified via a Twin-Strep tag on EMC5, showing EMC5 is a tractable handle for native EMC.

PMID:40753078

The EMC acts as a chaperone for membrane proteins.

Beyond TMD insertase activity, the EMC has a chaperone function engaging TMDs via its EMC1 subunit and modulating their orientation in the bilayer; productive TMD assembly reduces binding to the chaperone site. EMC5 is a core EMC subunit.

PMID:37269834

Identification of host regulators of Mycobacterium tuberculosis phenotypes uncovers a role for the MMGT1-GPR156 lipid droplet axis in persistence.

A genome-wide CRISPR screen prioritized MMGT1; MMGT1-deficient macrophages promote a switch of M. tuberculosis toward persistence, with upregulated lipid metabolism and lipid droplet accumulation driven by the orphan GPCR GPR156, and triacylglycerol-synthesis inhibition reduces both droplets and persistence.

Suggested Experiments

Experiment: Reconstitute purified EMC with and without EMC5 into proteoliposomes and assay both model TMD insertion and putative Mg2+ flux, to separate any intrinsic transport activity from the insertase function.

Experiment: Quantitative membrane proteomics of EMC5-knockout versus rescued cells to define the EMC5-dependent client repertoire and test whether magnesium homeostasis phenotypes are direct or secondary to impaired client biogenesis.

Deep Research

Falcon

(MMGT1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 33 citations 2 artifacts 2026-06-12T02:01:01.584203

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000016 I have extracted the requested figures and panels: - **Figure 1** (image-008) details the structural study of the VDAC1-bound EMC c (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of Human MMGT1 (UniProt Q8N4V1) / EMC5 / TMEM32

Executive summary

Human MMGT1 (Q8N4V1) is best supported as EMC5, a core integral-membrane subunit of the endoplasmic reticulum (ER) membrane protein complex (EMC) that participates in membrane protein biogenesis, rather than as a well-established standalone magnesium transporter. Multiple authoritative sources explicitly equate MMGT1 = EMC5 and place it in the ER-resident EMC complex. (rother2021signalpeptidasecomplex pages 1-2, chitwood2019theroleof pages 2-4)

Recent (2023–2024) structural and mechanistic work has substantially refined the current understanding of EMC function—including charge-based selectivity and topology enforcement (Pleiner 2023), post-translational insertion of C-terminal transmembrane domains (TMDs) to “rectify” multipass topology (Wu 2024), and high-resolution cryo-EM structures of human EMC (Li 2024). Although MMGT1’s historical name suggests Mg2+ transport, critical reviews conclude that direct functional evidence for MMgT/MMGT1 as a Mg2+ transporter remains limited, and alternative functions are plausible. (schaffers2018theriseand pages 1-2, chitwood2019theroleof pages 4-6)

Verification of gene/protein identity (critical disambiguation)

The target protein identity is consistent across the retrieved literature:

MMGT1 is explicitly equated with EMC5 in a Zika virus host-factor context (“MMGT1 = EMC5”), placing it within EMC. (Rother & Naumann, 2021; publication month April 2021; URL in citation) (rother2021signalpeptidasecomplex pages 1-2)
An authoritative EMC review enumerates EMC subunits and lists “EMC5 MMGT1 15 kDa”, indicating that MMGT1 is the canonical name used for EMC subunit 5 in humans. (Chitwood & Hegde, 2019; May 2019; https://doi.org/10.1016/j.tcb.2019.01.007) (chitwood2019theroleof pages 2-4)

No evidence in the retrieved corpus suggested a different human gene/protein being conflated with MMGT1 for UniProt Q8N4V1.

1) Key concepts and definitions (current understanding)

1.1 The ER membrane protein complex (EMC)

The EMC is an abundant, conserved, ER-resident multi-subunit complex involved in membrane protein biogenesis, including acting as a transmembrane-domain insertase and more broadly supporting client folding/assembly. (chitwood2019theroleof pages 1-2, chitwood2019theroleof pages 6-8)

A key conceptual framework is that EMC lowers barriers for insertion/topogenesis of challenging TMDs (e.g., lower hydrophobicity or problematic sequence features), complementing the Sec61 translocon and other insertases. (chitwood2019theroleof pages 6-8)

1.2 MMGT1/EMC5 as a “core” EMC subunit

Knockdown/knockout experiments in mammalian cells suggest that loss of EMC5 (MMGT1) strongly impairs integrity of remaining subunits, supporting that EMC5 is part of the core structural/functional scaffold of EMC. (chitwood2019theroleof pages 2-4)

1.3 Insertase vs “magnesium transporter” nomenclature

While MMGT1’s alternative name (“membrane magnesium transporter 1”) implies ion transport, critical review literature argues that for MMgT/MMGT1, functional evidence for Mg2+ transport is limited and that other functions have been suggested. (Schäffers et al., 2018; first published Feb 7 2018; https://doi.org/10.1152/ajprenal.00634.2017) (schaffers2018theriseand pages 1-2)

In parallel, EMC-focused literature notes that a reported Mg2+ transport phenotype upon EMC5 overexpression may be unrelated to EMC’s core insertase role. (chitwood2019theroleof pages 4-6)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 EMC selectivity filter enforces correct targeting and topology (2023)

Pleiner et al. (J Cell Biol, 2023; May 2023; https://doi.org/10.1083/jcb.202212007) describe a mechanistic selectivity filter at the EMC hydrophilic vestibule that uses charge repulsion to:

reduce misinsertion of mitochondrial tail-anchored proteins into the ER, and
enforce correct topology ("positive-inside" rule) for a subset of multipass substrates.

This work used mutagenesis, site-specific crosslinking, and split-GFP insertion reporters to track insertion outcomes and mechanistically connect EMC structure to client discrimination. (pleiner2023aselectivityfilter pages 1-2, pleiner2023aselectivityfilter pages 10-11)

Although this study focuses strongly on EMC3 residues controlling vestibule charge, the mechanistic implications apply to EMC as a whole and therefore contextualize EMC5 as a core membrane-subunit component of an insertase/selectivity machine. (pleiner2023aselectivityfilter pages 1-2)

2.2 EMC-mediated post-translational insertion “rectifies” multipass topology (2024 issue; published online 2023)

Wu et al. (Nature Structural & Molecular Biology; published online Nov 13, 2023; in January 2024 issue; https://doi.org/10.1038/s41594-023-01120-6) report that TMDs near the carboxyl terminus of mammalian multipass proteins can be inserted post-translationally by EMC, with site-specific crosslinking showing proximity of a pre-translocated C-terminal tail to EMC’s cytosol-facing hydrophilic vestibule.

Key quantitative statement: the authors propose that this sequential co-translational + post-translational mechanism may apply to ~250 diverse multipass proteins. (wu2024emcrectifiesthe pages 1-2)

This strengthens the view that EMC (and by extension EMC5/MMGT1 as a core subunit) is critical for topology completion and quality control evasion for a sizable membrane-protein subset. (wu2024emcrectifiesthe pages 1-2)

2.3 Structural biology of human EMC and EMC5-enabled purification (2024)

Li et al. (Aging (Albany NY), 2024; published Mar 15, 2024; https://doi.org/10.18632/aging.205660) report cryo-EM structures of human EMC in apo and VDAC-bound states at 3.47 Å and 3.32 Å, respectively. (li2024structuralinsightsinto pages 1-3)

Critically for MMGT1/EMC5 annotation and real-world implementation, Li et al. purified endogenous human EMC using a two-step affinity strategy with a 3×FLAG tag on EMC2 and a Twin-Strep tag on EMC5, followed by SEC, indicating EMC5 is an experimentally tractable handle for isolating native EMC. (li2024structuralinsightsinto pages 1-3)

The paper further emphasizes two transmembrane cavities—hydrophilic vestibule and lipid-filled hydrophobic groove—and identifies a gating plug segment (from EMC3) in the vestibule, supporting a regulatory mechanism for client insertion activity. (li2024structuralinsightsinto pages 1-3)

Visual evidence: EMC architecture and the EMC5-tag purification approach are depicted in Li et al.’s figure panels retrieved here. (li2024structuralinsightsinto media 7677c970, li2024structuralinsightsinto media 0611078d, li2024structuralinsightsinto media bf66669f, li2024structuralinsightsinto media 34b7fb19)

2.4 EMC as a chaperone/holdase for ion channel assembly (2023)

Chen et al. (Nature, 2023; published in final form July 2023; https://doi.org/10.1038/s41586-023-06175-5) provide cryo-EM structures of a large complex containing human CaV1.2–CaVβ3 bound to EMC, describing EMC “TM” and “Cyto” docks that remodel a client channel and facilitate handoff to CaVα2δ, supporting an EMC “holdase” role in channel biogenesis/assembly. (chen2023emcchaperone–cavstructure pages 1-3)

While this does not isolate EMC5’s unique biochemical action, it provides a high-authority example of EMC’s client-chaperone function consistent with the broad membrane-protein biogenesis framework in which EMC5 is a core membrane component. (chen2023emcchaperone–cavstructure pages 1-3, klose2025theemcacts pages 1-2)

3) Current applications and real-world implementations

3.1 EMC5 as an experimental handle for native EMC purification and structural biology

In practice, EMC5 tagging is used to obtain native EMC for cryo-EM: Li et al. explicitly used Twin-Strep–tagged EMC5 (with EMC2 3×FLAG) to purify endogenous EMC, enabling near-atomic resolution structure determination. (li2024structuralinsightsinto pages 1-3, li2024structuralinsightsinto media 7677c970)

This establishes a real-world implementation: EMC5 is a workable affinity handle for isolating intact EMC, useful for structural biology, interaction mapping, and reconstitution experiments.

3.2 EMC pathway as a mechanistic target to modulate membrane protein biogenesis

Mechanistic insights into EMC selectivity and topology control suggest potential applications in:

improving membrane protein expression/biogenesis in model systems, and
understanding pathogenic dependence on ER insertion/assembly pathways (e.g., viral multipass proteins).

These are applications of the EMC system rather than EMC5 alone, but EMC5’s “core” role implies it is a required component to manipulate EMC function. (pleiner2023aselectivityfilter pages 1-2, chitwood2019theroleof pages 2-4)

4) Expert opinions and analysis from authoritative sources

4.1 Authoritative synthesis: MMGT1/EMC5 is core to an insertase complex

Chitwood & Hegde (Trends Cell Biol, 2019) provide a high-authority synthesis that:

places EMC as a multi-subunit ER complex with multiple membrane subunits and a client insertion role, and
identifies EMC5/MMGT1 among core subunits whose knockdown disrupts complex integrity.

They also discuss that a reported Mg2+ transport phenotype linked to EMC5 overexpression could be unrelated to EMC’s core insertase function, reflecting caution in attributing magnesium transport as the primary function. (chitwood2019theroleof pages 4-6, chitwood2019theroleof pages 2-4)

4.2 Critical evaluation of Mg2+ transporter claims

Schäffers et al. (Am J Physiol Renal Physiol, 2018) emphasize that many proposed Mg2+ transporters were nominated by indirect evidence and that for MMgT/MMGT1, functional evidence is limited and additional characterization is needed before strong transporter claims. (schaffers2018theriseand pages 1-2)

5) Relevant statistics and data from recent studies

5.1 Structural data (2024)

Cryo-EM resolution: apo human EMC 3.47 Å; VDAC-bound EMC 3.32 Å. (Li et al., published Mar 15 2024) (li2024structuralinsightsinto pages 1-3)
Purification: endogenous EMC purified from Expi293F cells using 3×FLAG-EMC2 and Twin-Strep-EMC5. (li2024structuralinsightsinto pages 1-3)

5.2 Scope estimate of EMC-dependent topology rectification

Wu et al. estimate the sequential insertion mechanism may apply to ~250 multipass proteins. (published online Nov 13 2023; NSMB 2024 issue) (wu2024emcrectifiesthe pages 1-2)

5.3 Host-pathogen data: MMGT1 in macrophage control of M. tuberculosis persistence (2023)

Kalam et al. (Cell Host & Microbe, June 2023; https://doi.org/10.1016/j.chom.2023.05.009) provide quantitative experimental parameters and outcomes tying MMGT1 to infection phenotypes:

Infection model: THP-1 macrophages infected with TR-Mtb at MOI 0.5:1 (4 h inoculation) and sorted at 96 h. (kalam2023identificationofhost pages 25-30)
Distribution of phenotypic subsets among infected cells: ~46% AR and ~4% SNR (of the RFP+ infected population). (kalam2023identificationofhost pages 25-30)
Statistical reporting: validation experiments used two sgRNAs per gene, 3 independent experiments, mean ± SD; volcano plot cutoffs p<0.05; unpaired t-tests with significance annotated (★★ p<0.01, ★★★ p<0.001). (kalam2023identificationofhost pages 25-30)
Lipid droplet readouts: Lipidspot 488 staining with confocal imaging and FACS at 96 h post-infection. (kalam2023identificationofhost pages 25-30, kalam2023identificationofhost pages 30-35)
Perturbations: INH condition 1 µg/ml (2×MIC) for 24 h before plating; nevanimibe (ATR101) 100 nM and DGAT2 inhibitor 100 nM. (kalam2023identificationofhost pages 30-35)

These results provide strong evidence that MMGT1 impacts macrophage lipid droplet biology during infection; however, the mechanistic link to EMC insertase function vs Mg2+ transport is not resolved by the excerpts retrieved here. (kalam2023identificationofhost pages 25-30, kalam2023identificationofhost pages 30-35)

Evidence synthesis: primary molecular function and localization of MMGT1 (Q8N4V1)

Primary supported function

Across authoritative synthesis and recent mechanistic literature, the primary supported molecular role of MMGT1 is as EMC5, a structural component of EMC, which acts as an ER membrane insertase/chaperone for specific membrane proteins (tail-anchored and multipass client TMDs) and supports correct topogenesis. (chitwood2019theroleof pages 4-6, chitwood2019theroleof pages 6-8, pleiner2023aselectivityfilter pages 1-2, wu2024emcrectifiesthe pages 1-2)

Substrate specificity (what is “transported” or handled)

The most direct “substrate” concept supported here is transmembrane helices/domains of client proteins (including low-hydrophobicity TA proteins; and terminal TMDs of multipass proteins requiring topology completion). (pleiner2023aselectivityfilter pages 1-2, wu2024emcrectifiesthe pages 1-2, chitwood2019theroleof pages 6-8)

By contrast, Mg2+ as a transported substrate remains insufficiently supported by high-confidence functional assays in the retrieved evidence; multiple expert reviews advise caution. (schaffers2018theriseand pages 1-2, chitwood2019theroleof pages 4-6)

Cellular compartment and topology

MMGT1/EMC5 localizes to the ER membrane as an integral membrane subunit of EMC. (rother2021signalpeptidasecomplex pages 1-2, chitwood2019theroleof pages 2-4, li2024structuralinsightsinto pages 1-3)

Structural work on human EMC indicates a tripartite organization (luminal/membrane/cytosolic modules) and transmembrane cavities relevant to insertion, with EMC5 being used in purification and mapped within the membrane module in structural figures. (li2024structuralinsightsinto pages 1-3, li2024structuralinsightsinto media 7677c970)

Disease/pathophysiology and pathway contexts (supported by retrieved sources)

Viral infection/host factors: Host-factor studies identify EMC subunits (including MMGT1=EMC5) as relevant to viruses that require ER biogenesis of multipass viral proteins (e.g., Zika/DENV contexts described). (rother2021signalpeptidasecomplex pages 1-2, chitwood2019theroleof pages 2-4)
Host-pathogen lipid droplet axis in TB: MMGT1 deficiency in macrophages promotes M. tuberculosis persistence and lipid droplet accumulation, and pharmacologic targeting of TAG synthesis reduces droplet formation and persistence in this model. (kalam2023identificationofhost pages 1-3, kalam2023identificationofhost pages 25-30, kalam2023identificationofhost pages 30-35)

Summary table of functional annotation

Claim/Concept	Current understanding (1-2 sentences)	Key evidence/assay type	Key sources (include year, journal)	URL
Identity / synonyms	Human MMGT1 (UniProt Q8N4V1) is the same protein widely referred to in the literature as EMC5 and also as TMEM32. Reviews and primary papers explicitly identify EMC5/MMGT1 as a small (~15 kDa) subunit of the ER membrane protein complex (EMC), not a separate unrelated protein. (rother2021signalpeptidasecomplex pages 1-2, chitwood2019theroleof pages 2-4)	Complex annotation, purification/proteomics, review synthesis of EMC subunits	Chitwood & Hegde, 2019, Trends in Cell Biology; Rother & Naumann, 2021, Virus Research	https://doi.org/10.1016/j.tcb.2019.01.007 ; https://doi.org/10.1016/j.virusres.2021.198338
Localization: ER membrane; EMC complex	MMGT1/EMC5 is an integral ER membrane protein and one of the membrane-embedded EMC subunits. Mammalian EMC is an abundant ER-resident multi-subunit complex whose membrane subunits collectively form the transmembrane region involved in client handling. (rother2021signalpeptidasecomplex pages 1-2, binnian2023translationaltuningpreemptively pages 27-31, chitwood2019theroleof pages 2-4)	Subcellular complex purification, topology prediction, cryo-EM structural mapping	Chitwood & Hegde, 2019, Trends in Cell Biology; Li et al., 2024, Aging (Albany NY)	https://doi.org/10.1016/j.tcb.2019.01.007 ; https://doi.org/10.18632/aging.205660
Role in EMC stability	EMC5 is considered a core EMC subunit: individual depletion/knockout of EMC5 strongly disrupts integrity of the remaining complex, and CRISPR knockout can cause near-complete loss of other EMC subunits. This indicates MMGT1/EMC5 is structurally required for stable EMC assembly rather than being a peripheral accessory factor. (chitwood2019theroleof pages 2-4, chitwood2019theroleof pages 4-6)	Knockdown/CRISPR knockout with assessment of other subunits and complex integrity	Chitwood & Hegde, 2019, Trends in Cell Biology	https://doi.org/10.1016/j.tcb.2019.01.007
Role in membrane protein insertion / topogenesis	The strongest current functional assignment for MMGT1 is as part of EMC, a membrane-protein insertase/chaperone system that mediates insertion or topogenesis of low-hydrophobicity tail-anchored proteins and selected transmembrane domains of multipass proteins. EMC loss causes reduced client maturation, ER retention, topology defects, and altered expression of multipass membrane proteins; these phenotypes are attributed to the EMC machinery in which EMC5 is a core membrane subunit. (chitwood2019theroleof pages 4-6, chitwood2019theroleof pages 6-8, pleiner2023aselectivityfilter pages 1-2, wu2024emcrectifiesthe pages 1-2)	In vitro liposome reconstitution, cell-free microsome assays, split-GFP insertion assays, crosslinking, client maturation/localization phenotypes	Chitwood & Hegde, 2019, Trends in Cell Biology; Pleiner et al., 2023, Journal of Cell Biology; Wu et al., 2024, Nature Structural & Molecular Biology	https://doi.org/10.1016/j.tcb.2019.01.007 ; https://doi.org/10.1083/jcb.202212007 ; https://doi.org/10.1038/s41594-023-01120-6
Structural features: hydrophilic vestibule; relation to EMC3/6 cavity; tagging/purification via EMC5	Structural studies place EMC5 in the membrane module of EMC, contributing with EMC1/3/6 to a membrane cavity or lipid-filled region adjacent to the hydrophilic vestibule used for client insertion/topology control. Human EMC has also been purified through tagged EMC5 (for example, Twin-Strep/FLAG strategies), showing EMC5 is experimentally tractable as a stable core handle for native EMC purification. (klose2025theemcacts pages 1-2, li2024structuralinsightsinto pages 1-3, li2024structuralinsightsinto media 7677c970)	Cryo-EM, native complex purification, tagged endogenous EMC5 purification schemes	Li et al., 2024, Aging (Albany NY); Klose et al., 2025, Nature Communications	https://doi.org/10.18632/aging.205660 ; https://doi.org/10.1038/s41467-025-62109-x
Relation to viral infection	MMGT1/EMC5 has been recovered in host-factor studies as part of the EMC dependency of flaviviruses and other viruses that require ER biogenesis of viral multi-pass membrane proteins. The evidence supports an indirect role via EMC-mediated membrane protein biogenesis, not a virus-specific activity intrinsic to EMC5 alone. (rother2021signalpeptidasecomplex pages 1-2, chitwood2019theroleof pages 2-4)	CRISPR or RNAi host-factor screens; infection phenotypes linked to EMC disruption	Rother & Naumann, 2021, Virus Research; Chitwood & Hegde, 2019, Trends in Cell Biology	https://doi.org/10.1016/j.virusres.2021.198338 ; https://doi.org/10.1016/j.tcb.2019.01.007
Relation to Mycobacterium tuberculosis persistence and lipid droplets	A 2023 CRISPR-screen study prioritized MMGT1 for follow-up and found that MMGT1-deficient macrophages promoted an M. tuberculosis switch toward persistence, with upregulation of lipid metabolism genes and increased lipid droplets; triacylglycerol synthesis inhibition reduced both droplet formation and persistence. This is a real host-pathogen phenotype linked to MMGT1, but the study does not by itself prove whether the underlying mechanism is magnesium transport, EMC function, or another MMGT1-dependent pathway. (kalam2023identificationofhost pages 1-3, kalam2023identificationofhost pages 25-30)	Genome-wide CRISPR screen, CFU time courses, RNA-seq/GSEA, qPCR, confocal imaging, FACS lipid-droplet quantification	Kalam et al., 2023, Cell Host & Microbe	https://doi.org/10.1016/j.chom.2023.05.009
Magnesium transport evidence and caveats	MMGT1 was originally named a membrane magnesium transporter, but current evidence is mixed and weaker than the EMC evidence. Authoritative review literature explicitly states that for MMgT/MMGT1, functional evidence for bona fide Mg2+ transport is limited and alternative functions have been suggested; EMC-focused reviews note that reported Mg2+ transport upon overexpression may be unrelated to EMC’s core biogenesis role. (chitwood2019theroleof pages 4-6, schaffers2018theriseand pages 1-2)	Critical review of transporter literature; comparison of direct transport evidence versus alternative cell-biological roles	Schäffers et al., 2018, American Journal of Physiology-Renal Physiology; Chitwood & Hegde, 2019, Trends in Cell Biology	https://doi.org/10.1152/ajprenal.00634.2017 ; https://doi.org/10.1016/j.tcb.2019.01.007

Table: This table summarizes the best-supported functional annotation for human MMGT1/EMC5/TMEM32, emphasizing evidence that it is a core ER membrane subunit of the EMC complex involved in membrane protein biogenesis. It also highlights newer disease/infection-related findings and the important caveat that direct magnesium-transport evidence remains limited.

Limitations of this report (evidence gaps)

The retrieved evidence base strongly supports EMC5/EMC biology, but contains limited direct MMGT1-specific biochemical evidence distinguishing whether MMGT1 has an independent Mg2+ transport role in vivo. The most authoritative sources explicitly caution that Mg2+ transport evidence for MMgT/MMGT1 is limited. (schaffers2018theriseand pages 1-2, chitwood2019theroleof pages 4-6)
Several mechanistic papers define EMC’s insertase/chaperone mechanism without isolating EMC5’s unique residues or standalone activity; thus, EMC5 is annotated primarily as a core structural/functional component rather than a catalytically independent enzyme/transporter based on the current retrieved corpus. (pleiner2023aselectivityfilter pages 1-2, wu2024emcrectifiesthe pages 1-2, li2024structuralinsightsinto pages 1-3)

References

(rother2021signalpeptidasecomplex pages 1-2): Marion Rother and Michael Naumann. Signal peptidase complex subunit 1 is an essential zika virus host factor in placental trophoblasts. Apr 2021. URL: https://doi.org/10.1016/j.virusres.2021.198338, doi:10.1016/j.virusres.2021.198338. This article has 4 citations and is from a peer-reviewed journal.
(chitwood2019theroleof pages 2-4): Patrick J. Chitwood and Ramanujan S. Hegde. The role of emc during membrane protein biogenesis. Trends in cell biology, 29 5:371-384, May 2019. URL: https://doi.org/10.1016/j.tcb.2019.01.007, doi:10.1016/j.tcb.2019.01.007. This article has 97 citations and is from a domain leading peer-reviewed journal.
(schaffers2018theriseand pages 1-2): Olivier J. M. Schäffers, Joost G. J. Hoenderop, René J. M. Bindels, and Jeroen H. F. de Baaij. The rise and fall of novel renal magnesium transporters. American journal of physiology. Renal physiology, 314 6:F1027-F1033, Jun 2018. URL: https://doi.org/10.1152/ajprenal.00634.2017, doi:10.1152/ajprenal.00634.2017. This article has 66 citations.
(chitwood2019theroleof pages 4-6): Patrick J. Chitwood and Ramanujan S. Hegde. The role of emc during membrane protein biogenesis. Trends in cell biology, 29 5:371-384, May 2019. URL: https://doi.org/10.1016/j.tcb.2019.01.007, doi:10.1016/j.tcb.2019.01.007. This article has 97 citations and is from a domain leading peer-reviewed journal.
(chitwood2019theroleof pages 1-2): Patrick J. Chitwood and Ramanujan S. Hegde. The role of emc during membrane protein biogenesis. Trends in cell biology, 29 5:371-384, May 2019. URL: https://doi.org/10.1016/j.tcb.2019.01.007, doi:10.1016/j.tcb.2019.01.007. This article has 97 citations and is from a domain leading peer-reviewed journal.
(chitwood2019theroleof pages 6-8): Patrick J. Chitwood and Ramanujan S. Hegde. The role of emc during membrane protein biogenesis. Trends in cell biology, 29 5:371-384, May 2019. URL: https://doi.org/10.1016/j.tcb.2019.01.007, doi:10.1016/j.tcb.2019.01.007. This article has 97 citations and is from a domain leading peer-reviewed journal.
(pleiner2023aselectivityfilter pages 1-2): Tino Pleiner, Masami Hazu, Giovani Pinton Tomaleri, Vy N. Nguyen, Kurt Januszyk, and Rebecca M. Voorhees. A selectivity filter in the er membrane protein complex limits protein misinsertion at the er. The Journal of Cell Biology, May 2023. URL: https://doi.org/10.1083/jcb.202212007, doi:10.1083/jcb.202212007. This article has 28 citations.
(pleiner2023aselectivityfilter pages 10-11): Tino Pleiner, Masami Hazu, Giovani Pinton Tomaleri, Vy N. Nguyen, Kurt Januszyk, and Rebecca M. Voorhees. A selectivity filter in the er membrane protein complex limits protein misinsertion at the er. The Journal of Cell Biology, May 2023. URL: https://doi.org/10.1083/jcb.202212007, doi:10.1083/jcb.202212007. This article has 28 citations.
(wu2024emcrectifiesthe pages 1-2): Haoxi Wu, Luka Smalinskaitė, and Ramanujan S. Hegde. Emc rectifies the topology of multipass membrane proteins. Nature Structural & Molecular Biology, 31:32-41, Nov 2024. URL: https://doi.org/10.1038/s41594-023-01120-6, doi:10.1038/s41594-023-01120-6. This article has 41 citations and is from a highest quality peer-reviewed journal.
(li2024structuralinsightsinto pages 1-3): Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, and Ming Lei. Structural insights into human emc and its interaction with vdac. Aging (Albany NY), 16:5501-5525, Mar 2024. URL: https://doi.org/10.18632/aging.205660, doi:10.18632/aging.205660. This article has 6 citations.
(li2024structuralinsightsinto media 7677c970): Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, and Ming Lei. Structural insights into human emc and its interaction with vdac. Aging (Albany NY), 16:5501-5525, Mar 2024. URL: https://doi.org/10.18632/aging.205660, doi:10.18632/aging.205660. This article has 6 citations.
(li2024structuralinsightsinto media 0611078d): Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, and Ming Lei. Structural insights into human emc and its interaction with vdac. Aging (Albany NY), 16:5501-5525, Mar 2024. URL: https://doi.org/10.18632/aging.205660, doi:10.18632/aging.205660. This article has 6 citations.
(li2024structuralinsightsinto media bf66669f): Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, and Ming Lei. Structural insights into human emc and its interaction with vdac. Aging (Albany NY), 16:5501-5525, Mar 2024. URL: https://doi.org/10.18632/aging.205660, doi:10.18632/aging.205660. This article has 6 citations.
(li2024structuralinsightsinto media 34b7fb19): Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, and Ming Lei. Structural insights into human emc and its interaction with vdac. Aging (Albany NY), 16:5501-5525, Mar 2024. URL: https://doi.org/10.18632/aging.205660, doi:10.18632/aging.205660. This article has 6 citations.
(chen2023emcchaperone–cavstructure pages 1-3): Zhou Chen, Abhisek Mondal, Fayal Abderemane-Ali, Seil Jang, Sangeeta Niranjan, José L. Montaño, Balyn W. Zaro, and Daniel L. Minor. Emc chaperone–cav structure reveals an ion channel assembly intermediate. Nature, 619:410-419, May 2023. URL: https://doi.org/10.1038/s41586-023-06175-5, doi:10.1038/s41586-023-06175-5. This article has 77 citations and is from a highest quality peer-reviewed journal.
(klose2025theemcacts pages 1-2): Carolin J Klose, Kevin M Meighen-Berger, M. Kulke, Marina Parr, Barbara Steigenberger, Martin Zacharias, Dmitrij Frishman, and Matthias Feige. The emc acts as a chaperone for membrane proteins. Nature Communications, Aug 2025. URL: https://doi.org/10.1038/s41467-025-62109-x, doi:10.1038/s41467-025-62109-x. This article has 6 citations and is from a highest quality peer-reviewed journal.
(kalam2023identificationofhost pages 25-30): Haroon Kalam, Chih-Hung Chou, Motohiko Kadoki, Daniel B. Graham, Jacques Deguine, Deborah T. Hung, and Ramnik J. Xavier. Identification of host regulators of mycobacterium tuberculosis phenotypes uncovers a role for the mmgt1-gpr156 lipid droplet axis in persistence. Cell Host & Microbe, 31:978-992.e5, Jun 2023. URL: https://doi.org/10.1016/j.chom.2023.05.009, doi:10.1016/j.chom.2023.05.009. This article has 6 citations and is from a highest quality peer-reviewed journal.
(kalam2023identificationofhost pages 30-35): Haroon Kalam, Chih-Hung Chou, Motohiko Kadoki, Daniel B. Graham, Jacques Deguine, Deborah T. Hung, and Ramnik J. Xavier. Identification of host regulators of mycobacterium tuberculosis phenotypes uncovers a role for the mmgt1-gpr156 lipid droplet axis in persistence. Cell Host & Microbe, 31:978-992.e5, Jun 2023. URL: https://doi.org/10.1016/j.chom.2023.05.009, doi:10.1016/j.chom.2023.05.009. This article has 6 citations and is from a highest quality peer-reviewed journal.
(kalam2023identificationofhost pages 1-3): Haroon Kalam, Chih-Hung Chou, Motohiko Kadoki, Daniel B. Graham, Jacques Deguine, Deborah T. Hung, and Ramnik J. Xavier. Identification of host regulators of mycobacterium tuberculosis phenotypes uncovers a role for the mmgt1-gpr156 lipid droplet axis in persistence. Cell Host & Microbe, 31:978-992.e5, Jun 2023. URL: https://doi.org/10.1016/j.chom.2023.05.009, doi:10.1016/j.chom.2023.05.009. This article has 6 citations and is from a highest quality peer-reviewed journal.
(binnian2023translationaltuningpreemptively pages 27-31): Translational tuning pre-emptively modulates protein folding and secretory pathway defects This article has 0 citations.

Artifacts

Edison artifact artifact-00

Citations

rother2021signalpeptidasecomplex pages 1-2
chitwood2019theroleof pages 2-4
chitwood2019theroleof pages 6-8
schaffers2018theriseand pages 1-2
chitwood2019theroleof pages 4-6
pleiner2023aselectivityfilter pages 1-2
wu2024emcrectifiesthe pages 1-2
li2024structuralinsightsinto pages 1-3
kalam2023identificationofhost pages 25-30
kalam2023identificationofhost pages 30-35
chitwood2019theroleof pages 1-2
pleiner2023aselectivityfilter pages 10-11
klose2025theemcacts pages 1-2
kalam2023identificationofhost pages 1-3
binnian2023translationaltuningpreemptively pages 27-31
https://doi.org/10.1016/j.tcb.2019.01.007
https://doi.org/10.1152/ajprenal.00634.2017
https://doi.org/10.1083/jcb.202212007
https://doi.org/10.1038/s41594-023-01120-6
https://doi.org/10.18632/aging.205660
https://doi.org/10.1038/s41586-023-06175-5
https://doi.org/10.1016/j.chom.2023.05.009
https://doi.org/10.1016/j.virusres.2021.198338
https://doi.org/10.1038/s41467-025-62109-x
https://doi.org/10.1016/j.virusres.2021.198338,
https://doi.org/10.1016/j.tcb.2019.01.007,
https://doi.org/10.1152/ajprenal.00634.2017,
https://doi.org/10.1083/jcb.202212007,
https://doi.org/10.1038/s41594-023-01120-6,
https://doi.org/10.18632/aging.205660,
https://doi.org/10.1038/s41586-023-06175-5,
https://doi.org/10.1038/s41467-025-62109-x,
https://doi.org/10.1016/j.chom.2023.05.009,

📚 Additional Documentation

Notes

(MMGT1-notes.md)

MMGT1 (EMC5) review notes

UniProt: Q8N4V1 (EMC5_HUMAN). 131 aa, 2-TM (TM 4-22, 44-63), N-cyt/C-cyt topology with a small lumenal loop. Gene on chromosome X. HGNC symbol MMGT1; established alias EMC5; legacy alias TMEM32.

Core identity: EMC5, a small membrane subunit of the ER membrane protein complex (EMC)

UniProt RecName is now "ER membrane protein complex subunit 5", with EMC5 cited from the insertase paper PMID:29242231. The MMGT1 / "membrane magnesium transporter 1" / TMEM32 names are legacy HGNC names.
EMC is a ~9-10 subunit ER membrane insertase. The catalytic insertase core is EMC3 (YidC/Get1-like) plus EMC6; EMC5/MMGT1 is one of the small membrane subunits, not the catalytic subunit. EMC5 packs against EMC3/EMC6 in the cryo-EM structures (PDB 6WW7, 6Z3W, etc.).
Function (UniProt): "Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins" [file:human/MMGT1/MMGT1-uniprot.txt].
EMC inserts tail-anchored (TA) proteins of moderate/low hydrophobicity post-translationally, and cotranslationally inserts the first TMD (signal-anchor) of multipass proteins such as GPCRs, controlling N-exo topology.

Experimental basis (EMC role)

[PMID:22119785 Christianson et al. 2011] identified MMGT1/EMC5 as a component of the EMC during ERAD network mapping; basis for EMC complex membership (IDA, GO:0072546) and ER membrane localization (EXP, GO:0005789).
[PMID:29242231 Guna et al. 2018 "The ER membrane protein complex is a transmembrane domain insertase"] — directly implicates EMC5: "we initially noticed that SQS insertion was partially impaired when the EMC5 subunit of EMC was depleted with siRNAs"; "Ablation of EMC5 or EMC6 expression by gene editing ... reduced insertion of SQS". Establishes EMC as a TA-protein insertase, reconstituted with purified complex. Basis for GO:0071816, GO:0045050 IDA/IMP, and EMC membership NAS.
[PMID:29809151 Shurtleff et al. 2018] — EMC "binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters"; engages clients cotranslationally. Basis for GO:0045050 IMP and GO:0032977 membrane insertase activity (contributes_to) IMP.
[PMID:30415835 Chitwood et al. 2018] — EMC inserts the first TMD of GPCRs co-translationally, cooperating with Sec61 to set topology. Basis for GO:0045050 IMP and GO:0032977 contributes_to IMP.
[PMID:32439656 Pleiner et al. 2020] and PMID:32459176 O'Donnell et al. 2020 — cryo-EM structures of human EMC; defined EMC5 topology (TM helices, N-cyt/C-cyt). Basis for ER membrane IDA (GO:0005789) and EMC membership IPI (GO:0072546).
[PMID:34918864 Gaspar et al. 2022] — Drosophila EMC (incl. EMC5/EMC6) required for biogenesis of TA proteins fan and Xport-A; EMC5 depletion in testis renders flies infertile. FlyBase-assigned IMP for GO:0032977 (contributes_to) and GO:0071816. Although Drosophila-focused, this is a curator (FlyBase) experimental annotation; not removed.

Magnesium / metal-transporter annotations are legacy over-annotations

The "membrane magnesium transporter 1" name and the magnesium/cobalt/iron transmembrane-transporter GO annotations trace to the mouse ortholog (UniProtKB:Q8K273), originally from overexpression electrophysiology (Goytain & Quamme, who reported Mg2+ currents on overexpression of MMgT1/MMgT2). UniProt records only: "May be involved in Mg(2+) transport (By similarity)" [file:human/MMGT1/MMGT1-uniprot.txt] and SIMILARITY "Belongs to the membrane magnesium transporter (TC 1.A.67) family" [file:human/MMGT1/MMGT1-uniprot.txt].
In GOA, all the metal/transmembrane-transport annotations are electronic or ISS, propagated from Q8K273:
GO:0015095 magnesium ion transmembrane transporter activity — ISS (GO_REF:0000024) and IEA (GO_REF:0000107, from Q8K273).
GO:0015693 magnesium ion transport — ISS (GO_REF:0000024).
GO:1903830 magnesium ion transmembrane transport — IEA (GO_REF:0000108, inter-ontology link from GO:0015095).
GO:0015087 cobalt transporter activity / GO:0006824 cobalt ion transport — IEA from Q8K273 / inter-ontology.
GO:0015093 ferrous iron transporter activity / GO:0034755 iron ion transmembrane transport — IEA from Q8K273 / inter-ontology.
GO:0022857 transmembrane transporter activity (IBA, IEA) and GO:0055085 transmembrane transport (IEA) — generic, derived from the same transporter-family inference.
There is no direct experimental evidence that human EMC5 is a magnesium (or cobalt/iron) channel/transporter. The consensus role is as an EMC insertase subunit. The original overexpression electrophysiology has not been reproduced as a channel function, and the protein has no recognizable channel/transporter active site; the metal currents are most parsimoniously an overexpression artifact or indirect. These annotations are marked MARK_AS_OVER_ANNOTATED (the metal-transporter MF/BP terms) and the generic transmembrane-transporter terms KEEP_AS_NON_CORE / MARK_AS_OVER_ANNOTATED. Magnesium transport is NOT a core function.

Localization

ER membrane is the principal site (EXP PMID:22119785; IDA PMID:32439656; NAS PMID:29242231). UniProt SUBCELLULAR LOCATION: "Endoplasmic reticulum membrane".
Golgi apparatus membrane and early endosome membrane are ISS/IEA from the mouse ortholog Q8K273 (UniProt lists them as By similarity). Kept as non-core: plausible but the dominant, functionally relevant compartment is the ER. Plasma membrane (IBA/IEA) is weakly supported and likely reflects transporter-family phylogenetic inference; kept as non-core / over-annotated.

Protein binding (IPI) annotations

The numerous GO:0005515 IPI annotations (PMID:22119785, 26496610, 28514442, 32296183, 32439656, 33961781, 35271311, 40355756) come from high-throughput interactome / affinity studies. The cached texts do not name EMC5/MMGT1 specifically (large-scale screens). The most informative partners (EMC2 Q15006, EMC6 Q9BV81) reflect EMC complex assembly. Bare "protein binding" is uninformative per curation guidelines → KEEP_AS_NON_CORE; the EMC complex membership term (GO:0072546) captures the informative content.

Core functions (synthesis)

Structural subunit of the EMC (GO:0072546, part_of) in the ER membrane (GO:0005789).
As an EMC subunit, contributes to membrane protein insertion into the ER membrane: tail-anchored protein insertion (GO:0071816) and protein insertion by stop-transfer membrane-anchor sequence (GO:0045050), i.e. the EMC insertase activity (GO:0032977, contributes_to).

Magnesium transport: explicitly NOT a core function (legacy/contested).

Falcon deep-research findings (incorporated 2026-06)

New EMC5/MMGT1-relevant references verified against PubMed and added to the review (all additive; no action changes). Falcon confirms MMGT1 = EMC5 and that direct Mg2+-transport evidence remains weak/contested, consistent with the existing review.

2024 human EMC cryo-EM used a Twin-Strep tag on EMC5 (plus 3xFLAG-EMC2) to purify endogenous EMC, confirming EMC5/MMGT1 is a stable, tractable core membrane subunit; also reports an EMC-VDAC interaction at mitochondria-ER contact sites and a vestibule "gating plug." PMID:38517390
EMC post-translationally inserts C-terminal TMDs of multipass proteins to rectify topology, a sequential co-/post-translational mechanism estimated to apply to ~250 multipass proteins — expands the EMC client repertoire to which EMC5 contributes as a core subunit. PMID:37957425
EMC hydrophilic vestibule acts as a charge-based selectivity filter (rejects mitochondrial TA proteins; enforces positive-inside rule). PMID:37199759
EMC functions as a holdase/chaperone during assembly of the multipass CaV1.2 channel. PMID:37196677
A distinct EMC chaperone mode engages TMDs via EMC1 and modulates their bilayer orientation. PMID:40753078
MMGT1-specific host-pathogen finding: MMGT1-deficient macrophages promote M. tuberculosis persistence via a GPR156-driven lipid-droplet axis; TAG-synthesis inhibition reduces droplets and persistence. The paper does NOT resolve whether the mechanism is EMC function, Mg2+ transport, or another pathway, so it is recorded as informative context, not a core MF. PMID:37269834

Pn Notes

(MMGT1-pn-notes.md)

MMGT1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q8N4V1
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/MMGT1/MMGT1-ai-review.yaml
AIGR review HTML: missing - genes/human/MMGT1/MMGT1-ai-review.html
Gene notes: present - genes/human/MMGT1/MMGT1-notes.md
GOA TSV: present - genes/human/MMGT1/MMGT1-goa.tsv
UniProt record: present - genes/human/MMGT1/MMGT1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/MMGT1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/MMGT1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/MMGT1/MMGT1-deep-research-falcon.md

AIGR Review Snapshot

Description: MMGT1 (ER membrane protein complex subunit 5, EMC5; also known as membrane magnesium transporter 1 / TMEM32) is a small (131 aa) polytopic ER membrane protein with two transmembrane helices and cytoplasmic N- and C-termini. It is a constitutive subunit of the ER membrane protein complex (EMC), a conserved transmembrane-domain insertase and membrane-protein chaperone of the endoplasmic reticulum. Within the complex, EMC5 packs against the catalytic insertase subunits EMC3 and EMC6 that form the hydrophilic membrane vestibule through which substrate transmembrane domains are inserted. The EMC enables the energy-independent insertion of newly synthesized membrane proteins into the ER membrane, with a preference for transmembrane domains that are weakly hydrophobic or contain destabilizing charged or aromatic residues. It mediates post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins, including setting the N-exo topology of the first transmembrane domain of G protein-coupled receptors. MMGT1 localizes to the ER membrane and is broadly expressed. Its legacy designation as a membrane magnesium transporter derives from overexpression studies of the rodent ortholog and is not supported by a defined transport mechanism for the human protein.
Existing/core annotation action counts: ACCEPT: 13; KEEP_AS_NON_CORE: 24; MARK_AS_OVER_ANNOTATED: 14

PN Consistency Summary

Consistency: Mostly consistent, but MMGT1 is the gene where the legacy-name trap is live. Review, deep research, and PN annotation all treat MMGT1 as EMC5 (an EMC insertase subunit), and the review systematically MARK_AS_OVER_ANNOTATED the legacy metal-transport terms (GO:0015095 Mg, GO:0006824 Co, GO:0034755 Fe, GO:0022857, GO:0055085, GO:1903830, etc.) derived from rodent-ortholog By-similarity. GO:0072546 + ER membrane + insertion BPs captured. No contradiction with PN, which places it firmly as an EMC component.
PN story / NEW pressure: PN asserts only EMC-component/import role — no new pressure; fully captured by GO:0072546 and the insertion BPs. Conclusion: already captured.
Evidence alignment: Good overlap on EMC papers (PMID:22119785, PMID:29242231, PMID:38517390 — EMC5 used as Strep handle). Review adds the MMGT1-specific MtB persistence/lipid-droplet axis PMID:37269834 (mechanism unresolved, kept as context). PN cites no row-1 titles; no divergence.
Verdict: Consistent on EMC identity; legacy Mg/metal-transporter terms correctly over-annotated; PN adds no NEW pressure; note the misleading more_specific_than_existing_goa framing (compared against a rejected transport term).

Full Consistency Review

UniProt: Q8N4V1 (EMC5; legacy "membrane magnesium transporter 1" / TMEM32) · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE (very thorough; ~40 annotations including a large block of legacy transporter terms all adjudicated)
PN placement: ER proteostasis | Protein transport | Transmembrane protein import | EMC complex component; PN-node mapping: type=mapped/ok_for_propagation → GO:0072546 EMC complex (already_in_goa_exact); group→GO:0044743 (goa_status=more_specific_than_existing_goa); class→GO:0015031 (new_to_goa); branch=no_mapping.
Consistency: Mostly consistent, but MMGT1 is the gene where the legacy-name trap is live. Review, deep research, and PN annotation all treat MMGT1 as EMC5 (an EMC insertase subunit), and the review systematically MARK_AS_OVER_ANNOTATED the legacy metal-transport terms (GO:0015095 Mg, GO:0006824 Co, GO:0034755 Fe, GO:0022857, GO:0055085, GO:1903830, etc.) derived from rodent-ortholog By-similarity. GO:0072546 + ER membrane + insertion BPs captured. No contradiction with PN, which places it firmly as an EMC component.
PN story / NEW pressure: PN asserts only EMC-component/import role — no new pressure; fully captured by GO:0072546 and the insertion BPs. Conclusion: already captured.
Mapping strategy: Subtle. The dossier flags group→GO:0044743 as more_specific_than_existing_goa. MMGT1's existing GOA "transport" terms are GO:0055085 (transmembrane transport, IEA) and metal-transport terms — which the review is actively flagging as OVER-ANNOTATED (legacy magnesium-transporter artifact, not protein import). So the PN projection (GO:0044743 protein transmembrane import) is conceptually correct (insertion) but the more_specific_than_existing_goa comparison is being made against a transport term the review rejects, not against a genuine import annotation — the framing is misleading. type→GO:0072546 is exact/correct. Projected GO:0044743/GO:0015031 are broader than the review's specific insertion terms (broader-ancestor pattern, cf. TOMM20/HSPA8/RAB7A).
Evidence alignment: Good overlap on EMC papers (PMID:22119785, PMID:29242231, PMID:38517390 — EMC5 used as Strep handle). Review adds the MMGT1-specific MtB persistence/lipid-droplet axis PMID:37269834 (mechanism unresolved, kept as context). PN cites no row-1 titles; no divergence.
Verdict: Consistent on EMC identity; legacy Mg/metal-transporter terms correctly over-annotated; PN adds no NEW pressure; note the misleading more_specific_than_existing_goa framing (compared against a rejected transport term).

PN Dossier Context

review_batch: proteostasis-batch-2026-06-11
review_yaml: genes/human/MMGT1/MMGT1-ai-review.yaml
PN workbook rows: 1

PN row 1: ER proteostasis | Protein transport | Transmembrane protein import | EMC complex component

UniProt: Q8N4V1
In branches: ER
PN-node mapping records (path + ancestors):
- [type] ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0072546 EMC complex]
  rationale: This PN type denotes ER membrane protein complex components. The GO EMC complex cellular-component term is the direct target.
- [group] ER proteostasis|Protein transport|Transmembrane protein import
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0044743 protein transmembrane import into intracellular organelle]
  rationale: This PN group covers ER transmembrane-protein insertion/import systems such as EMC- and PAT-related pathways. The local GO cache does not expose an ER-specific matching term, so the broader intracellular-organelle transmembrane-import process is the best supported propagation target.
- [class] ER proteostasis|Protein transport
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
  rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
- [branch] ER proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (3)

GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport
GO:0044743 protein transmembrane import into intracellular organelle | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=ER proteostasis|Protein transport|Transmembrane protein import
GO:0072546 EMC complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q8N4V1
gene_symbol: MMGT1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: MMGT1 (ER membrane protein complex subunit 5, EMC5; also known as membrane magnesium transporter 1 / TMEM32) is a small (131 aa) polytopic ER membrane protein with two transmembrane helices and cytoplasmic N- and C-termini. It is a constitutive subunit of the ER membrane protein complex (EMC), a conserved transmembrane-domain insertase and membrane-protein chaperone of the endoplasmic reticulum. Within the complex, EMC5 packs against the catalytic insertase subunits EMC3 and EMC6 that form the hydrophilic membrane vestibule through which substrate transmembrane domains are inserted. The EMC enables the energy-independent insertion of newly synthesized membrane proteins into the ER membrane, with a preference for transmembrane domains that are weakly hydrophobic or contain destabilizing charged or aromatic residues. It mediates post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins, including setting the N-exo topology of the first transmembrane domain of G protein-coupled receptors. MMGT1 localizes to the ER membrane and is broadly expressed. Its legacy designation as a membrane magnesium transporter derives from overexpression studies of the rodent ortholog and is not supported by a defined transport mechanism for the human protein.
alternative_products:
- name: '1'
  id: Q8N4V1-1
- name: '2'
  id: Q8N4V1-2
  sequence_note: VSP_036488
existing_annotations:
- term:
    id: GO:0022857
    label: transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Generic transmembrane transporter activity propagated phylogenetically from the legacy "membrane magnesium transporter" family inference. The verified function of MMGT1 is as an EMC insertase subunit, not as a solute transporter.
    action: MARK_AS_OVER_ANNOTATED
    reason: No experimental evidence that human MMGT1 transports a solute; the transporter assignment derives from a legacy family name and is superseded by the EMC insertase role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic early-endosome localization, ultimately derived from the rodent ortholog. The experimentally verified compartment is the ER membrane.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization carried over by similarity but peripheral to the core ER-membrane EMC site of action.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Early endosome membrane
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic Golgi localization derived from the rodent ortholog. The core EMC site of action is the ER membrane.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity but peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Golgi
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic plasma-membrane localization, weakly supported and most likely reflecting the transporter-family inference. MMGT1 acts in the ER membrane as an EMC subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not supported by experimental evidence for the human protein; inconsistent with the ER-membrane EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0072546
    label: EMC complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: MMGT1/EMC5 is a constitutive subunit of the ER membrane protein complex; phylogenetic assignment is consistent with direct experimental and structural evidence. Core structural identity.
    action: ACCEPT
    reason: EMC complex membership is the core cellular-component identity of MMGT1; supported by IDA, cryo-EM structures, and the conserved EMC5 family.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Component of the ER membrane protein complex (EMC).
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of a Golgi membrane location from the UniProt subcellular location vocabulary, itself a By-similarity assignment from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the core ER-membrane EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Golgi
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for MMGT1.
    action: ACCEPT
    reason: Correct core location; redundant with experimental EXP/IDA evidence.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0006824
    label: cobalt ion transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Inter-ontology electronic inference of cobalt ion transport, derived ultimately from the legacy metal-transporter family assignment. No experimental support for cobalt transport by human MMGT1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative metal-transport process inferred from a contested family name; not the verified EMC insertase function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ARBA machine-learning assignment to the endomembrane system, a generic parent of the specific ER membrane localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of early endosome membrane localization from UniProt, a By-similarity assignment from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Early endosome membrane
- term:
    id: GO:0034755
    label: iron ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Inter-ontology electronic inference of iron transmembrane transport from the legacy metal-transporter family. No experimental support for iron transport by human MMGT1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative metal-transport process; not the verified EMC insertase function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0055085
    label: transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Generic transmembrane transport process inferred electronically from the transporter-activity assignment. Not the verified EMC insertase function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Derived from the contested transporter-family inference; superseded by the EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:1903830
    label: magnesium ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Inter-ontology electronic inference of magnesium transmembrane transport. UniProt records only a By-similarity possibility of Mg(2+) transport for human MMGT1; the consensus role is as an EMC insertase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22119785
  qualifier: enables
  review:
    summary: IntAct interactions from the foundational ERAD-network mapping study that first defined the EMC, including the EMC subunits EMC2 and EMC6. Genuine EMC partnership, but bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EMC partner interactions but the bare protein binding term is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q9BV81: EMC6'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Quantitative interactome (stoichiometry/abundance) capture; reflects EMC and membrane-protein partnerships. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q15006: EMC2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome (BioPlex protein communities) capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q15006: EMC2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary (HuRI) interactome captures of MMGT1 with multiple membrane proteins, many plausibly EMC clients. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactions partly reflecting client engagement; the bare term is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q9Y3D6: FIS1'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32439656
  qualifier: enables
  review:
    summary: Interaction evidence from the cryo-EM structural study of the human EMC, reflecting genuine intra-complex partnerships. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real intra-complex interaction; the EMC complex membership term captures the informative content.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q9BV81: EMC6'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-MS interactome capture. Genuine partners but the bare term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q15006: EMC2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q15006: EMC2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40355756
  qualifier: enables
  review:
    summary: Solute carrier (SLC) superfamily interactome capture; many SLC partners are plausible EMC clients. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactions partly reflecting client engagement; the bare term is uninformative and not core.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'Q8N4V1; Q969S0: SLC35B4'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Combined-IEA assignment of cytoplasm; MMGT1 is an integral ER membrane protein. Cytoplasm is an imprecise parent relative to the experimentally supported ER membrane localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic and imprecise; the specific compartment is the ER membrane.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl-Compara electronic transfer of early endosome localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Early endosome membrane
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl-Compara electronic transfer of Golgi localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Golgi
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl-Compara electronic transfer of plasma membrane localization; weakly supported and most likely reflecting transporter-family inference.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not supported experimentally for the human protein; inconsistent with the ER-membrane EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0015087
    label: cobalt ion transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl-Compara transfer of a cobalt transporter activity from the rodent ortholog. No experimental support for cobalt transport by human MMGT1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative metal-transporter activity from the contested family inference; superseded by the EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0015093
    label: ferrous iron transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl-Compara transfer of a ferrous iron transporter activity from the rodent ortholog. No experimental support for iron transport by human MMGT1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative metal-transporter activity; superseded by the EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0015095
    label: magnesium ion transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl-Compara transfer of magnesium transporter activity from the rodent ortholog. UniProt records only a By-similarity possibility of Mg(2+) transport; the consensus role is as an EMC insertase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0022857
    label: transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl-Compara transfer of generic transmembrane transporter activity from the rodent ortholog. Not the verified EMC insertase function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Derived from the contested transporter-family inference; superseded by the EMC role.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of Golgi membrane localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Golgi
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:22119785
  qualifier: located_in
  review:
    summary: Experimental ER membrane localization from the EMC-discovery ERAD-network study. Core compartment.
    action: ACCEPT
    reason: Experimentally supported core location.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of early endosome membrane localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Early endosome membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:29242231
  qualifier: located_in
  review:
    summary: NAS annotation of ER membrane localization for the EMC from the insertase study, consistent with experimental evidence and the core compartment of MMGT1.
    action: ACCEPT
    reason: Correct core location; consistent with EXP/IDA evidence.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0045050
    label: protein insertion into ER membrane by stop-transfer membrane-anchor sequence
  evidence_type: IDA
  original_reference_id: PMID:29242231
  qualifier: involved_in
  review:
    summary: The EMC inserts transmembrane domains, including stop-transfer membrane-anchor sequences of multipass proteins; MMGT1/EMC5 is part of the insertase. A core biological process of the EMC.
    action: ACCEPT
    reason: Core EMC-mediated process; MMGT1 contributes as a constitutive subunit, and EMC5 depletion reduces client insertion.
    supported_by:
    - reference_id: PMID:29242231
      supporting_text: The ER membrane protein complex is a transmembrane domain insertase
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IDA
  original_reference_id: PMID:29242231
  qualifier: involved_in
  review:
    summary: The EMC mediates post-translational insertion of tail-anchored proteins; demonstrated directly with the reconstituted complex. A core EMC process to which MMGT1 contributes as a subunit.
    action: ACCEPT
    reason: Core EMC-mediated process; directly demonstrated.
    supported_by:
    - reference_id: PMID:29242231
      supporting_text: The ER membrane protein complex is a transmembrane domain insertase
- term:
    id: GO:0072546
    label: EMC complex
  evidence_type: IPI
  original_reference_id: PMID:32439656
  qualifier: part_of
  review:
    summary: ComplexPortal/structural IPI assignment of EMC complex membership based on the cryo-EM structure of the human EMC. Core structural identity of MMGT1.
    action: ACCEPT
    reason: Structurally demonstrated core EMC membership.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Component of the ER membrane protein complex (EMC).
- term:
    id: GO:0032977
    label: membrane insertase activity
  evidence_type: IMP
  original_reference_id: PMID:34918864
  qualifier: contributes_to
  review:
    summary: In vivo Drosophila evidence that the EMC, including EMC5, is required for TMD membrane insertion of a tail-anchored client. MMGT1 is a small non-catalytic membrane subunit, so the insertase activity is a complex-level property to which it contributes.
    action: KEEP_AS_NON_CORE
    reason: contributes_to is appropriate, but MMGT1 is not the catalytic insertase subunit (EMC3/EMC6 form the vestibule); the core MMGT1 identity is EMC membership and ER-membrane localization.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: energy-independent insertion into endoplasmic
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IMP
  original_reference_id: PMID:34918864
  qualifier: involved_in
  review:
    summary: In vivo (Drosophila) IMP evidence that the EMC, including EMC5, is required for tail-anchored protein insertion. Core EMC process.
    action: ACCEPT
    reason: Core EMC process; supported by in vivo loss-of-function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: post-translational insertion of tail-anchored/TA proteins in
- term:
    id: GO:0032977
    label: membrane insertase activity
  evidence_type: IMP
  original_reference_id: PMID:29809151
  qualifier: contributes_to
  review:
    summary: IMP evidence that EMC subunit depletion impairs membrane insertion; MMGT1 contributes to the complex-level insertase activity but is not the catalytic subunit.
    action: KEEP_AS_NON_CORE
    reason: contributes_to is appropriate; complex-level catalysis by EMC3/EMC6, so not MMGT1's standalone core MF.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: energy-independent insertion into endoplasmic
- term:
    id: GO:0032977
    label: membrane insertase activity
  evidence_type: IMP
  original_reference_id: PMID:30415835
  qualifier: contributes_to
  review:
    summary: IMP evidence (topogenesis study) supporting the EMC's membrane insertase activity, to which MMGT1 contributes as a subunit.
    action: KEEP_AS_NON_CORE
    reason: contributes_to is appropriate; complex-level catalysis, not MMGT1's standalone core MF.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: energy-independent insertion into endoplasmic
- term:
    id: GO:0045050
    label: protein insertion into ER membrane by stop-transfer membrane-anchor sequence
  evidence_type: IMP
  original_reference_id: PMID:29809151
  qualifier: involved_in
  review:
    summary: The EMC is required for cotranslational insertion of multipass proteins in which stop-transfer membrane-anchor sequences become membrane-spanning helices; MMGT1 is part of the insertase. Core EMC process.
    action: ACCEPT
    reason: Core EMC-mediated process; supported by IMP of EMC subunits.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: stop-transfer membrane-anchor sequences become ER membrane spanning
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:32439656
  qualifier: located_in
  review:
    summary: Direct (structural) evidence placing MMGT1 in the ER membrane. Core compartment.
    action: ACCEPT
    reason: Experimentally supported core location.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0045050
    label: protein insertion into ER membrane by stop-transfer membrane-anchor sequence
  evidence_type: IMP
  original_reference_id: PMID:30415835
  qualifier: involved_in
  review:
    summary: IMP (topogenesis study) supporting the EMC's role in insertion of stop-transfer membrane-anchor sequences and N-exo topogenesis of multipass clients. Core EMC process.
    action: ACCEPT
    reason: Core EMC-mediated process.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: stop-transfer membrane-anchor sequences become ER membrane spanning
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IMP
  original_reference_id: PMID:29242231
  qualifier: involved_in
  review:
    summary: IMP evidence that the EMC is required for tail-anchored protein insertion into the ER membrane; MMGT1 is part of the insertase. Core EMC process.
    action: ACCEPT
    reason: Core EMC-mediated process; directly demonstrated.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: post-translational insertion of tail-anchored/TA proteins in
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome detection (NK cell membrane proteome); a generic membrane localization, a parent of the specific ER membrane term.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:22119785
  qualifier: located_in
  review:
    summary: Direct generic membrane localization from the EMC-discovery study; a parent of the specific ER membrane term.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0072546
    label: EMC complex
  evidence_type: IDA
  original_reference_id: PMID:22119785
  qualifier: part_of
  review:
    summary: Direct experimental identification of MMGT1/EMC5 in the EMC by the foundational ERAD-network mapping study. Core structural identity.
    action: ACCEPT
    reason: Core EMC membership; directly demonstrated.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Component of the ER membrane protein complex (EMC).
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of early endosome localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Early endosome membrane
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of Golgi localization from the rodent ortholog.
    action: KEEP_AS_NON_CORE
    reason: Possible minor localization by similarity; peripheral to the ER-membrane EMC core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: Golgi
- term:
    id: GO:0015095
    label: magnesium ion transmembrane transporter activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Curator ISS transfer of magnesium transporter activity from the rodent ortholog. UniProt records only a By-similarity possibility of Mg(2+) transport; the consensus role is as an EMC insertase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative, By-similarity metal transport not demonstrated for the human protein; not a core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
- term:
    id: GO:0015693
    label: magnesium ion transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Curator ISS transfer of a magnesium transport process from the rodent ortholog. Not demonstrated for the human protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Speculative, By-similarity metal transport; superseded by the EMC insertase role and not a core function.
    supported_by:
    - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
      supporting_text: May be involved in Mg(2+) transport (By similarity)
core_functions:
- description: Constitutive small membrane subunit of the ER membrane protein complex (EMC), localizing to the ER membrane as part of the insertase that mediates energy-independent insertion of transmembrane domains.
  molecular_function:
    id: GO:0032977
    label: membrane insertase activity
  in_complex:
    id: GO:0072546
    label: EMC complex
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
    supporting_text: Component of the ER membrane protein complex (EMC).
  - reference_id: PMID:29242231
    supporting_text: The ER membrane protein complex is a transmembrane domain insertase
  - reference_id: PMID:38517390
    supporting_text: Endogenous human EMC was purified via a Twin-Strep tag on EMC5, confirming EMC5/MMGT1 as a stable core membrane subunit of the complex.
    full_text_unavailable: true
- description: As part of the EMC, contributes to post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins at the ER membrane.
  molecular_function:
    id: GO:0032977
    label: membrane insertase activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/MMGT1/MMGT1-uniprot.txt
    supporting_text: post-translational insertion of tail-anchored/TA proteins in
  - reference_id: PMID:37957425
    supporting_text: >-
      Thus, multipass membrane proteins can be released by the ribosome-translocon complex in
      an incompletely inserted state, requiring a separate EMC-mediated post-translational
      insertion step to rectify their topology, complete biogenesis and evade quality control.
  directly_involved_in:
  - id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  - id: GO:0045050
    label: protein insertion into ER membrane by stop-transfer membrane-anchor sequence
proposed_new_terms: []
references:
- id: PMID:32459176
  title: The architecture of EMC reveals a path for membrane protein insertion.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'O''Donnell et al. 2020 (eLife). Cryo-EM architecture of the human EMC,
      establishing the overall complex organization and subunit topology relevant to
      MMGT1 as a constitutive EMC subunit.'
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput membrane proteome; source of a generic membrane localization.
- id: PMID:22119785
  title: Defining human ERAD networks through an integrative mapping strategy.
  findings:
  - statement: Affinity-MS ERAD-network mapping that first identified the EMC (including MMGT1/EMC5) in human cells and localized it to the ER membrane.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational identification of the human EMC; source of EMC membership and ER membrane localization for MMGT1.
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Quantitative interactome; source of an IPI protein-binding annotation.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex interactome; source of an IPI protein-binding annotation.
- id: PMID:29242231
  title: The ER membrane protein complex is a transmembrane domain insertase.
  findings:
  - statement: EMC is a transmembrane domain insertase; depletion of EMC5/EMC6 reduces client insertion.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the insertase function of the EMC; implicates EMC5 directly in insertion.
- id: PMID:29809151
  title: The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.
  findings:
  - statement: The EMC engages multipass membrane protein clients cotranslationally to enable their biogenesis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cotranslational multipass biogenesis role of the EMC.
- id: PMID:30415835
  title: EMC Is Required to Initiate Accurate Membrane Protein Topogenesis.
  findings:
  - statement: The EMC sets the N-exo topology of the first TMD of GPCRs and other multipass proteins.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Topogenesis/orientation role of the EMC.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HuRI binary interactome; source of IPI protein-binding partners.
- id: PMID:32439656
  title: Structural basis for membrane insertion by the human ER membrane protein complex.
  findings:
  - statement: Cryo-EM structure of the human EMC; defines MMGT1/EMC5 topology and intra-complex contacts.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis for the EMC; abstract-only in cache.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex affinity-MS interactome; source of an IPI protein-binding annotation.
- id: PMID:34918864
  title: EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel.
  findings:
  - statement: In vivo Drosophila evidence that the EMC, including EMC5, is required for TMD membrane insertion of a tail-anchored client.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: In vivo loss-of-function support for the EMC insertase function; basis for the FlyBase IMP annotations.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: OpenCell interactome/localization; source of an IPI protein-binding annotation.
- id: PMID:40355756
  title: The solute carrier superfamily interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: SLC interactome; SLC partners are plausible EMC clients; source of an IPI protein-binding annotation.
- id: PMID:37199759
  title: A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.
  findings:
  - statement: The EMC hydrophilic vestibule acts as a charge-based selectivity filter that rejects mitochondrial tail-anchored proteins and enforces the positive-inside rule for multipass substrates; EMC5/MMGT1 is a core membrane subunit of this insertase/selectivity machine.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (J Cell Biol 2023). Recent mechanistic refinement of the EMC insertase (selectivity filter/topology enforcement); contextualizes EMC5 as a core membrane component, though the tested charged residues are on EMC3.
- id: PMID:37196677
  title: "EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate."
  findings:
  - statement: Cryo-EM of an EMC-bound CaV1.2 assembly intermediate shows the EMC functions as a holdase/chaperone during multipass channel assembly, extending EMC function beyond insertion; EMC5 is a constitutive core subunit of this machine.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Nature 2023). High-authority example of the EMC holdase/chaperone mode for a multipass client; supports the complex-level functions to which EMC5 contributes.
- id: PMID:37957425
  title: EMC rectifies the topology of multipass membrane proteins.
  findings:
  - statement: C-terminal TMDs of mammalian multipass proteins are inserted post-translationally by the EMC to rectify topology and complete biogenesis; this sequential co-/post-translational mechanism may apply to ~250 diverse multipass proteins. EMC5 is a core subunit of the EMC.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Nat Struct Mol Biol 2023/2024). Expands the EMC client repertoire and topology-completion role; supports the stop-transfer/multipass insertion processes to which EMC5 contributes as a core subunit.
- id: PMID:38517390
  title: Structural insights into human EMC and its interaction with VDAC.
  findings:
  - statement: Cryo-EM structures of human EMC in apo and VDAC-bound states reveal a gating plug in the hydrophilic vestibule and an EMC-VDAC interaction at mitochondria-ER contact sites; endogenous human EMC was purified via a Twin-Strep tag on EMC5, showing EMC5 is a tractable handle for native EMC.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Aging 2024). Human EMC structure; EMC5 used as the affinity handle for native complex purification, confirming EMC5 as a stable core membrane subunit; also documents an EMC-VDAC interaction at MERCs.
- id: PMID:40753078
  title: The EMC acts as a chaperone for membrane proteins.
  findings:
  - statement: Beyond TMD insertase activity, the EMC has a chaperone function engaging TMDs via its EMC1 subunit and modulating their orientation in the bilayer; productive TMD assembly reduces binding to the chaperone site. EMC5 is a core EMC subunit.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Nat Commun 2025). Defines an additional EMC chaperone mode (client features, EMC1-mediated TMD engagement); supports the broader membrane-protein biogenesis role of the EMC of which EMC5 is a core member.
- id: PMID:37269834
  title: Identification of host regulators of Mycobacterium tuberculosis phenotypes uncovers a role for the MMGT1-GPR156 lipid droplet axis in persistence.
  findings:
  - statement: A genome-wide CRISPR screen prioritized MMGT1; MMGT1-deficient macrophages promote a switch of M. tuberculosis toward persistence, with upregulated lipid metabolism and lipid droplet accumulation driven by the orphan GPCR GPR156, and triacylglycerol-synthesis inhibition reduces both droplets and persistence.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Cell Host Microbe 2023). MMGT1-specific host-pathogen phenotype (lipid droplet/persistence axis); the study does not resolve whether the mechanism is via EMC function, magnesium transport, or another pathway, so recorded as informative context rather than a core molecular function.
suggested_questions:
- question: Does human MMGT1/EMC5 have any genuine magnesium (or other metal) transport activity in its physiological ER context, or is the reported metal transport an overexpression artifact unrelated to its EMC function?
- question: What is the specific structural contribution of EMC5 to stability and substrate gating of the EMC3/EMC6 insertase vestibule?
suggested_experiments:
- description: Reconstitute purified EMC with and without EMC5 into proteoliposomes and assay both model TMD insertion and putative Mg2+ flux, to separate any intrinsic transport activity from the insertase function.
- description: Quantitative membrane proteomics of EMC5-knockout versus rescued cells to define the EMC5-dependent client repertoire and test whether magnesium homeostasis phenotypes are direct or secondary to impaired client biogenesis.

MMGT1

Gene Description

Existing Annotations Review

Core Functions

Constitutive small membrane subunit of the ER membrane protein complex (EMC), localizing to the ER membrane as part of the insertase that mediates energy-independent insertion of transmembrane domains.

As part of the EMC, contributes to post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins at the ER membrane.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Functional Annotation of Human MMGT1 (UniProt Q8N4V1) / EMC5 / TMEM32

Executive summary

Verification of gene/protein identity (critical disambiguation)

1) Key concepts and definitions (current understanding)

1.1 The ER membrane protein complex (EMC)

1.2 MMGT1/EMC5 as a “core” EMC subunit

1.3 Insertase vs “magnesium transporter” nomenclature

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 EMC selectivity filter enforces correct targeting and topology (2023)

2.2 EMC-mediated post-translational insertion “rectifies” multipass topology (2024 issue; published online 2023)

2.3 Structural biology of human EMC and EMC5-enabled purification (2024)

2.4 EMC as a chaperone/holdase for ion channel assembly (2023)

3) Current applications and real-world implementations

3.1 EMC5 as an experimental handle for native EMC purification and structural biology

3.2 EMC pathway as a mechanistic target to modulate membrane protein biogenesis

4) Expert opinions and analysis from authoritative sources

4.1 Authoritative synthesis: MMGT1/EMC5 is core to an insertase complex

4.2 Critical evaluation of Mg2+ transporter claims

5) Relevant statistics and data from recent studies

5.1 Structural data (2024)

5.2 Scope estimate of EMC-dependent topology rectification

5.3 Host-pathogen data: MMGT1 in macrophage control of M. tuberculosis persistence (2023)

Evidence synthesis: primary molecular function and localization of MMGT1 (Q8N4V1)

Primary supported function

Substrate specificity (what is “transported” or handled)

Cellular compartment and topology

Disease/pathophysiology and pathway contexts (supported by retrieved sources)

Summary table of functional annotation

Limitations of this report (evidence gaps)

Artifacts

Citations

📚 Additional Documentation

Notes

MMGT1 (EMC5) review notes

Core identity: EMC5, a small membrane subunit of the ER membrane protein complex (EMC)

Experimental basis (EMC role)

Magnesium / metal-transporter annotations are legacy over-annotations

Localization

Protein binding (IPI) annotations

Core functions (synthesis)

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

MMGT1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: ER proteostasis | Protein transport | Transmembrane protein import | EMC complex component

Projected GO annotations (3)

Note

📄 View Raw YAML