MMGT1

UniProt ID: Q8N4V1
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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 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evidence that human MMGT1 transports a solute; the transporter assignment derives from a legacy family name and is superseded by the EMC insertase role.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
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.

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

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Suggested Questions for Experts

Q: 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?

Q: What is the specific structural contribution of EMC5 to stability and substrate gating of the EMC3/EMC6 insertase vestibule?

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)

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πŸ“š Additional Documentation

Notes

(MMGT1-notes.md)

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Pn Notes

(MMGT1-pn-notes.md)

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πŸ“„ View Raw YAML

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