Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Defining the membrane proteome of NK cells.
Proteomic characterization of the human sperm nucleus.
tBid undergoes multiple conformational changes at the membrane required for Bax activation.
A reference map of the human binary protein interactome.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
MTCH2 is a mitochondrial outer membrane protein insertase.
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Established MTCH2 as an insertase necessary and sufficient for insertion of alpha-helical mitochondrial outer membrane proteins, using genome-wide CRISPRi, in vitro insertion into mitochondria from knockout cells, and reconstitution of purified MTCH2 into proteoliposomes.
Definition of the human mitochondrial TOM interactome reveals TRABD as a new interacting protein.
The mammalian protein MTCH1 can function as an insertase.
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MTCH1, but not MTCH2, complements loss of the yeast Mim1/Mim2 complex. High-level MTCH2 expression is toxic in yeast and the protein is found mainly in the endoplasmic reticulum in mim1-delta cells; lowering expression improves viability but does not restore complementation.
MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes.
MTCH2 promotes BAX and BAK self-assembly and apoptotic pore growth.
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In situ proximity labelling places MTCH2 next to BAX and BAK assemblies specifically under apoptotic conditions; MTCH2 loss delays BAX and BAK oligomerisation and reduces apoptotic sensitivity, sublethal permeabilisation, mitochondrial DNA release and cGAS-STING activation.
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The effect is independent of insertase activity: it persists with the insertase-dead D189R mutant, MTCH1 (which has insertase activity) does not reproduce it, and exogenous lysophosphatidic acid rescues the assembly defect, implicating lipid metabolism.
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MTCH2 acts on BAX and BAK directly, in addition to its established role in recruiting tBID to mitochondria.
Structural evolution of the MTCH family of mitochondrial insertases.
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Cryo-EM structure of human MTCH2 shows five transmembrane helices rather than the canonical six of SLC25 carriers; the missing helix creates a lipid-accessible hydrophilic groove stabilised by a C-terminal domain unique to the MTCH family, and the residues lining the groove set the insertion rate.
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The MTCH family has lost transporter elements including the interhelical salt bridges required for alternating access; restoring those salt bridges does not reduce insertase activity.
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MTCH1 partially rescues loss of MTCH2 for several alpha-helical outer-membrane substrates in human cells, and the same groove architecture identifies a plant outer-membrane insertase.
Falcon deep research report for human MTCH2
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MTCH2 is an integral mitochondrial outer membrane protein whose most strongly supported primary function is insertion of alpha-helical outer membrane proteins.
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MTCH2 can facilitate BID/tBID-associated mitochondrial apoptosis, but this is best treated as non-core relative to the insertase function.
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Recent work links MTCH2 to mitochondrial fusion and lipid metabolism, including MFN2/LPA-associated fusion plasticity, as secondary or emerging functional contexts.