Recombinant Human Mitofusin-2 (MFN2) Protein

Function

Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity)

Subcellular Location

Mitochondrion outer membrane (Multi-pass membrane protein)

Disease Association

Charcot-Marie-Tooth disease, axonal, type 2A2B (CMT2A2B) : An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2A2B is a severe form with autosomal recessive inheritance. [The disease is caused by variants affecting the gene represented in this entry] | Charcot-Marie-Tooth disease, axonal, type 2A2A (CMT2A2A) : An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. [The disease is caused by variants affecting the gene represented in this entry] | Neuropathy, hereditary motor and sensory, 6A, with optic atrophy (HMSN6A) : An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities. [The disease is caused by variants affecting the gene represented in this entry] | Lipomatosis, multiple symmetric, with or without peripheral neuropathy (MSL) : An autosomal recessive disorder characterized by the growth of unencapsulated, lipomatous masses affecting the upper body, especially the cervical and thoracic regions. Lipomatosis can be disfiguring, and lipoma growth around the neck may cause difficulty swallowing or breathing. The age at onset ranges from childhood to young adulthood. Some patients develop distal muscle weakness and atrophy due to axonal peripheral neuropathy. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Ubiquitous; expressed at low level. Highly expressed in heart and kidney

Subunit

Forms homomultimers and heteromultimers with MFN1 (PubMed:26085578, PubMed:38843396). Oligomerization is essential for mitochondrion fusion (Probable). Interacts with VAT1 (By similarity). Interacts with STOML2; may form heterooligomers (PubMed:17121834). Interacts (phosphorylated) with PRKN (PubMed:23620051). Interacts with EIF2AK3 (By similarity). Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN2. Interacts with TRABD (PubMed:38843396)

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