InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MFN2

Summary

InnateDB Protein

IDBP-369397.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MFN2

Protein Name

mitofusin 2

Synonyms

CMT2A; CMT2A2; CPRP1; HSG; MARF;

Species

Homo sapiens

Ensembl Protein

ENSP00000416338

InnateDB Gene

IDBG-89999 (MFN2)

Protein Structure

UniProt Annotation

Function

Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN2 acts independently of the cytoskeleton. It therefore plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. Overexpression induces the formation of mitochondrial networks. Plays an important role in the regulation of vascular smooth muscle cell proliferation. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PARK2 recruitment to dysfunctional mitochondria. Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress. Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions. {ECO:0000269PubMed:11181170, ECO:0000269PubMed:11950885, ECO:0000269PubMed:15322553, ECO:0000269PubMed:23620051, ECO:0000269PubMed:23921378}.

Subcellular Localization

Mitochondrion outer membrane {ECO:0000269PubMed:11181170, ECO:0000269PubMed:11950885, ECO:0000269PubMed:12499352, ECO:0000269PubMed:23620051}; Multi- pass membrane protein {ECO:0000269PubMed:11181170, ECO:0000269PubMed:11950885, ECO:0000269PubMed:12499352, ECO:0000269PubMed:23620051}. Note=Colocalizes with BAX during apoptosis.

Disease Associations

Charcot-Marie-Tooth disease 2A2 (CMT2A2) [MIM:609260]: 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. Nerve conduction velocities are normal or slightly reduced. {ECO:0000269PubMed:15064763, ECO:0000269PubMed:15549395, ECO:0000269PubMed:22206013}. Note=The disease is caused by mutations affecting the gene represented in this entry.Charcot-Marie-Tooth disease 6 (CMT6) [MIM:601152]: A form of Charcot-Marie-Tooth disease characterized by the association of axonal peripheral neuropathy with optic atrophy. 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, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. {ECO:0000269PubMed:16437557}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous; expressed at low level. Highly expressed in heart and kidney. {ECO:0000269PubMed:11950885, ECO:0000269PubMed:12759376}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 17 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	17 [view]
Protein-Protein	17 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003924	GTPase activity
GO:0005515	protein binding
GO:0005525	GTP binding
GO:0031625	ubiquitin protein ligase binding

Biological Process

GO:0006184	GTP catabolic process
GO:0006626	protein targeting to mitochondrion
GO:0007006	mitochondrial membrane organization
GO:0007596	blood coagulation
GO:0008053	mitochondrial fusion
GO:0008219	cell death
GO:0045087	innate immune response (InnateDB)
GO:0046580	negative regulation of Ras protein signal transduction
GO:0048662	negative regulation of smooth muscle cell proliferation
GO:0051646	mitochondrion localization

Cellular Component

GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005829	cytosol
GO:0016021	integral component of membrane
GO:0031306	intrinsic to mitochondrial outer membrane