MFN1 mitofusin 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MFN1provided by HGNC
Official Full Name: mitofusin 1provided by HGNC
Primary source: HGNC:HGNC:18262
See related: Ensembl:ENSG00000171109 MIM:608506
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: hfzo1; hfzo2
Summary: The protein encoded by this gene is a mediator of mitochondrial fusion. This protein and mitofusin 2 are homologs of the Drosophila protein fuzzy onion (Fzo). They are mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in heart (RPKM 9.7), prostate (RPKM 9.7) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 3q26.33

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	3	NC_000003.12 (179347709..179394936)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (179065480..179111014)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

heptad repeat domain of Mitofusin proteins induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface.
Title: The heptad repeat domain 1 of Mitofusin has membrane destabilization function in mitochondrial fusion.
The mRNA upregulation of Mitofusin 1 and 2 provides first insight into the complex changes of mitochondrial dynamics in cardiomyocytes of patients with reversible heart failure due to tachycardiomyopathy.
Title: Mitochondrial Dynamics in Tachycardiomyopathy.
The results lead to a revised understanding of Mfn 1 as single-spanning outer membrane proteins with an Nout-Cin orientation, providing functional insight into the IMS contribution to redox-regulated fusion events.
Title: A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space.
The results may suggest that TP53BP1 and MFN1 frameshift mutations and their intratumoral heterogeneity (ITH) could contribute to cancer development by inhibiting the TSG activities.
Title: Intratumoral heterogeneity for frameshift mutations of TP53BP1 and MFN1 genes in colorectal cancers.
The results show that a metabolic shift from glycolysis in young to mitochondrial respiration in old normal human fibroblasts occurs during chronological lifespan, and MFN1 and OPA1 regulate this process.
Title: Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration during aging.
mitochondria elongation under hypoxic condition is regulated through SIRT1-mediated MFN1 deacetylation and accumulation.
Title: Mitochondria elongation is mediated through SIRT1-mediated MFN1 stabilization.
Regulation of Mfn1 by MGRN1 and the proteasome modulates mitochondrial fusion.
Title: Regulation of Mitofusin1 by Mahogunin Ring Finger-1 and the proteasome modulates mitochondrial fusion.
SLC25A46 is a new component in mitochondrial dynamics that serves as a regulator for MFN1/2 oligomerization.
Title: Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria.
MFN1-positive expression could be seen mainly in ganglion cells after 1 week of minus lens intervention, and with time extension, more and more positive cells appeared in the rod-cone cell and bipolar cell layer, and this phenomenon could not be found in the normal control eyes.
Title: The investigation on the role of mitochondrial fusion protein 1 in the development of myopia.
crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis; mechanistic model for MFN1-mediated mitochondrial tethering is proposed; results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders
Title: MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Factors involved in megakaryocyte development and platelet production, organism-specific biosystem (from REACTOME)
Factors involved in megakaryocyte development and platelet production, organism-specific biosystemMegakaryocytes (MKs) give rise to circulating platelets (thrombocytes) through terminal differentiation of MKs which release cytoplasmic fragments as circulating platelets. As MKs mature they underg...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Mitophagy, organism-specific biosystem (from REACTOME)
Mitophagy, organism-specific biosystemMitophagy is a specific form of autophagy where mitochondria are specifically targeted for degradation by autophagolysosomes.. In mammals there are a number of known mechanisms of mitophagy. One insu...
Mitophagy - animal, organism-specific biosystem (from KEGG)
Mitophagy - animal, organism-specific biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
Mitophagy - animal, conserved biosystem (from KEGG)
Mitophagy - animal, conserved biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
Pink/Parkin Mediated Mitophagy, organism-specific biosystem (from REACTOME)
Pink/Parkin Mediated Mitophagy, organism-specific biosystemThis is the process of selective removal of damaged mitochondria by autophagosomes and subsequent catabolism by lysosomes. In healthy mitochondria, PINK1 is imported to the inner mitochondrial membra...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S3388 (e-PCR)
- UniSTS:52752

RH92241 (e-PCR)
- UniSTS:89045

Homology

Homologs of the MFN1 gene: The MFN1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 260 organisms have orthologs with human gene MFN1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GTP binding	IEA Inferred from Electronic Annotation more info
GTPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
GTPase activity	IDA Inferred from Direct Assay more info	PubMed
GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
GTP metabolic process	IDA Inferred from Direct Assay more info	PubMed
macroautophagy	TAS Traceable Author Statement more info
mitochondrial fusion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrial fusion	IDA Inferred from Direct Assay more info	PubMed
mitochondrial fusion	IMP Inferred from Mutant Phenotype more info	PubMed
mitochondrial membrane fusion	IMP Inferred from Mutant Phenotype more info	PubMed
mitochondrion localization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrion localization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
integral component of membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
intrinsic component of mitochondrial outer membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrial outer membrane	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
outer mitochondrial membrane protein complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitofusin-1

Names: fzo homolog; mitochondrial transmembrane GTPase FZO-2; mitochondrial transmembrane GTPase Fzo-1; putative transmembrane GTPase; transmembrane GTPase MFN1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_033540.3 → NP_284941.2 mitofusin-1

See identical proteins and their annotated locations for NP_284941.2

Status: REVIEWED

Source sequence(s)

AC007620, AI656503, AK000700, BC040557

Consensus CDS

CCDS3228.1

UniProtKB/Swiss-Prot

Q8IWA4

UniProtKB/TrEMBL

A0A0C4DFN1

Related

ENSP00000420617.1, ENST00000471841.6

Conserved Domains (2) summary

cd09912
Location:76 → 328

DLP_2; Dynamin-like protein including dynamins, mitofusins, and guanylate-binding proteins

pfam04799
Location:575 → 734

Fzo_mitofusin; fzo-like conserved region

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p13 Primary Assembly

Range

179347709..179394936

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005247596.4 → XP_005247653.2 mitofusin-1 isoform X1

See identical proteins and their annotated locations for XP_005247653.2

UniProtKB/Swiss-Prot

Q8IWA4

UniProtKB/TrEMBL

A0A0C4DFN1

Related

ENSP00000263969.5, ENST00000263969.9

Conserved Domains (2) summary

cd09912
Location:76 → 328

DLP_2; Dynamin-like protein including dynamins, mitofusins, and guanylate-binding proteins

pfam04799
Location:575 → 734

Fzo_mitofusin; fzo-like conserved region
XM_011512963.3 → XP_011511265.1 mitofusin-1 isoform X2

Related

ENSP00000419926.1, ENST00000474903.1

Conserved Domains (2) summary

pfam04799
Location:428 → 587

Fzo_mitofusin; fzo-like conserved region

cl21455
Location:23 → 181

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_017927.2: Suppressed sequence

Description

NM_017927.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.