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Protein

Mitofusin-2

Gene

Mfn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12527753, PubMed:23921378, PubMed:23620051). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (By similarity). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. 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). 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 (PubMed:23921556). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (PubMed:23921556).By similarity4 Publications

Catalytic activityi

GTP + H2O = GDP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei305GTPBy similarity1
Binding sitei307GTPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi106 – 111GTPBy similarity6
Nucleotide bindingi258 – 261GTPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Hydrolase
Biological processApoptosis, Autophagy, Unfolded protein response
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5205685 Pink/Parkin Mediated Mitophagy
R-MMU-983231 Factors involved in megakaryocyte development and platelet production

Names & Taxonomyi

Protein namesi
Recommended name:
Mitofusin-2 (EC:3.6.5.-)
Alternative name(s):
Hypertension-related protein 1
Mitochondrial assembly regulatory factor
Short name:
HSG protein
Transmembrane GTPase MFN2
Gene namesi
Name:Mfn2
Synonyms:Kiaa0214, Marf
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2442230 Mfn2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 604CytoplasmicSequence analysisAdd BLAST604
Transmembranei605 – 625Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini626Mitochondrial intermembraneSequence analysis1
Transmembranei627 – 647Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini648 – 757CytoplasmicSequence analysisAdd BLAST110

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice die early during embryonic development (PubMed:12527753). Heart-specific disruption causes cardiomyopathy in aging mice, characterized by dilated hearts that are insensitive to beta-adrenergic stimulation and impaired contractile performance (PubMed:23620051). Mutant cardiomyocytes display mitochondrial enlargement with respiratory impairment (PubMed:23620051).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001276761 – 757Mitofusin-2Add BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei111Phosphothreonine; by PINK1By similarity1
Modified residuei442PhosphoserineCombined sources1
Modified residuei442Phosphoserine; by PINK1By similarity1

Post-translational modificationi

Phosphorylated by PINK1.1 Publication
Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ80U63
PaxDbiQ80U63
PeptideAtlasiQ80U63
PRIDEiQ80U63

PTM databases

iPTMnetiQ80U63
PhosphoSitePlusiQ80U63

Expressioni

Tissue specificityi

Ubiquitous. Expression is markedly reduced in ApoE-knockout mouse atherosclerotic arteries.2 Publications

Gene expression databases

BgeeiENSMUSG00000029020
CleanExiMM_MFN2
ExpressionAtlasiQ80U63 baseline and differential
GenevisibleiQ80U63 MM

Interactioni

Subunit structurei

Forms homomultimers and heteromultimers with MFN1 (PubMed:12527753). Oligomerization is essential for mitochondrion fusion (Probable). Interacts with VAT1 (By similarity). Interacts with STOML2; may form heterooligomers (By similarity). Interacts (phosphorylated) with PRKN (PubMed:23620051). Interacts with EIF2AK3 (By similarity).By similarityCurated2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi228398, 5 interactors
DIPiDIP-60970N
IntActiQ80U63, 8 interactors
MINTiQ80U63
STRINGi10090.ENSMUSP00000030884

Structurei

3D structure databases

ProteinModelPortaliQ80U63
SMRiQ80U63
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini93 – 342Dynamin-type GAdd BLAST250

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 94Part of a helix bundle domain, formed by helices from N-terminal and C-terminal regionsBy similarityAdd BLAST65
Regioni359 – 385Part of a helix bundle domain, formed by helices from N-terminal and C-terminal regionsBy similarityAdd BLAST27
Regioni722 – 753Part of a helix bundle domain, formed by helices from N-terminal and C-terminal regionsBy similarityAdd BLAST32

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili406 – 434Sequence analysisAdd BLAST29
Coiled coili696 – 738Sequence analysisAdd BLAST43

Domaini

A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0448 Eukaryota
COG0699 LUCA
GeneTreeiENSGT00390000013727
HOVERGENiHBG052465
InParanoidiQ80U63
KOiK06030
OMAiEQRVYCL
OrthoDBiEOG091G02ES
PhylomeDBiQ80U63
TreeFamiTF314289

Family and domain databases

InterProiView protein in InterPro
IPR022812 Dynamin_SF
IPR006884 Fzo/mitofusin_HR2
IPR030381 G_DYNAMIN_dom
IPR027089 Mitofusin-2
IPR027094 Mitofusin_fam
IPR027417 P-loop_NTPase
PANTHERiPTHR10465 PTHR10465, 1 hit
PTHR10465:SF1 PTHR10465:SF1, 1 hit
PfamiView protein in Pfam
PF00350 Dynamin_N, 1 hit
PF04799 Fzo_mitofusin, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51718 G_DYNAMIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80U63-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLLFSRCNS IVTVKKDKRH MAEVNASPLK HFVTAKKKIN GIFEQLGAYI
60 70 80 90 100
QESASFLEDT HRNTELDPVT TEEQVLDVKG YLSKVRGISE VLARRHMKVA
110 120 130 140 150
FFGRTSNGKS TVINAMLWDK VLPSGIGHTT NCFLRVGGTD GHEAFLLTEG
160 170 180 190 200
SEEKKSVKTV NQLAHALHQD EQLHAGSMVS VMWPNSKCPL LKDDLVLMDS
210 220 230 240 250
PGIDVTTELD SWIDKFCLDA DVFVLVANSE STLMQTEKQF FHKVSERLSR
260 270 280 290 300
PNIFILNNRW DASASEPEYM EEVRRQHMER CTSFLVDELG VVDRAQAGDR
310 320 330 340 350
IFFVSAKEVL SARVQKAQGM PEGGGALAEG FQVRMFEFQN FERQFEECIS
360 370 380 390 400
QSAVKTKFEQ HTVRAKQIAE AVRLIMDSLH IAAQEQRVYC LEMREERQDR
410 420 430 440 450
LRFIDKQLEL LAQDYKLRIK QITEEVERQV STAMAEEIRR LSVLVDEYQM
460 470 480 490 500
DFHPSPVVLK VYKNELHRHI EEGLGRNLSD RCSTAIASSL QTMQQDMIDG
510 520 530 540 550
LKPLLPVSMR NQIDMLVPRQ CFSLSYDLNC DKLCADFQED IEFHFSLGWT
560 570 580 590 600
MLVNRFLGPK NSRRALLGYS DQVQRPLPLT PANPSMPPLP QSSLTQEELM
610 620 630 640 650
VSMVTGLASL TSRTSMGILV VGGVVWKAVG WRLIALSFGL YGLLYVYERL
660 670 680 690 700
TWTTKAKERA FKRQFVEYAS EKLQLIISYT GSNCSHQVQQ ELSGTFAHLC
710 720 730 740 750
QQVDITRDNL EQEIAAMNKK VEALDSLQSR AKLLRNKAGW LDSELNMFTH

QYLQPSR
Length:757
Mass (Da):86,188
Last modified:May 24, 2004 - v3
Checksum:i25B0EAE8301F4D1A
GO
Isoform 2 (identifier: Q80U63-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     573-605: VQRPLPLTPANPSMPPLPQSSLTQEELMVSMVT → ARSSFPWCIMGDHPDTRYGSQSTTAGVLRAEAI
     606-757: Missing.

Note: No experimental confirmation available.
Show »
Length:605
Mass (Da):68,938
Checksum:iEDCB31AC12D60912
GO

Sequence cautioni

The sequence BAC65502 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti123P → L in AAH46503 (PubMed:15489334).Curated1
Sequence conflicti167L → I in BAC33826 (PubMed:16141072).Curated1
Sequence conflicti332Q → K in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti344Q → R in BAB39351 (Ref. 3) Curated1
Sequence conflicti344Q → R in AAK66559 (PubMed:15322553).Curated1
Sequence conflicti437E → G in BAB39351 (Ref. 3) Curated1
Sequence conflicti570S → N in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti592S → G in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti601V → G in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti633 – 635LIA → IIP in AAK27416 (PubMed:12598526).Curated3
Sequence conflicti656A → T in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti659R → K in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti666V → A in AAK66559 (PubMed:15322553).Curated1
Sequence conflicti667E → D in BAB39351 (Ref. 3) Curated1
Sequence conflicti676I → T in BAB39351 (Ref. 3) Curated1
Sequence conflicti697A → G in AAK27416 (PubMed:12598526).Curated1
Sequence conflicti730R → K in AAK27416 (PubMed:12598526).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010365573 – 605VQRPL…VSMVT → ARSSFPWCIMGDHPDTRYGS QSTTAGVLRAEAI in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_010366606 – 757Missing in isoform 2. 1 PublicationAdd BLAST152

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY123975 mRNA Translation: AAM88577.1
AY028170 mRNA Translation: AAK27416.1
AB048831 mRNA Translation: BAB39351.1
AF384100 mRNA Translation: AAK66559.1
AK042080 mRNA Translation: BAE20620.1
AK049583 mRNA Translation: BAC33826.1
AK052689 mRNA Translation: BAC35096.1
AK122220 Transcribed RNA Translation: BAC65502.2 Different initiation.
AL607066 Genomic DNA No translation available.
BC046503 mRNA Translation: AAH46503.1
CCDSiCCDS38965.1 [Q80U63-1]
RefSeqiNP_001272849.1, NM_001285920.1 [Q80U63-1]
NP_001272850.1, NM_001285921.1 [Q80U63-1]
NP_001272851.1, NM_001285922.1 [Q80U63-1]
NP_001272852.1, NM_001285923.1 [Q80U63-1]
NP_573464.2, NM_133201.3 [Q80U63-1]
XP_006538672.1, XM_006538609.3 [Q80U63-1]
XP_006538673.1, XM_006538610.2
XP_006538674.1, XM_006538611.3
UniGeneiMm.154312
Mm.437499
Mm.488699

Genome annotation databases

EnsembliENSMUST00000030884; ENSMUSP00000030884; ENSMUSG00000029020 [Q80U63-1]
ENSMUST00000105714; ENSMUSP00000101339; ENSMUSG00000029020 [Q80U63-2]
ENSMUST00000105715; ENSMUSP00000101340; ENSMUSG00000029020 [Q80U63-1]
ENSMUST00000105716; ENSMUSP00000101341; ENSMUSG00000029020 [Q80U63-1]
GeneIDi170731
KEGGimmu:170731
UCSCiuc008vtg.2 mouse [Q80U63-1]
uc008vtj.2 mouse [Q80U63-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMFN2_MOUSE
AccessioniPrimary (citable) accession number: Q80U63
Secondary accession number(s): A2A7Y7
, A8Y5E4, Q3V3B8, Q80WP4, Q80XK3, Q8BHF0, Q8BKV5, Q8R535, Q923X2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: March 28, 2018
This is version 132 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health