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Protein

Mitofusin-2

Gene

Mfn2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

GTP + H2O = GDP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi103 – 1108GTPCurated
Nucleotide bindingi199 – 2035GTPCurated
Nucleotide bindingi258 – 2614GTPCurated

GO - Molecular functioni

  • GTPase activity Source: RGD
  • GTPase binding Source: UniProtKB
  • GTP binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Autophagy, Unfolded protein response

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitofusin-2 (EC:3.6.5.-)
Alternative name(s):
Mitochondrial transmembrane GTPase FZO1A
Short name:
Protein HSG
Transmembrane GTPase MFN2
Gene namesi
Name:Mfn2
Synonyms:Fzo1a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi628843. Mfn2.

Subcellular locationi

  • Mitochondrion outer membrane 1 Publication; Multi-pass membrane protein 1 Publication

  • Note: Colocalizes with BAX during apoptosis.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 604604CytoplasmicSequence analysisAdd
BLAST
Transmembranei605 – 62521Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini626 – 6261Mitochondrial intermembraneSequence analysis
Transmembranei627 – 64721Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini648 – 757110CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of mitochondrial outer membrane Source: UniProtKB
  • mitochondrial outer membrane Source: RGD
  • mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi109 – 1091K → T: Induces mitochondria fragmentation when overexpressed. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 757757Mitofusin-2PRO_0000127677Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei111 – 1111Phosphothreonine; by PINK1By similarity
Modified residuei442 – 4421Phosphoserine; by PINK1By similarity

Post-translational modificationi

Phosphorylated by PINK1.By similarity
Ubiquitinated by non-degradative ubiquitin by PARK2, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8R500.
PRIDEiQ8R500.

PTM databases

iPTMnetiQ8R500.
PhosphoSiteiQ8R500.

Expressioni

Tissue specificityi

Ubiquitous. In brain, it is more expressed than MFN1, while it is expressed at a weaker level than MFN1 in heart and testis. Expressed at high level in elongating spermatids of seminiferous tubules. Expression is markedly down-regulated in highly proliferative vascular smooth muscle cells (VSMCs) from the genetic hypertensive animal model SHR, as well as in balloon-injured Wistar Kyoto arteries.3 Publications

Interactioni

Subunit structurei

Forms homomultimers and heteromultimers with MFN1. Oligomerization, which is mediated by the second coiled coil region, may play an essential role in mitochondrion fusion. Interacts with VAT1. Interacts with STOML2; may form heterooligomers. Interacts (phosphorylated) with PARK2.1 Publication

GO - Molecular functioni

  • GTPase binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059463.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini93 – 342250Dynamin-type GAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili406 – 43530Sequence analysisAdd
BLAST
Coiled coili696 – 73843Sequence analysisAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0448. Eukaryota.
COG0699. LUCA.
HOGENOMiHOG000231098.
HOVERGENiHBG052465.
InParanoidiQ8R500.
PhylomeDBiQ8R500.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR022812. Dynamin_SF.
IPR006884. Fzo/mitofusin_HR2.
IPR030381. G_DYNAMIN_dom.
IPR027089. Mitofusin-2.
IPR027094. Mitofusin_fam.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10465. PTHR10465. 1 hit.
PTHR10465:SF1. PTHR10465:SF1. 1 hit.
PfamiPF00350. Dynamin_N. 1 hit.
PF04799. Fzo_mitofusin. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS51718. G_DYNAMIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8R500-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLFSRCNS IVTVKKDKRH MAEVNASPLK HFVTAKKKIN GIFEQLGAYI
60 70 80 90 100
QESAGFLEDT HRNTELDPVT TEEQVLDVKG YLSKVRGISE VLARRHMKVA
110 120 130 140 150
FFGRTSNGKS TVINAMLWDK VLPSGIGHTT NCFLRVGGTD GHEAFLLTEG
160 170 180 190 200
SEEKKSVKTV NQLAHALHQD EQLHAGSLVS VMWPNSKCPL LKDGLVLMDS
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 FERRFEECIS
360 370 380 390 400
QSAVKTKFEQ HTVRAKQIAE AVRLIMDSLH IAAQEQRVYC LEMREERQDR
410 420 430 440 450
LRFIDKQLEL LAQDYKLRIK QMTEEVERQV STAMAEEIRR LSVLVDEYQM
460 470 480 490 500
DFHPSPVVLK VYKNELHRHI EEGLGRNMSD RCSTAIASSL QTMQQDMIDG
510 520 530 540 550
LKPLLPVSVR NQIDMLVPRQ CFSLSYDLNC DKLCADFQED IEFHFSLGWT
560 570 580 590 600
MLVNRFLGPK NSRRALLGYN DQVQRPLPLT PANPSMPPLP QGSLTQEELM
610 620 630 640 650
VSMVTGLASL TSRTSMGILV VGGVVWKAVG WRLIALSFGL YGLLYVYERL
660 670 680 690 700
TWTTRAKERA FKRQFVEYAS EKLQLIISYT GSNCSHQVQQ ELSGTFAHLC
710 720 730 740 750
QQVDITRDNL EQEIAAMNKK VEALDSLQSK AKLLRNKAGW LDSELNMFIH

QYLQPSR
Length:757
Mass (Da):86,123
Last modified:June 1, 2002 - v1
Checksum:iBE8340E0891A7DF4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti183 – 1831W → L in AAB87720 (PubMed:15322553).Curated
Sequence conflicti194 – 1941G → D in AAB87720 (PubMed:15322553).Curated
Sequence conflicti265 – 2651S → P in AAB87720 (PubMed:15322553).Curated
Sequence conflicti404 – 4041I → M in AAB87720 (PubMed:15322553).Curated
Sequence conflicti431 – 4311S → T in AAB87720 (PubMed:15322553).Curated
Sequence conflicti756 – 7561S → G in AAB87720 (PubMed:15322553).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB084165 mRNA. Translation: BAB90982.1.
U41803 mRNA. Translation: AAB87720.3.
UniGeneiRn.8570.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB084165 mRNA. Translation: BAB90982.1.
U41803 mRNA. Translation: AAB87720.3.
UniGeneiRn.8570.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059463.

PTM databases

iPTMnetiQ8R500.
PhosphoSiteiQ8R500.

Proteomic databases

PaxDbiQ8R500.
PRIDEiQ8R500.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi628843. Mfn2.

Phylogenomic databases

eggNOGiKOG0448. Eukaryota.
COG0699. LUCA.
HOGENOMiHOG000231098.
HOVERGENiHBG052465.
InParanoidiQ8R500.
PhylomeDBiQ8R500.

Miscellaneous databases

PROiQ8R500.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR022812. Dynamin_SF.
IPR006884. Fzo/mitofusin_HR2.
IPR030381. G_DYNAMIN_dom.
IPR027089. Mitofusin-2.
IPR027094. Mitofusin_fam.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10465. PTHR10465. 1 hit.
PTHR10465:SF1. PTHR10465:SF1. 1 hit.
PfamiPF00350. Dynamin_N. 1 hit.
PF04799. Fzo_mitofusin. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS51718. G_DYNAMIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion."
    Eura Y., Ishihara N., Yokota S., Mihara K.
    J. Biochem. 134:333-344(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MULTIMERIZATION, MUTAGENESIS OF LYS-109.
    Tissue: Liver.
  2. "Dysregulation of HSG triggers vascular proliferative disorders."
    Chen K.-H., Guo X., Ma D., Guo Y., Li Q., Yang D., Li P., Qiu X., Wen S., Xiao R.-P., Tang J.
    Nat. Cell Biol. 6:872-883(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Strain: SHR and Wistar Kyoto.
    Tissue: Aorta.
  3. "Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells."
    Ishihara N., Jofuku A., Eura Y., Mihara K.
    Biochem. Biophys. Res. Commun. 301:891-898(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Stage-specific enhanced expression of mitochondrial fusion and fission factors during spermatogenesis in rat testis."
    Honda S., Hirose S.
    Biochem. Biophys. Res. Commun. 311:424-432(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity."
    Bach D., Pich S., Soriano F.X., Vega N., Baumgartner B., Oriola J., Daugaard J.R., Lloberas J., Camps M., Zierath J.R., Rabasa-Lhoret R., Wallberg-Henriksson H., Laville M., Palacin M., Vidal H., Rivera F., Brand M., Zorzano A.
    J. Biol. Chem. 278:17190-17197(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function."
    Eura Y., Ishihara N., Oka T., Mihara K.
    J. Cell Sci. 119:4913-4925(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VAT1.

Entry informationi

Entry nameiMFN2_RAT
AccessioniPrimary (citable) accession number: Q8R500
Secondary accession number(s): O09013
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: June 1, 2002
Last modified: January 20, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.