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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

Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:14561718, PubMed:15322553, PubMed:12589796, PubMed:12598526). 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 (PubMed:12598526). Plays an important role in the regulation of vascular smooth muscle cell proliferation (PubMed:15322553). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PRKN recruitment to dysfunctional mitochondria (By similarity). 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).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

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

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • autophagy Source: UniProtKB-KW
  • cellular response to oxygen-glucose deprivation Source: RGD
  • intracellular distribution of mitochondria Source: RGD
  • mitochondrial fusion Source: RGD
  • mitochondrial membrane organization Source: UniProtKB
  • mitochondrion morphogenesis Source: RGD
  • mitochondrion organization Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of release of cytochrome c from mitochondria Source: RGD
  • negative regulation of smooth muscle cell proliferation Source: UniProtKB
  • positive regulation of dendritic spine morphogenesis Source: RGD
  • positive regulation of membrane potential Source: RGD
  • protein targeting to mitochondrion Source: UniProtKB
  • response to axon injury Source: RGD
  • response to flavonoid Source: RGD
  • response to hypobaric hypoxia Source: RGD
  • response to muscle activity Source: RGD
  • response to unfolded protein Source: UniProtKB-KW

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Autophagy, Unfolded protein response
LigandGTP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi628843. Mfn2.

Subcellular locationi

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

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • integral component of membrane Source: GO_Central
  • intrinsic component of mitochondrial outer membrane Source: UniProtKB
  • mitochondrial outer membrane Source: RGD
  • mitochondrion Source: RGD

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109K → T: Induces mitochondria fragmentation when overexpressed. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001276771 – 757Mitofusin-2Add BLAST757

Amino acid modifications

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

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8R500.
PRIDEiQ8R500.

PTM databases

iPTMnetiQ8R500.
PhosphoSitePlusiQ8R500.

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 (PubMed:14561718). Oligomerization is essential for mitochondrion fusion (Probable). Interacts with VAT1 (PubMed:17105775). Interacts with STOML2; may form heterooligomers (By similarity). Interacts (phosphorylated) with PRKN (By similarity). Interacts with EIF2AK3 (By similarity).By similarityCurated2 Publications

GO - Molecular functioni

  • GTPase binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059463.

Structurei

3D structure databases

SMRiQ8R500.
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 – 435Sequence analysisAdd BLAST30
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.
HOGENOMiHOG000231098.
HOVERGENiHBG052465.
InParanoidiQ8R500.
PhylomeDBiQ8R500.

Family and domain databases

InterProiView protein in InterPro
IPR022812. Dynamin_SF.
IPR006884. Fzo/mitofusin_HR2.
IPR030381. G_DYNAMIN_dom.
IPR027089. Mitofusin-2.
IPR027417. P-loop_NTPase.
PANTHERiPTHR10465:SF9. PTHR10465:SF9. 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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti183W → L in AAB87720 (PubMed:15322553).Curated1
Sequence conflicti194G → D in AAB87720 (PubMed:15322553).Curated1
Sequence conflicti265S → P in AAB87720 (PubMed:15322553).Curated1
Sequence conflicti404I → M in AAB87720 (PubMed:15322553).Curated1
Sequence conflicti431S → T in AAB87720 (PubMed:15322553).Curated1
Sequence conflicti756S → G in AAB87720 (PubMed:15322553).Curated1

Sequence databases

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

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.

Entry informationi

Entry nameiMFN2_RAT
AccessioniPrimary (citable) accession number: Q8R500
Secondary accession number(s): O09013
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: June 1, 2002
Last modified: July 5, 2017
This is version 98 of the entry and version 1 of the sequence. See 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