MFN1_RAT
ID MFN1_RAT Reviewed; 741 AA.
AC Q8R4Z9;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Mitofusin-1;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q8IWA4};
DE AltName: Full=Mitochondrial transmembrane GTPase FZO1B;
DE AltName: Full=Transmembrane GTPase MFN1;
GN Name=Mfn1; Synonyms=Fzo1b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, MULTIMERIZATION, MUTAGENESIS OF LYS-88, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=14561718; DOI=10.1093/jb/mvg150;
RA Eura Y., Ishihara N., Yokota S., Mihara K.;
RT "Two mitofusin proteins, mammalian homologues of FZO, with distinct
RT functions are both required for mitochondrial fusion.";
RL J. Biochem. 134:333-344(2003).
RN [2]
RP FUNCTION.
RX PubMed=12589796; DOI=10.1016/s0006-291x(03)00050-0;
RA Ishihara N., Jofuku A., Eura Y., Mihara K.;
RT "Regulation of mitochondrial morphology by membrane potential, and DRP1-
RT dependent division and FZO1-dependent fusion reaction in mammalian cells.";
RL Biochem. Biophys. Res. Commun. 301:891-898(2003).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=14592431; DOI=10.1016/j.bbrc.2003.10.008;
RA Honda S., Hirose S.;
RT "Stage-specific enhanced expression of mitochondrial fusion and fission
RT factors during spermatogenesis in rat testis.";
RL Biochem. Biophys. Res. Commun. 311:424-432(2003).
RN [4]
RP INTERACTION WITH VAT1.
RX PubMed=17105775; DOI=10.1242/jcs.03253;
RA Eura Y., Ishihara N., Oka T., Mihara K.;
RT "Identification of a novel protein that regulates mitochondrial fusion by
RT modulating mitofusin (Mfn) protein function.";
RL J. Cell Sci. 119:4913-4925(2006).
CC -!- FUNCTION: Mitochondrial outer membrane GTPase that mediates
CC mitochondrial clustering and fusion (PubMed:14561718, PubMed:12589796).
CC Membrane clustering requires GTPase activity. It may involve a major
CC rearrangement of the coiled coil domains (By similarity). Mitochondria
CC are highly dynamic organelles, and their morphology is determined by
CC the equilibrium between mitochondrial fusion and fission events
CC (PubMed:14561718). Overexpression induces the formation of
CC mitochondrial networks (in vitro) (PubMed:14561718). Has low GTPase
CC activity (By similarity). {ECO:0000250|UniProtKB:Q8IWA4,
CC ECO:0000269|PubMed:12589796, ECO:0000269|PubMed:14561718}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q8IWA4};
CC -!- SUBUNIT: Homodimer, also in the absence of bound GTP. Forms higher
CC oligomers in the presence of a transition state GTP analog (By
CC similarity). Forms homomultimers and heteromultimers with MFN2
CC (PubMed:14561718). Oligomerization is essential for mitochondrion
CC fusion. Component of a high molecular weight multiprotein complex (By
CC similarity). Interacts with VAT1 (PubMed:17105775). Interacts with
CC THG1L; THG1L probably functions as a guanyl-nucleotide exchange
CC factor/GEF, activating MFN1. {ECO:0000250|UniProtKB:Q811U4,
CC ECO:0000250|UniProtKB:Q8IWA4, ECO:0000269|PubMed:14561718,
CC ECO:0000269|PubMed:17105775}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:14561718}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:14561718}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. In brain, it is expressed at weaker
CC level than MFN2, while it is expressed at a higher level than MFN2 in
CC heart and testis. Expressed at high level in elongating spermatids of
CC seminiferous tubules. {ECO:0000269|PubMed:14561718,
CC ECO:0000269|PubMed:14592431}.
CC -!- DOMAIN: A helix bundle is formed by helices from the N-terminal and the
CC C-terminal part of the protein. The GTPase domain cannot be expressed
CC by itself, without the helix bundle. Rearrangement of the helix bundle
CC and/or of the coiled coil domains may bring membranes from adjacent
CC mitochondria into close contact, and thereby play a role in
CC mitochondrial fusion. {ECO:0000250|UniProtKB:Q8IWA4}.
CC -!- PTM: Ubiquitinated by non-degradative ubiquitin by PRKN (By
CC similarity). Deubiquitination by USP30 inhibits mitochondrial fusion
CC (By similarity). Ubiquitinated by MARCHF5. When mitochondria are
CC depolarized and dysfunctional, it is ubiquitinated by a SCF (SKP1-CUL1-
CC F-box protein) E3 ubiquitin-protein ligase complex that contains FBXO7
CC and PRKN (By similarity). {ECO:0000250|UniProtKB:Q811U4,
CC ECO:0000250|UniProtKB:Q8IWA4}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01055}.
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DR EMBL; AB084166; BAB90983.1; -; mRNA.
DR RefSeq; NP_620432.1; NM_138976.1.
DR AlphaFoldDB; Q8R4Z9; -.
DR SMR; Q8R4Z9; -.
DR BioGRID; 251419; 1.
DR STRING; 10116.ENSRNOP00000060265; -.
DR iPTMnet; Q8R4Z9; -.
DR PhosphoSitePlus; Q8R4Z9; -.
DR jPOST; Q8R4Z9; -.
DR PaxDb; Q8R4Z9; -.
DR PRIDE; Q8R4Z9; -.
DR ABCD; Q8R4Z9; 1 sequenced antibody.
DR GeneID; 192647; -.
DR KEGG; rno:192647; -.
DR UCSC; RGD:621460; rat.
DR CTD; 55669; -.
DR RGD; 621460; Mfn1.
DR eggNOG; KOG0448; Eukaryota.
DR InParanoid; Q8R4Z9; -.
DR OrthoDB; 216494at2759; -.
DR PhylomeDB; Q8R4Z9; -.
DR Reactome; R-RNO-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-RNO-9013419; RHOT2 GTPase cycle.
DR Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production.
DR PRO; PR:Q8R4Z9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0031306; C:intrinsic component of mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0098799; C:outer mitochondrial membrane protein complex; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEP:RGD.
DR GO; GO:0046039; P:GTP metabolic process; ISS:UniProtKB.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; IMP:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0008053; P:mitochondrial fusion; ISS:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; ISS:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:RGD.
DR GO; GO:0090258; P:negative regulation of mitochondrial fission; IMP:RGD.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IMP:RGD.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; IMP:RGD.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:1905395; P:response to flavonoid; IEP:RGD.
DR GO; GO:1902617; P:response to fluoride; IEP:RGD.
DR GO; GO:1990910; P:response to hypobaric hypoxia; IEP:RGD.
DR GO; GO:0010042; P:response to manganese ion; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR045063; Dynamin_N.
DR InterPro; IPR006884; Fzo/mitofusin_HR2.
DR InterPro; IPR030381; G_DYNAMIN_dom.
DR InterPro; IPR027088; Mitofusin-1.
DR InterPro; IPR027094; Mitofusin_fam.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10465; PTHR10465; 1.
DR PANTHER; PTHR10465:SF2; PTHR10465:SF2; 1.
DR Pfam; PF00350; Dynamin_N; 1.
DR Pfam; PF04799; Fzo_mitofusin; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51718; G_DYNAMIN_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; GTP-binding; Hydrolase; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Reference proteome;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..741
FT /note="Mitofusin-1"
FT /id="PRO_0000127674"
FT TOPO_DOM 1..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 585..605
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 606..608
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 609..629
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 630..741
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 72..321
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 9..73
FT /note="Part of a helix bundle domain, formed by helices
FT from N-terminal and C-terminal regions"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT REGION 82..89
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 108..109
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 178..181
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 237..240
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 266
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 338..364
FT /note="Part of a helix bundle domain, formed by helices
FT from N-terminal and C-terminal regions"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT REGION 703..734
FT /note="Part of a helix bundle domain, formed by helices
FT from N-terminal and C-terminal regions"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT COILED 371..408
FT /evidence="ECO:0000255"
FT COILED 677..735
FT /evidence="ECO:0000255"
FT BINDING 85..90
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 237..240
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 284
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 286
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT MUTAGEN 88
FT /note="K->T: Induces partial mitochondria fragmentation;
FT when overexpressed."
FT /evidence="ECO:0000269|PubMed:14561718"
SQ SEQUENCE 741 AA; 83847 MW; 39ED084CDD5D27A3 CRC64;
MAETVSPLKH FVLAKKAITA IFGQLLEFVT EGSHFVEATY RNPELDRIAT EDDLVEIQGY
RNKLAVIGEV LSRRHMKVAF FGRTSSGKSS VINAMLWDKV LPSGIGHTTN CFLSVEGTDG
DKAYLMTEGS DEKKSVKTVN QLAHALHMDK DLKAGCLVHV FWPKAKCALL RDDLVLVDSP
GTDVTTELDI WIDKFCLDAD VFVLVANSES TLMNTEKHFF HKVNERLSKP NIFILNNRWD
ASASEPEYME DVRRQHMERC LHFLVEELKV VSPLEARNRI FFVSAKEVLN SRMNKAQGMP
EGGGALAEGF QARLQEFQNF EQTFEECISQ SAVKTKFEQH TIRAKQILDT VKNILDSVNV
AAAEKRVYSM EEREDQIDRL DFIRNQMNLL TMDVKKKIKE VTEEVANKVS CAMTDEICRL
SVLVDEFCSE FHPTPSVLKV YKSELNKHIE DGMGRNLADR CTSEVNASIL QSQQEIIENL
KPLLPAGIQN KLHTLIPCKK FDLSYDLNCH KLCSDFQEDI VFRFSLGWSS LVHRFLGSTN
AQRVLLGLSE PIFQVPRSLA STPTAPSNPA APDNAAQEEL MITLITGLAS LTSRTSMGII
VVGGVIWKTV GWKLISVTLS MYGALYLYER LTWTTRAKER AFKQQFVNYA TEKLQMIVKF
TSANCSHQVQ QEMATTFARL CQQVDVTQKH LEEEIARLSK EIDQLEKIQN NSKLLRNKAV
QLERELENFS KQFLHPSSGE S
