MFN2_MOUSE
ID MFN2_MOUSE Reviewed; 757 AA.
AC Q80U63; A2A7Y7; A8Y5E4; Q3V3B8; Q80WP4; Q80XK3; Q8BHF0; Q8BKV5; Q8R535;
AC Q923X2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Mitofusin-2;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:O95140};
DE AltName: Full=Hypertension-related protein 1;
DE AltName: Full=Mitochondrial assembly regulatory factor;
DE Short=HSG protein;
DE AltName: Full=Transmembrane GTPase MFN2;
GN Name=Mfn2; Synonyms=Kiaa0214, Marf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DISRUPTION PHENOTYPE,
RP MULTIMERIZATION, AND SUBUNIT.
RC STRAIN=FVB/NJ;
RX PubMed=12527753; DOI=10.1083/jcb.200211046;
RA Chen H., Detmer S.A., Ewald A.J., Griffin E.E., Fraser S.E., Chan D.C.;
RT "Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and
RT are essential for embryonic development.";
RL J. Cell Biol. 160:189-200(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12598526; DOI=10.1074/jbc.m212754200;
RA Bach D., Pich S., Soriano F.X., Vega N., Baumgartner B., Oriola J.,
RA Daugaard J.R., Lloberas J., Camps M., Zierath J.R., Rabasa-Lhoret R.,
RA Wallberg-Henriksson H., Laville M., Palacin M., Vidal H., Rivera F.,
RA Brand M., Zorzano A.;
RT "Mitofusin-2 determines mitochondrial network architecture and
RT mitochondrial metabolism. A novel regulatory mechanism altered in
RT obesity.";
RL J. Biol. Chem. 278:17190-17197(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Honda S., Hirose S.;
RT "Characterization of mouse fzo.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=15322553; DOI=10.1038/ncb1161;
RA Chen K.-H., Guo X., Ma D., Guo Y., Li Q., Yang D., Li P., Qiu X., Wen S.,
RA Xiao R.-P., Tang J.;
RT "Dysregulation of HSG triggers vascular proliferative disorders.";
RL Nat. Cell Biol. 6:872-883(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [6]
RP SEQUENCE REVISION.
RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 421-428, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=11950885; DOI=10.1242/jcs.115.8.1663;
RA Rojo M., Legros F., Chateau D., Lombes A.;
RT "Membrane topology and mitochondrial targeting of mitofusins, ubiquitous
RT mammalian homologs of the transmembrane GTPase Fzo.";
RL J. Cell Sci. 115:1663-1674(2002).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP FUNCTION IN UPR, AND INTERACTION WITH EIF2AK3.
RX PubMed=23921556; DOI=10.1038/emboj.2013.168;
RA Munoz J.P., Ivanova S., Sanchez-Wandelmer J., Martinez-Cristobal P.,
RA Noguera E., Sancho A., Diaz-Ramos A., Hernandez-Alvarez M.I., Sebastian D.,
RA Mauvezin C., Palacin M., Zorzano A.;
RT "Mfn2 modulates the UPR and mitochondrial function via repression of
RT PERK.";
RL EMBO J. 32:2348-2361(2013).
RN [14]
RP FUNCTION.
RX PubMed=23921378; DOI=10.1074/jbc.m113.479873;
RA Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D.,
RA Ryan M.T.;
RT "MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment
RT and are specific for mitochondrial fission.";
RL J. Biol. Chem. 288:27584-27593(2013).
RN [15]
RP FUNCTION IN MITOPHAGY, INTERACTION WITH PRKN, PHOSPHORYLATION AT THR-111
RP AND SER-442, UBIQUITINATION BY PRKN, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=23620051; DOI=10.1126/science.1231031;
RA Chen Y., Dorn G.W. II;
RT "PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged
RT mitochondria.";
RL Science 340:471-475(2013).
RN [16]
RP UBIQUITINATION, AND DEUBIQUITINATION.
RX PubMed=24513856; DOI=10.1038/cr.2014.20;
RA Yue W., Chen Z., Liu H., Yan C., Chen M., Feng D., Yan C., Wu H., Du L.,
RA Wang Y., Liu J., Huang X., Xia L., Liu L., Wang X., Jin H., Wang J.,
RA Song Z., Hao X., Chen Q.;
RT "A small natural molecule promotes mitochondrial fusion through inhibition
RT of the deubiquitinase USP30.";
RL Cell Res. 24:482-496(2014).
CC -!- FUNCTION: Mitochondrial outer membrane GTPase that mediates
CC mitochondrial clustering and fusion (PubMed:12527753, PubMed:23921378,
CC PubMed:23620051). Mitochondria are highly dynamic organelles, and their
CC morphology is determined by the equilibrium between mitochondrial
CC fusion and fission events. Overexpression induces the formation of
CC mitochondrial networks. Membrane clustering requires GTPase activity
CC and may involve a major rearrangement of the coiled coil domains (By
CC similarity). Plays a central role in mitochondrial metabolism and may
CC be associated with obesity and/or apoptosis processes. Plays an
CC important role in the regulation of vascular smooth muscle cell
CC proliferation (By similarity). Involved in the clearance of damaged
CC mitochondria via selective autophagy (mitophagy). Is required for PRKN
CC recruitment to dysfunctional mitochondria (PubMed:23620051). Involved
CC in the control of unfolded protein response (UPR) upon ER stress
CC including activation of apoptosis and autophagy during ER stress
CC (PubMed:23921556). Acts as an upstream regulator of EIF2AK3 and
CC suppresses EIF2AK3 activation under basal conditions (PubMed:23921556).
CC {ECO:0000250|UniProtKB:O95140, ECO:0000250|UniProtKB:Q8R500,
CC ECO:0000269|PubMed:12527753, ECO:0000269|PubMed:23620051,
CC ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:23921556}.
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:O95140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:O95140};
CC -!- SUBUNIT: Forms homomultimers and heteromultimers with MFN1
CC (PubMed:12527753). Oligomerization is essential for mitochondrion
CC fusion (Probable). Interacts with VAT1 (By similarity). Interacts with
CC STOML2; may form heterooligomers (By similarity). Interacts
CC (phosphorylated) with PRKN (PubMed:23620051). Interacts with EIF2AK3
CC (By similarity). Interacts with THG1L; THG1L probably functions as a
CC guanyl-nucleotide exchange factor/GEF, activating MFN2.
CC {ECO:0000250|UniProtKB:O95140, ECO:0000250|UniProtKB:Q8R500,
CC ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23921556, ECO:0000305}.
CC -!- INTERACTION:
CC Q80U63; O08734: Bak1; NbExp=2; IntAct=EBI-8437663, EBI-822441;
CC Q80U63; Q9Z2B5: Eif2ak3; NbExp=2; IntAct=EBI-8437663, EBI-1226344;
CC Q80U63; Q16611: BAK1; Xeno; NbExp=3; IntAct=EBI-8437663, EBI-519866;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:O95140}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O95140}. Note=Colocalizes with BAX during
CC apoptosis. {ECO:0000250|UniProtKB:O95140}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80U63-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80U63-2; Sequence=VSP_010365, VSP_010366;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expression is markedly reduced in ApoE-
CC knockout mouse atherosclerotic arteries. {ECO:0000269|PubMed:11950885,
CC ECO:0000269|PubMed:15322553}.
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: Phosphorylated by PINK1. {ECO:0000269|PubMed:23620051}.
CC -!- PTM: Ubiquitinated by non-degradative ubiquitin by PRKN, promoting
CC mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial
CC fusion (PubMed:23620051, PubMed:24513856). Ubiquitinated by HUWE1 when
CC dietary stearate (C18:0) levels are low; ubiquitination inhibits
CC mitochondrial fusion (By similarity). {ECO:0000250|UniProtKB:O95140,
CC ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:24513856}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice die early during embryonic
CC development (PubMed:12527753). Heart-specific disruption causes
CC cardiomyopathy in aging mice, characterized by dilated hearts that are
CC insensitive to beta-adrenergic stimulation and impaired contractile
CC performance (PubMed:23620051). Mutant cardiomyocytes display
CC mitochondrial enlargement with respiratory impairment
CC (PubMed:23620051). {ECO:0000269|PubMed:23620051}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01055}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65502.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY123975; AAM88577.1; -; mRNA.
DR EMBL; AY028170; AAK27416.1; -; mRNA.
DR EMBL; AB048831; BAB39351.1; -; mRNA.
DR EMBL; AF384100; AAK66559.1; -; mRNA.
DR EMBL; AK042080; BAE20620.1; -; mRNA.
DR EMBL; AK049583; BAC33826.1; -; mRNA.
DR EMBL; AK052689; BAC35096.1; -; mRNA.
DR EMBL; AK122220; BAC65502.2; ALT_INIT; Transcribed_RNA.
DR EMBL; AL607066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC046503; AAH46503.1; -; mRNA.
DR CCDS; CCDS38965.1; -. [Q80U63-1]
DR RefSeq; NP_001272849.1; NM_001285920.1. [Q80U63-1]
DR RefSeq; NP_001272850.1; NM_001285921.1. [Q80U63-1]
DR RefSeq; NP_001272851.1; NM_001285922.1. [Q80U63-1]
DR RefSeq; NP_001272852.1; NM_001285923.1. [Q80U63-1]
DR RefSeq; NP_573464.2; NM_133201.3. [Q80U63-1]
DR RefSeq; XP_006538672.1; XM_006538609.3. [Q80U63-1]
DR RefSeq; XP_006538673.1; XM_006538610.2.
DR RefSeq; XP_006538674.1; XM_006538611.3.
DR AlphaFoldDB; Q80U63; -.
DR SMR; Q80U63; -.
DR BioGRID; 228398; 10.
DR DIP; DIP-60970N; -.
DR IntAct; Q80U63; 8.
DR MINT; Q80U63; -.
DR STRING; 10090.ENSMUSP00000101341; -.
DR GuidetoPHARMACOLOGY; 3131; -.
DR iPTMnet; Q80U63; -.
DR PhosphoSitePlus; Q80U63; -.
DR EPD; Q80U63; -.
DR jPOST; Q80U63; -.
DR MaxQB; Q80U63; -.
DR PaxDb; Q80U63; -.
DR PeptideAtlas; Q80U63; -.
DR PRIDE; Q80U63; -.
DR ProteomicsDB; 295893; -. [Q80U63-1]
DR ProteomicsDB; 295894; -. [Q80U63-2]
DR ABCD; Q80U63; 1 sequenced antibody.
DR Antibodypedia; 28394; 762 antibodies from 45 providers.
DR DNASU; 170731; -.
DR Ensembl; ENSMUST00000030884; ENSMUSP00000030884; ENSMUSG00000029020. [Q80U63-1]
DR Ensembl; ENSMUST00000105714; ENSMUSP00000101339; ENSMUSG00000029020. [Q80U63-2]
DR Ensembl; ENSMUST00000105715; ENSMUSP00000101340; ENSMUSG00000029020. [Q80U63-1]
DR Ensembl; ENSMUST00000105716; ENSMUSP00000101341; ENSMUSG00000029020. [Q80U63-1]
DR GeneID; 170731; -.
DR KEGG; mmu:170731; -.
DR UCSC; uc008vtg.2; mouse. [Q80U63-1]
DR UCSC; uc008vtj.2; mouse. [Q80U63-2]
DR CTD; 9927; -.
DR MGI; MGI:2442230; Mfn2.
DR VEuPathDB; HostDB:ENSMUSG00000029020; -.
DR eggNOG; KOG0448; Eukaryota.
DR GeneTree; ENSGT00390000013727; -.
DR HOGENOM; CLU_021212_2_0_1; -.
DR InParanoid; Q80U63; -.
DR OMA; LEFRFSF; -.
DR OrthoDB; 216494at2759; -.
DR PhylomeDB; Q80U63; -.
DR TreeFam; TF314289; -.
DR Reactome; R-MMU-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-MMU-9013419; RHOT2 GTPase cycle.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 170731; 14 hits in 74 CRISPR screens.
DR ChiTaRS; Mfn2; mouse.
DR PRO; PR:Q80U63; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80U63; protein.
DR Bgee; ENSMUSG00000029020; Expressed in interventricular septum and 253 other tissues.
DR ExpressionAtlas; Q80U63; baseline and differential.
DR Genevisible; Q80U63; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031306; C:intrinsic component of mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0043394; F:proteoglycan binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001825; P:blastocyst formation; IMP:MGI.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IMP:MGI.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; ISO:MGI.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISO:MGI.
DR GO; GO:0008053; P:mitochondrial fusion; IMP:UniProtKB.
DR GO; GO:0007006; P:mitochondrial membrane organization; ISS:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; ISS:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; ISO:MGI.
DR GO; GO:0007005; P:mitochondrion organization; ISO:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045792; P:negative regulation of cell size; ISO:MGI.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0090258; P:negative regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0060299; P:negative regulation of sarcomere organization; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901857; P:positive regulation of cellular respiration; ISO:MGI.
DR GO; GO:0035563; P:positive regulation of chromatin binding; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:2000866; P:positive regulation of estradiol secretion; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR GO; GO:0010729; P:positive regulation of hydrogen peroxide biosynthetic process; ISO:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:2000386; P:positive regulation of ovarian follicle development; ISO:MGI.
DR GO; GO:2000872; P:positive regulation of progesterone secretion; ISO:MGI.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:MGI.
DR GO; GO:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; ISO:MGI.
DR GO; GO:0006626; P:protein targeting to mitochondrion; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
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; IPR027089; Mitofusin-2.
DR InterPro; IPR027094; Mitofusin_fam.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10465; PTHR10465; 1.
DR PANTHER; PTHR10465:SF1; PTHR10465:SF1; 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 Alternative splicing; Apoptosis; Autophagy; Coiled coil;
KW Developmental protein; Direct protein sequencing; GTP-binding; Hydrolase;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation; Unfolded protein response.
FT CHAIN 1..757
FT /note="Mitofusin-2"
FT /id="PRO_0000127676"
FT TOPO_DOM 1..604
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 605..625
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 626
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..647
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 648..757
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 93..342
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 30..94
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 103..110
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 129..130
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 199..202
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 258..261
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 288
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 359..385
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 722..753
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 406..434
FT /evidence="ECO:0000255"
FT COILED 696..738
FT /evidence="ECO:0000255"
FT BINDING 106..111
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 258..261
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 305
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 307
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT MOD_RES 111
FT /note="Phosphothreonine; by PINK1"
FT /evidence="ECO:0000250|UniProtKB:O95140"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 573..605
FT /note="VQRPLPLTPANPSMPPLPQSSLTQEELMVSMVT -> ARSSFPWCIMGDHPD
FT TRYGSQSTTAGVLRAEAI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010365"
FT VAR_SEQ 606..757
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010366"
FT CONFLICT 123
FT /note="P -> L (in Ref. 9; AAH46503)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="L -> I (in Ref. 7; BAC33826)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="Q -> K (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="Q -> R (in Ref. 3; BAB39351 and 4; AAK66559)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="E -> G (in Ref. 3; BAB39351)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="S -> N (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="S -> G (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 601
FT /note="V -> G (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 633..635
FT /note="LIA -> IIP (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 656
FT /note="A -> T (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="R -> K (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 666
FT /note="V -> A (in Ref. 4; AAK66559)"
FT /evidence="ECO:0000305"
FT CONFLICT 667
FT /note="E -> D (in Ref. 3; BAB39351)"
FT /evidence="ECO:0000305"
FT CONFLICT 676
FT /note="I -> T (in Ref. 3; BAB39351)"
FT /evidence="ECO:0000305"
FT CONFLICT 697
FT /note="A -> G (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="R -> K (in Ref. 2; AAK27416)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 757 AA; 86188 MW; 25B0EAE8301F4D1A CRC64;
MSLLFSRCNS IVTVKKDKRH MAEVNASPLK HFVTAKKKIN GIFEQLGAYI QESASFLEDT
HRNTELDPVT TEEQVLDVKG YLSKVRGISE VLARRHMKVA FFGRTSNGKS TVINAMLWDK
VLPSGIGHTT NCFLRVGGTD GHEAFLLTEG SEEKKSVKTV NQLAHALHQD EQLHAGSMVS
VMWPNSKCPL LKDDLVLMDS PGIDVTTELD SWIDKFCLDA DVFVLVANSE STLMQTEKQF
FHKVSERLSR PNIFILNNRW DASASEPEYM EEVRRQHMER CTSFLVDELG VVDRAQAGDR
IFFVSAKEVL SARVQKAQGM PEGGGALAEG FQVRMFEFQN FERQFEECIS QSAVKTKFEQ
HTVRAKQIAE AVRLIMDSLH IAAQEQRVYC LEMREERQDR LRFIDKQLEL LAQDYKLRIK
QITEEVERQV STAMAEEIRR LSVLVDEYQM DFHPSPVVLK VYKNELHRHI EEGLGRNLSD
RCSTAIASSL QTMQQDMIDG LKPLLPVSMR NQIDMLVPRQ CFSLSYDLNC DKLCADFQED
IEFHFSLGWT MLVNRFLGPK NSRRALLGYS DQVQRPLPLT PANPSMPPLP QSSLTQEELM
VSMVTGLASL TSRTSMGILV VGGVVWKAVG WRLIALSFGL YGLLYVYERL TWTTKAKERA
FKRQFVEYAS EKLQLIISYT GSNCSHQVQQ ELSGTFAHLC QQVDITRDNL EQEIAAMNKK
VEALDSLQSR AKLLRNKAGW LDSELNMFTH QYLQPSR
