ID MFN1_MOUSE Reviewed; 741 AA. AC Q811U4; Q3URC4; Q811D5; Q8CEY6; Q99M10; Q9D395; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 16-SEP-2015, entry version 109. DE RecName: Full=Mitofusin-1; DE EC=3.6.5.-; DE AltName: Full=Transmembrane GTPase MFN1; GN Name=Mfn1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND RP MULTIMERIZATION. RC STRAIN=FVB; RX PubMed=12527753; DOI=10.1083/jcb.200211046; RA Chen H., Detmer S.A., Ewald A.J., Griffin E.E., Fraser S.E., RA Chan D.C.; RT "Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion RT and are essential for embryonic development."; RL J. Cell Biol. 160:189-200(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Hippocampus, Medulla oblongata, and Tongue; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Liver, and Mammary tumor; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP TISSUE SPECIFICITY. RX PubMed=11950885; RA Rojo M., Legros F., Chateau D., Lombes A.; RT "Membrane topology and mitochondrial targeting of mitofusins, RT ubiquitous mammalian homologs of the transmembrane GTPase Fzo."; RL J. Cell Sci. 115:1663-1674(2002). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and 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 RT expression."; RL Cell 143:1174-1189(2010). RN [6] RP DISRUPTION 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 RT damaged mitochondria."; RL Science 340:471-475(2013). RN [7] 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., RA Du L., Wang Y., Liu J., Huang X., Xia L., Liu L., Wang X., Jin H., RA Wang J., Song Z., Hao X., Chen Q.; RT "A small natural molecule promotes mitochondrial fusion through RT inhibition of the deubiquitinase USP30."; RL Cell Res. 24:482-496(2014). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 660-735, FUNCTION, SUBUNIT, RP AND COILED-COIL DOMAINS. RX PubMed=15297672; DOI=10.1126/science.1099793; RA Koshiba T., Detmer S.A., Kaiser J.T., Chen H., McCaffery J.M., RA Chan D.C.; RT "Structural basis of mitochondrial tethering by mitofusin complexes."; RL Science 305:858-862(2004). CC -!- FUNCTION: Essential transmembrane GTPase, which mediates CC mitochondrial fusion. Fusion of mitochondria occurs in many cell CC types and constitutes an important step in mitochondria CC morphology, which is balanced between fusion and fission. MFN1 CC acts independently of the cytoskeleton. Overexpression induces the CC formation of mitochondrial networks. {ECO:0000269|PubMed:12527753, CC ECO:0000269|PubMed:15297672}. CC -!- CATALYTIC ACTIVITY: GTP + H(2)O = GDP + phosphate. CC -!- SUBUNIT: Forms homomultimers and heteromultimers with MFN2. CC Multimerization, which is mediated by the second coiled coil CC region, may play an essential role in mitochondrion fusion. CC Participates in a high molecular weight multiprotein complex. CC Interacts with VAT1 (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q5S007:LRRK2 (xeno); NbExp=3; IntAct=EBI-9029118, EBI-5323863; CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; CC Multi-pass membrane protein {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Widely expressed. CC {ECO:0000269|PubMed:11950885}. CC -!- DEVELOPMENTAL STAGE: Expressed in E8.5, E9.5, E10.5 and E11.5 CC embryos. {ECO:0000269|PubMed:12527753}. CC -!- PTM: Ubiquitinated by MARCH5. When mitochondria are depolarized CC and dysfunctional, it is ubiquitinated by a SCF (SKP1-CUL1-F-box CC protein) E3 ubiquitin-protein ligase complex that contains FBXO7 CC and PARK2. Ubiquitinated by non-degradative ubiquitin by PARK2, CC promoting mitochondrial fusion; deubiquitination by USP30 inhibits CC mitochondrial fusion (PubMed:24513856). CC {ECO:0000269|PubMed:24513856}. CC -!- DISRUPTION PHENOTYPE: In cardiomyocytes, no effect on CC mitochondrial morphometry or respiratory function. CC {ECO:0000269|PubMed:23620051}. CC -!- MISCELLANEOUS: MFN1 deficient mice die early during embryonic CC development, due to altered mitochondria morphology, which are CC fragmented, showing that mitochondrial fusion is essential for CC embryonic development. CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase CC superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 dynamin-type G (guanine nucleotide-binding) CC domain. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH47050.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAC25260.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY174062; AAO34660.1; -; mRNA. DR EMBL; AK009490; BAC25260.1; ALT_INIT; mRNA. DR EMBL; AK018181; BAB31111.1; -; mRNA. DR EMBL; AK141611; BAE24764.1; -; mRNA. DR EMBL; BC002133; AAH02133.1; -; mRNA. DR EMBL; BC047050; AAH47050.1; ALT_INIT; mRNA. DR EMBL; BC056641; AAH56641.1; -; mRNA. DR CCDS; CCDS17296.1; -. DR RefSeq; NP_077162.2; NM_024200.4. DR UniGene; Mm.290414; -. DR PDB; 1T3J; X-ray; 2.50 A; A=660-735. DR PDBsum; 1T3J; -. DR ProteinModelPortal; Q811U4; -. DR SMR; Q811U4; 674-735. DR BioGrid; 212170; 2. DR DIP; DIP-60969N; -. DR IntAct; Q811U4; 1. DR STRING; 10090.ENSMUSP00000088801; -. DR PhosphoSite; Q811U4; -. DR MaxQB; Q811U4; -. DR PaxDb; Q811U4; -. DR PRIDE; Q811U4; -. DR Ensembl; ENSMUST00000091257; ENSMUSP00000088801; ENSMUSG00000027668. DR Ensembl; ENSMUST00000118286; ENSMUSP00000113251; ENSMUSG00000027668. DR GeneID; 67414; -. DR KEGG; mmu:67414; -. DR UCSC; uc008owi.2; mouse. DR CTD; 55669; -. DR MGI; MGI:1914664; Mfn1. DR eggNOG; COG0699; -. DR GeneTree; ENSGT00390000013727; -. DR HOVERGEN; HBG052465; -. DR InParanoid; Q811U4; -. DR KO; K06030; -. DR OMA; AMTDEIC; -. DR OrthoDB; EOG7HB58M; -. DR TreeFam; TF314289; -. DR ChiTaRS; Mfn1; mouse. DR EvolutionaryTrace; Q811U4; -. DR NextBio; 324498; -. DR PRO; PR:Q811U4; -. DR Proteomes; UP000000589; Chromosome 3. DR Bgee; Q811U4; -. DR CleanEx; MM_MFN1; -. DR ExpressionAtlas; Q811U4; baseline and differential. DR Genevisible; Q811U4; MM. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; IEA:InterPro. DR GO; GO:0008053; P:mitochondrial fusion; IMP:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.300; -; 2. 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; PF04799; Fzo_mitofusin; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS51718; G_DYNAMIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Complete proteome; Developmental protein; KW GTP-binding; Hydrolase; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Nucleotide-binding; Reference proteome; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT CHAIN 1 741 Mitofusin-1. FT /FTId=PRO_0000127673. FT TOPO_DOM 1 584 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 585 605 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 606 608 Mitochondrial intermembrane. FT {ECO:0000255}. FT TRANSMEM 609 629 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 630 741 Cytoplasmic. {ECO:0000255}. FT DOMAIN 72 321 Dynamin-type G. FT NP_BIND 82 89 GTP. {ECO:0000305}. FT NP_BIND 178 182 GTP. {ECO:0000305}. FT NP_BIND 237 240 GTP. {ECO:0000305}. FT COILED 371 408 {ECO:0000269|PubMed:15297672}. FT COILED 677 735 {ECO:0000269|PubMed:15297672}. FT CONFLICT 209 209 E -> G (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 328 329 IS -> VL (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 335 335 T -> A (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 521 521 V -> A (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 588 588 L -> W (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 619 619 L -> S (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 718 718 K -> R (in Ref. 2; BAB31111). FT {ECO:0000305}. FT CONFLICT 720 720 V -> I (in Ref. 3; AAH02133/AAH56641). FT {ECO:0000305}. FT HELIX 676 733 {ECO:0000244|PDB:1T3J}. SQ SEQUENCE 741 AA; 83726 MW; 36E5E90DB0C0D5A1 CRC64; MAETVSPLKH FVLAKKAITA IFGQLLEFVT EGSHFVEATY RNPELDRIAS EDDLVEIQGY RNKLAVIGEV LSRRHMKVAF FGRTSSGKSS VINAMLWDKV LPSGIGHTTN CFLSVEGTDG DKAYLMTEGS DEKKSVKTVN QLAHALHMDK DLKAGCLVHV FWPKAKCALL RDDLVLVDSP GTDVTTELDI WIDKFCLDAD VFVLVANSES TLMNTEKHFF HKVNERLSKP NIFILNNRWD ASASEPEYME DVRRQHMERC LHFLVEELKV VSPSEARNRI FFVSAKEVLN SRKHKAQGMP EGGGALAEGF QARLQEFQNF EQTFEECISQ SAVKTKFEQH TIRAKQILDT VKNILDSVNV AAAEKRVYSM EEREDQIDRL DFIRNQMNLL TLDVKKKIKE VTEEVANKVS CAMTDEICRL SVLVDEFCSE FHPTPSVLKV YKSELNKHIE DGMGRNLADR CTNEVNASIL QSQQEIIENL KPLLPAGIQN KLHTLIPCKK FDLSYDLNCH KLCSDFQEDI VFRFSLGWSS LVHRFLGSTN AQRVLLGLSE PIFQVPRSLA STPTAPSNPA APDNAAQEEL MITLITGLAS LTSRTSMGII VVGGVIWKTV GWKLISVTLS MYGALYLYER LTWTTRAKER AFKQQFVNYA TEKLQMIVSF TSANCSHQVQ QEMATTFARL CQQVDVTQKH LEEEIARLSK EIDQLEKIQN NSKLLRNKAV QLESELENFS KQFLHPSSGE S //