MFN1_HUMAN
ID MFN1_HUMAN Reviewed; 741 AA.
AC Q8IWA4; A0A0C4DFN1; B2RAR1; D3DNR6; O15323; O60639; Q9BZB5; Q9NWQ2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Mitofusin-1;
DE EC=3.6.5.- {ECO:0000269|PubMed:27920125, ECO:0000269|PubMed:28114303};
DE AltName: Full=Fzo homolog {ECO:0000303|PubMed:11950885};
DE AltName: Full=Transmembrane GTPase MFN1;
GN Name=MFN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=11181170; DOI=10.1242/jcs.114.5.867;
RA Santel A., Fuller M.T.;
RT "Control of mitochondrial morphology by a human mitofusin.";
RL J. Cell Sci. 114:867-874(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ileal mucosa, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 138-741 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=9230308; DOI=10.1016/s0092-8674(00)80319-0;
RA Hales K.G., Fuller M.T.;
RT "Developmentally regulated mitochondrial fusion mediated by a conserved,
RT novel, predicted GTPase.";
RL Cell 90:121-129(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 374-741.
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP SUBCELLULAR LOCATION (ISOFORM 2), TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RX PubMed=11751411;
RA Chung J.-G., Yeh K.-T., Wu S.-L., Hsu N.-Y., Chen G.-W., Yeh Y.-W.,
RA Ho H.-C.;
RT "Novel transmembrane GTPase of non-small cell lung cancer identified by
RT mRNA differential display.";
RL Cancer Res. 61:8873-8879(2001).
RN [9]
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 [10]
RP FUNCTION.
RX PubMed=12475957; DOI=10.1091/mbc.e02-06-0330;
RA Legros F., Lombes A., Frachon P., Rojo M.;
RT "Mitochondrial fusion in human cells is efficient, requires the inner
RT membrane potential, and is mediated by mitofusins.";
RL Mol. Biol. Cell 13:4343-4354(2002).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF LYS-88 AND THR-109.
RX PubMed=12759376; DOI=10.1242/jcs.00479;
RA Santel A., Frank S., Gaume B., Herrler M., Youle R.J., Fuller M.T.;
RT "Mitofusin-1 protein is a generally expressed mediator of mitochondrial
RT fusion in mammalian cells.";
RL J. Cell Sci. 116:2763-2774(2003).
RN [12]
RP UBIQUITINATION BY MARCHF5.
RX PubMed=20103533; DOI=10.1242/jcs.061481;
RA Park Y.Y., Lee S., Karbowski M., Neutzner A., Youle R.J., Cho H.;
RT "Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular
RT senescence through dynamin-related protein 1 and mitofusin 1.";
RL J. Cell Sci. 123:619-626(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP UBIQUITINATION.
RX PubMed=23933751; DOI=10.1038/nn.3489;
RA Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M.,
RA Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H.,
RA Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H.,
RA Plun-Favreau H.;
RT "The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to
RT mediate mitophagy.";
RL Nat. Neurosci. 16:1257-1265(2013).
RN [15]
RP INTERACTION WITH THG1L.
RX PubMed=25008184; DOI=10.2337/db13-1256;
RA Hickey F.B., Corcoran J.B., Griffin B., Bhreathnach U., Mortiboys H.,
RA Reid H.M., Andrews D., Byrne S., Furlong F., Martin F., Godson C.,
RA Murphy M.;
RT "IHG-1 increases mitochondrial fusion and bioenergetic function.";
RL Diabetes 63:4314-4325(2014).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-364 AND 696-741 IN COMPLEXES
RP WITH GDP AND GTP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR
RP LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-15; LYS-88; PRO-102; ASP-173;
RP ILE-328; LYS-336; LEU-705 AND PHE-733.
RX PubMed=27920125; DOI=10.1083/jcb.201609019;
RA Qi Y., Yan L., Yu C., Guo X., Zhou X., Hu X., Huang X., Rao Z., Lou Z.,
RA Hu J.;
RT "Structures of human mitofusin 1 provide insight into mitochondrial
RT tethering.";
RL J. Cell Biol. 215:621-629(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-364 AND 696-741 IN COMPLEXES
RP WITH GDP; GTP AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN,
RP AND MUTAGENESIS OF LYS-15; ARG-74; LYS-99; HIS-107; HIS-144; ASP-189;
RP GLU-209; ARG-238; TRP-239; GLY-309; LYS-336 AND LEU-705.
RX PubMed=28114303; DOI=10.1038/nature21077;
RA Cao Y.L., Meng S., Chen Y., Feng J.X., Gu D.D., Yu B., Li Y.J., Yang J.Y.,
RA Liao S., Chan D.C., Gao S.;
RT "MFN1 structures reveal nucleotide-triggered dimerization critical for
RT mitochondrial fusion.";
RL Nature 542:372-376(2017).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-415.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Mitochondrial outer membrane GTPase that mediates
CC mitochondrial clustering and fusion (PubMed:12475957, PubMed:12759376,
CC PubMed:27920125, PubMed:28114303). Membrane clustering requires GTPase
CC activity (PubMed:27920125). It may involve a major rearrangement of the
CC coiled coil domains (PubMed:27920125, PubMed:28114303). Mitochondria
CC are highly dynamic organelles, and their morphology is determined by
CC the equilibrium between mitochondrial fusion and fission events
CC (PubMed:12475957, PubMed:12759376). Overexpression induces the
CC formation of mitochondrial networks (in vitro) (PubMed:12759376). Has
CC low GTPase activity (PubMed:27920125, PubMed:28114303).
CC {ECO:0000269|PubMed:12475957, ECO:0000269|PubMed:12759376,
CC ECO:0000269|PubMed:27920125, ECO:0000269|PubMed:28114303}.
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:0000269|PubMed:27920125, ECO:0000269|PubMed:28114303};
CC -!- SUBUNIT: Homodimer, also in the absence of bound GTP (PubMed:27920125,
CC PubMed:28114303). Forms higher oligomers in the presence of a
CC transition state GTP analog (PubMed:28114303). Forms homomultimers and
CC heteromultimers with MFN2 (By similarity). Oligomerization is essential
CC for mitochondrion fusion (PubMed:27920125, PubMed:28114303). Component
CC of a high molecular weight multiprotein complex (PubMed:12759376).
CC Interacts with VAT1 (By similarity). Interacts with THG1L; THG1L
CC probably functions as a guanyl-nucleotide exchange factor/GEF,
CC activating MFN1. {ECO:0000250|UniProtKB:Q811U4,
CC ECO:0000250|UniProtKB:Q8R4Z9, ECO:0000269|PubMed:12759376,
CC ECO:0000269|PubMed:25008184, ECO:0000269|PubMed:27920125}.
CC -!- INTERACTION:
CC Q8IWA4; Q7Z434: MAVS; NbExp=2; IntAct=EBI-1048197, EBI-995373;
CC Q8IWA4; Q8IWA4: MFN1; NbExp=13; IntAct=EBI-1048197, EBI-1048197;
CC Q8IWA4; O95140: MFN2; NbExp=2; IntAct=EBI-1048197, EBI-3324756;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:12759376, ECO:0000305|PubMed:27920125}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:12759376}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:11751411}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=TG741 {ECO:0000303|PubMed:11751411};
CC IsoId=Q8IWA4-1; Sequence=Displayed;
CC Name=2; Synonyms=TG370 {ECO:0000303|PubMed:11751411};
CC IsoId=Q8IWA4-2; Sequence=VSP_010362, VSP_010363;
CC Name=3;
CC IsoId=Q8IWA4-3; Sequence=VSP_010364;
CC -!- TISSUE SPECIFICITY: Detected in kidney and heart (at protein level)
CC (PubMed:12759376). Ubiquitous (PubMed:11950885, PubMed:12759376).
CC Expressed at slightly higher level in kidney and heart
CC (PubMed:12759376). Isoform 2 may be overexpressed in some tumors, such
CC as lung cancers (PubMed:11751411). {ECO:0000269|PubMed:11751411,
CC ECO:0000269|PubMed:11950885, ECO:0000269|PubMed:12759376}.
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:0000269|PubMed:27920125,
CC ECO:0000269|PubMed:28114303}.
CC -!- PTM: Ubiquitinated by non-degradative ubiquitin by PRKN
CC (PubMed:23933751). Deubiquitination by USP30 inhibits mitochondrial
CC fusion (By similarity). Ubiquitinated by MARCHF5 (PubMed:20103533).
CC When mitochondria are depolarized and dysfunctional, it is
CC ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein
CC ligase complex that contains FBXO7 and PRKN (PubMed:23933751).
CC {ECO:0000250|UniProtKB:Q811U4, ECO:0000269|PubMed:20103533,
CC ECO:0000269|PubMed:23933751}.
CC -!- MISCELLANEOUS: A truncated MFN1 construct containing the GTPase domain
CC and the associated helix bundle is a monomer in the absence of bound
CC GTP and a homodimer in the GTP-bound form; GDP cannot replace GTP and
CC induce dimerization. {ECO:0000269|PubMed:27920125,
CC ECO:0000269|PubMed:28114303}.
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; AF329637; AAK06840.1; -; mRNA.
DR EMBL; AK000700; BAA91327.1; -; mRNA.
DR EMBL; AK314306; BAG36958.1; -; mRNA.
DR EMBL; AC007823; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007620; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF457722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78406.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78410.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78411.1; -; Genomic_DNA.
DR EMBL; BC040557; AAH40557.1; -; mRNA.
DR EMBL; U95822; AAB64220.1; -; mRNA.
DR EMBL; AF054986; AAC09347.1; -; mRNA.
DR CCDS; CCDS3228.1; -. [Q8IWA4-1]
DR RefSeq; NP_284941.2; NM_033540.2. [Q8IWA4-1]
DR RefSeq; XP_005247653.2; XM_005247596.3. [Q8IWA4-1]
DR PDB; 5GNR; X-ray; 2.65 A; A=1-364, A=696-741.
DR PDB; 5GNS; X-ray; 2.70 A; A=1-364, A=696-741.
DR PDB; 5GNT; X-ray; 2.67 A; A=1-364, A=696-741.
DR PDB; 5GNU; X-ray; 4.11 A; A=1-364, A=696-741.
DR PDB; 5GO4; X-ray; 2.20 A; A=1-365, A=696-741.
DR PDB; 5GOE; X-ray; 1.80 A; A=1-369, A=696-741.
DR PDB; 5GOF; X-ray; 1.60 A; A=1-362, A=696-741.
DR PDB; 5GOM; X-ray; 2.80 A; A/B=1-362, A/B=696-741.
DR PDB; 5YEW; X-ray; 3.20 A; A/B/C=1-364, A/B/C=694-741.
DR PDBsum; 5GNR; -.
DR PDBsum; 5GNS; -.
DR PDBsum; 5GNT; -.
DR PDBsum; 5GNU; -.
DR PDBsum; 5GO4; -.
DR PDBsum; 5GOE; -.
DR PDBsum; 5GOF; -.
DR PDBsum; 5GOM; -.
DR PDBsum; 5YEW; -.
DR AlphaFoldDB; Q8IWA4; -.
DR SMR; Q8IWA4; -.
DR BioGRID; 120801; 47.
DR DIP; DIP-50289N; -.
DR IntAct; Q8IWA4; 10.
DR MINT; Q8IWA4; -.
DR STRING; 9606.ENSP00000420617; -.
DR TCDB; 1.N.6.1.2; the mitochondrial inner/outer membrane fusion (mmf) family.
DR iPTMnet; Q8IWA4; -.
DR PhosphoSitePlus; Q8IWA4; -.
DR BioMuta; MFN1; -.
DR DMDM; 150421594; -.
DR EPD; Q8IWA4; -.
DR jPOST; Q8IWA4; -.
DR MassIVE; Q8IWA4; -.
DR MaxQB; Q8IWA4; -.
DR PaxDb; Q8IWA4; -.
DR PeptideAtlas; Q8IWA4; -.
DR PRIDE; Q8IWA4; -.
DR ProteomicsDB; 70826; -. [Q8IWA4-1]
DR ProteomicsDB; 70827; -. [Q8IWA4-2]
DR ProteomicsDB; 70828; -. [Q8IWA4-3]
DR Antibodypedia; 33743; 536 antibodies from 40 providers.
DR DNASU; 55669; -.
DR Ensembl; ENST00000263969.9; ENSP00000263969.5; ENSG00000171109.19. [Q8IWA4-1]
DR Ensembl; ENST00000357390.8; ENSP00000349963.4; ENSG00000171109.19. [Q8IWA4-2]
DR Ensembl; ENST00000471841.6; ENSP00000420617.1; ENSG00000171109.19. [Q8IWA4-1]
DR GeneID; 55669; -.
DR KEGG; hsa:55669; -.
DR MANE-Select; ENST00000471841.6; ENSP00000420617.1; NM_033540.3; NP_284941.2.
DR UCSC; uc003fjs.4; human. [Q8IWA4-1]
DR CTD; 55669; -.
DR DisGeNET; 55669; -.
DR GeneCards; MFN1; -.
DR HGNC; HGNC:18262; MFN1.
DR HPA; ENSG00000171109; Low tissue specificity.
DR MIM; 608506; gene.
DR neXtProt; NX_Q8IWA4; -.
DR OpenTargets; ENSG00000171109; -.
DR PharmGKB; PA134945973; -.
DR VEuPathDB; HostDB:ENSG00000171109; -.
DR eggNOG; KOG0448; Eukaryota.
DR GeneTree; ENSGT00390000013727; -.
DR HOGENOM; CLU_792918_0_0_1; -.
DR InParanoid; Q8IWA4; -.
DR OMA; HMERCLN; -.
DR OrthoDB; 216494at2759; -.
DR PhylomeDB; Q8IWA4; -.
DR TreeFam; TF314289; -.
DR PathwayCommons; Q8IWA4; -.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-HSA-9013419; RHOT2 GTPase cycle.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q8IWA4; -.
DR BioGRID-ORCS; 55669; 28 hits in 1072 CRISPR screens.
DR ChiTaRS; MFN1; human.
DR GeneWiki; MFN1; -.
DR GenomeRNAi; 55669; -.
DR Pharos; Q8IWA4; Tbio.
DR PRO; PR:Q8IWA4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IWA4; protein.
DR Bgee; ENSG00000171109; Expressed in secondary oocyte and 203 other tissues.
DR ExpressionAtlas; Q8IWA4; baseline and differential.
DR Genevisible; Q8IWA4; HS.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0031306; C:intrinsic component of mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0098799; C:outer mitochondrial membrane protein complex; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046039; P:GTP metabolic process; IDA:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; IDA:BHF-UCL.
DR GO; GO:0051646; P:mitochondrion localization; IMP:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IEA:Ensembl.
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 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; GTP-binding;
KW Hydrolase; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..741
FT /note="Mitofusin-1"
FT /id="PRO_0000127672"
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:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:28114303"
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:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:28114303"
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:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:28114303"
FT COILED 371..408
FT /evidence="ECO:0000255"
FT COILED 679..734
FT /evidence="ECO:0000255"
FT BINDING 85..90
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0000269|PubMed:28114303, ECO:0007744|PDB:5GNR,
FT ECO:0007744|PDB:5GNS, ECO:0007744|PDB:5GOE,
FT ECO:0007744|PDB:5GOF"
FT BINDING 237..240
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0000269|PubMed:28114303, ECO:0007744|PDB:5GNS,
FT ECO:0007744|PDB:5GOE, ECO:0007744|PDB:5GOF"
FT BINDING 284
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0000269|PubMed:28114303, ECO:0007744|PDB:5GNR,
FT ECO:0007744|PDB:5GOE, ECO:0007744|PDB:5GOF"
FT BINDING 286
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0007744|PDB:5GNS"
FT VAR_SEQ 367..370
FT /note="HYSV -> FHVQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_010362"
FT VAR_SEQ 371..741
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_010363"
FT VAR_SEQ 444..554
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9230308"
FT /id="VSP_010364"
FT VARIANT 415
FT /note="D -> H (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036115"
FT VARIANT 523
FT /note="R -> P (in dbSNP:rs7637065)"
FT /id="VAR_018606"
FT MUTAGEN 15
FT /note="K->A: Decreases GTPase activity. Impairs
FT mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0000269|PubMed:28114303"
FT MUTAGEN 74
FT /note="R->P: Mildly decreases GTPase activity and impairs
FT mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 88
FT /note="K->A: Abolishes GTPase activity. Abolishes
FT dimerization."
FT /evidence="ECO:0000269|PubMed:27920125"
FT MUTAGEN 88
FT /note="K->T: Induces a strong decrease in mitochondrial
FT clustering."
FT /evidence="ECO:0000269|PubMed:12759376"
FT MUTAGEN 99
FT /note="K->A: Mildly decreases GTPase activity."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 102
FT /note="P->L: Impairs protein folding. Decreases GTPase
FT activity."
FT /evidence="ECO:0000269|PubMed:27920125"
FT MUTAGEN 107
FT /note="H->A: Loss of function in mitochondrial fusion.
FT Abolishes GTPase activity, but has no effect on GTP
FT binding."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 109
FT /note="T->A: Acts as a dominant negative mutant; induces
FT fragmentation of mitochondria."
FT /evidence="ECO:0000269|PubMed:12759376"
FT MUTAGEN 144
FT /note="H->A: Abolishes GTPase activity. Abolishes
FT dimerization."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 173
FT /note="D->A: Decreases GTPase activity."
FT /evidence="ECO:0000269|PubMed:27920125"
FT MUTAGEN 189
FT /note="D->A: Causes mitochondrial clumping."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 209
FT /note="E->A: Abolishes dimerization. Loss of function in
FT mitochondrial fusion. Abolishes GTPase activity, but has no
FT effect on GTP binding."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 238
FT /note="R->A: Abolishes dimerization. Loss of function in
FT mitochondrial fusion. Abolishes GTPase activity, but has no
FT effect on GTP binding."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 239
FT /note="W->A: Abolishes GTP binding and GTPase activity.
FT Loss of function in mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 245
FT /note="E->A: Decreases GTPase activity. Abolishes
FT dimerization. Impairs mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 309
FT /note="G->P: Mildly decreases GTPase activity and impairs
FT mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 328
FT /note="I->A: Slightly decreases GTPase activity."
FT /evidence="ECO:0000269|PubMed:27920125"
FT MUTAGEN 336
FT /note="K->N: Loss of function in mitochondrial fusion.
FT Abolishes dimerization. Decreases GTPase activity."
FT /evidence="ECO:0000269|PubMed:27920125"
FT MUTAGEN 336
FT /note="K->P: Decreases GTPase activity and impairs
FT mitochondrial fusion."
FT /evidence="ECO:0000269|PubMed:28114303"
FT MUTAGEN 705
FT /note="L->P: Impairs protein folding. Decreases GTPase
FT activity."
FT /evidence="ECO:0000269|PubMed:27920125,
FT ECO:0000269|PubMed:28114303"
FT MUTAGEN 733
FT /note="F->P: Impairs protein folding."
FT /evidence="ECO:0000269|PubMed:27920125"
FT CONFLICT 17
FT /note="A -> G (in Ref. 1; AAK06840)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="I -> V (in Ref. 2; BAA91327)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="W -> C (in Ref. 6; AAB64220)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="R -> W (in Ref. 1; AAK06840)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="V -> A (in Ref. 1; AAK06840)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="A -> P (in Ref. 6; AAB64220)"
FT /evidence="ECO:0000305"
FT CONFLICT 688
FT /note="Q -> H (in Ref. 6; AAB64220)"
FT /evidence="ECO:0000305"
FT HELIX 9..41
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:5GO4"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 51..72
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:5GO4"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:5GOE"
FT STRAND 112..122
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:5GOF"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:5YEW"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:5GOE"
FT HELIX 189..195
FT /evidence="ECO:0007829|PDB:5GOF"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 200..207
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 214..226
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 239..242
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 246..265
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:5GOF"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 285..292
FT /evidence="ECO:0007829|PDB:5GOF"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:5GNR"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:5GO4"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5GNR"
FT HELIX 310..362
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 374..390
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 395..407
FT /evidence="ECO:0007829|PDB:5GOF"
FT HELIX 410..431
FT /evidence="ECO:0007829|PDB:5GO4"
SQ SEQUENCE 741 AA; 84160 MW; B7BDC22437E30A58 CRC64;
MAEPVSPLKH FVLAKKAITA IFDQLLEFVT EGSHFVEATY KNPELDRIAT EDDLVEMQGY
KDKLSIIGEV LSRRHMKVAF FGRTSSGKSS VINAMLWDKV LPSGIGHITN CFLSVEGTDG
DKAYLMTEGS DEKKSVKTVN QLAHALHMDK DLKAGCLVRV FWPKAKCALL RDDLVLVDSP
GTDVTTELDS WIDKFCLDAD VFVLVANSES TLMNTEKHFF HKVNERLSKP NIFILNNRWD
ASASEPEYME DVRRQHMERC LHFLVEELKV VNALEAQNRI FFVSAKEVLS ARKQKAQGMP
ESGVALAEGF HARLQEFQNF EQIFEECISQ SAVKTKFEQH TIRAKQILAT VKNIMDSVNL
AAEDKRHYSV EEREDQIDRL DFIRNQMNLL TLDVKKKIKE VTEEVANKVS CAMTDEICRL
SVLVDEFCSE FHPNPDVLKI YKSELNKHIE DGMGRNLADR CTDEVNALVL QTQQEIIENL
KPLLPAGIQD KLHTLIPCKK FDLSYNLNYH KLCSDFQEDI VFRFSLGWSS LVHRFLGPRN
AQRVLLGLSE PIFQLPRSLA STPTAPTTPA TPDNASQEEL MITLVTGLAS VTSRTSMGII
IVGGVIWKTI GWKLLSVSLT MYGALYLYER LSWTTHAKER AFKQQFVNYA TEKLRMIVSS
TSANCSHQVK QQIATTFARL CQQVDITQKQ LEEEIARLPK EIDQLEKIQN NSKLLRNKAV
QLENELENFT KQFLPSSNEE S
