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Q8IWA4 (MFN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitofusin-1

EC=3.6.5.-
Alternative name(s):
Fzo homolog
Transmembrane GTPase MFN1
Gene names
Name:MFN1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length741 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN1 acts independently of the cytoskeleton. Overexpression induces the formation of mitochondrial networks. Ref.1 Ref.10 Ref.11 Ref.14

Catalytic activity

GTP + H2O = GDP + phosphate.

Subunit structure

Forms homomultimers and heteromultimers with MFN2. Multimerization, which is mediated by the second coiled coil region, may play an essential role in mitochondrion fusion By similarity. Participates in a high molecular weight multiprotein complex. Interacts with VAT1 By similarity.

Subcellular location

Mitochondrion outer membrane; Multi-pass membrane protein Probable Ref.8 Ref.11.

Isoform 2: Cytoplasm Ref.8 Ref.11.

Tissue specificity

Ubiquitous. Expressed at slightly higher level in kidney and heart. Isoform 2 may be overexpressed in some tumors, such as lung cancers. Ref.8 Ref.9 Ref.11

Post-translational modification

Ubiquitinated by MARCH5. When mitochondria are depolarized and dysfunctional, it is ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that contains FBXO7 and PARK2. Ref.12 Ref.15

Sequence similarities

Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.

Contains 1 dynamin-type G (guanine nucleotide-binding) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAVSQ7Z4342EBI-1048197,EBI-995373

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IWA4-1)

Also known as: TG741;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8IWA4-2)

Also known as: TG370;

The sequence of this isoform differs from the canonical sequence as follows:
     367-370: HYSV → FHVQ
     371-741: Missing.
Isoform 3 (identifier: Q8IWA4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     444-554: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 741741Mitofusin-1
PRO_0000127672

Regions

Topological domain1 – 584584Cytoplasmic Potential
Transmembrane585 – 60521Helical; Name=1; Potential
Topological domain606 – 6083Mitochondrial intermembrane Potential
Transmembrane609 – 62921Helical; Name=2; Potential
Topological domain630 – 741112Cytoplasmic Potential
Domain72 – 321250Dynamin-type G
Nucleotide binding82 – 898GTP Probable
Nucleotide binding178 – 1825GTP Probable
Nucleotide binding237 – 2404GTP Probable
Coiled coil371 – 40838 Potential
Coiled coil679 – 73456 Potential

Natural variations

Alternative sequence367 – 3704HYSV → FHVQ in isoform 2.
VSP_010362
Alternative sequence371 – 741371Missing in isoform 2.
VSP_010363
Alternative sequence444 – 554111Missing in isoform 3.
VSP_010364
Natural variant4151D → H in a colorectal cancer sample; somatic mutation. Ref.16
VAR_036115
Natural variant5231P → R. Ref.1 Ref.2 Ref.4 Ref.5 Ref.7
Corresponds to variant rs7637065 [ dbSNP | Ensembl ].
VAR_018606

Experimental info

Mutagenesis881K → T: Induces a strong decrease in mitochondrial clustering. Ref.11
Mutagenesis1091T → A: Acts as a dominant negative mutant; induces fragmentation of mitochondria. Ref.11
Sequence conflict171A → G in AAK06840. Ref.1
Sequence conflict211I → V in BAA91327. Ref.2
Sequence conflict1621W → C in AAB64220. Ref.6
Sequence conflict2261R → W in AAK06840. Ref.1
Sequence conflict2711V → A in AAK06840. Ref.1
Sequence conflict4061A → P in AAB64220. Ref.6
Sequence conflict6881Q → H in AAB64220. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TG741) [UniParc].

Last modified June 26, 2007. Version 2.
Checksum: C4C1F56561D44A79

FASTA74184,100
        10         20         30         40         50         60 
MAEPVSPLKH FVLAKKAITA IFDQLLEFVT EGSHFVEATY KNPELDRIAT EDDLVEMQGY 

        70         80         90        100        110        120 
KDKLSIIGEV LSRRHMKVAF FGRTSSGKSS VINAMLWDKV LPSGIGHITN CFLSVEGTDG 

       130        140        150        160        170        180 
DKAYLMTEGS DEKKSVKTVN QLAHALHMDK DLKAGCLVRV FWPKAKCALL RDDLVLVDSP 

       190        200        210        220        230        240 
GTDVTTELDS WIDKFCLDAD VFVLVANSES TLMNTEKHFF HKVNERLSKP NIFILNNRWD 

       250        260        270        280        290        300 
ASASEPEYME DVRRQHMERC LHFLVEELKV VNALEAQNRI FFVSAKEVLS ARKQKAQGMP 

       310        320        330        340        350        360 
ESGVALAEGF HARLQEFQNF EQIFEECISQ SAVKTKFEQH TIRAKQILAT VKNIMDSVNL 

       370        380        390        400        410        420 
AAEDKRHYSV EEREDQIDRL DFIRNQMNLL TLDVKKKIKE VTEEVANKVS CAMTDEICRL 

       430        440        450        460        470        480 
SVLVDEFCSE FHPNPDVLKI YKSELNKHIE DGMGRNLADR CTDEVNALVL QTQQEIIENL 

       490        500        510        520        530        540 
KPLLPAGIQD KLHTLIPCKK FDLSYNLNYH KLCSDFQEDI VFPFSLGWSS LVHRFLGPRN 

       550        560        570        580        590        600 
AQRVLLGLSE PIFQLPRSLA STPTAPTTPA TPDNASQEEL MITLVTGLAS VTSRTSMGII 

       610        620        630        640        650        660 
IVGGVIWKTI GWKLLSVSLT MYGALYLYER LSWTTHAKER AFKQQFVNYA TEKLRMIVSS 

       670        680        690        700        710        720 
TSANCSHQVK QQIATTFARL CQQVDITQKQ LEEEIARLPK EIDQLEKIQN NSKLLRNKAV 

       730        740 
QLENELENFT KQFLPSSNEE S 

« Hide

Isoform 2 (TG370) [UniParc].

Checksum: 187B06EA1E971C6E
Show »

FASTA37041,883
Isoform 3 [UniParc].

Checksum: D173A310365208BD
Show »

FASTA63071,401

References

« Hide 'large scale' references
[1]"Control of mitochondrial morphology by a human mitofusin."
Santel A., Fuller M.T.
J. Cell Sci. 114:867-874(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANT ARG-523.
Tissue: Heart.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ARG-523.
Tissue: Ileal mucosa and Trachea.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-523.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-523.
Tissue: Testis.
[6]"Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase."
Hales K.G., Fuller M.T.
Cell 90:121-129(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 138-741 (ISOFORM 3).
Tissue: Brain.
[7]Yu W., Gibbs R.A.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 374-741, VARIANT ARG-523.
Tissue: Brain.
[8]"Novel transmembrane GTPase of non-small cell lung cancer identified by mRNA differential display."
Chung J.-G., Yeh K.-T., Wu S.-L., Hsu N.-Y., Chen G.-W., Yeh Y.-W., Ho H.-C.
Cancer Res. 61:8873-8879(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo."
Rojo M., Legros F., Chateau D., Lombes A.
J. Cell Sci. 115:1663-1674(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins."
Legros F., Lombes A., Frachon P., Rojo M.
Mol. Biol. Cell 13:4343-4354(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells."
Santel A., Frank S., Gaume B., Herrler M., Youle R.J., Fuller M.T.
J. Cell Sci. 116:2763-2774(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-88 AND THR-109.
[12]"Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1."
Park Y.Y., Lee S., Karbowski M., Neutzner A., Youle R.J., Cho H.
J. Cell Sci. 123:619-626(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY MARCH5.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission."
Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D., Ryan M.T.
J. Biol. Chem. 288:27584-27593(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy."
Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., Plun-Favreau H.
Nat. Neurosci. 16:1257-1265(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[16]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-415.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF329637 mRNA. Translation: AAK06840.1.
AK000700 mRNA. Translation: BAA91327.1.
AK314306 mRNA. Translation: BAG36958.1.
AC007823 Genomic DNA. No translation available.
AC007620 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78406.1.
CH471052 Genomic DNA. Translation: EAW78410.1.
CH471052 Genomic DNA. Translation: EAW78411.1.
BC040557 mRNA. Translation: AAH40557.1.
U95822 mRNA. Translation: AAB64220.1.
AF054986 mRNA. Translation: AAC09347.1.
CCDSCCDS3228.1. [Q8IWA4-1]
RefSeqNP_284941.2. NM_033540.2.
XP_005247653.2. XM_005247596.2.
UniGeneHs.478383.

3D structure databases

ProteinModelPortalQ8IWA4.
SMRQ8IWA4. Positions 674-734.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120801. 7 interactions.
DIPDIP-50289N.
IntActQ8IWA4. 4 interactions.
MINTMINT-6940236.
STRING9606.ENSP00000263969.

Protein family/group databases

TCDB9.B.25.2.1. the mitochondrial inner/outer membrane fusion (mmf) family.

PTM databases

PhosphoSiteQ8IWA4.

Polymorphism databases

DMDM150421594.

Proteomic databases

MaxQBQ8IWA4.
PaxDbQ8IWA4.
PRIDEQ8IWA4.

Protocols and materials databases

DNASU55669.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263969; ENSP00000263969; ENSG00000171109. [Q8IWA4-1]
ENST00000280653; ENSP00000280653; ENSG00000171109. [Q8IWA4-3]
ENST00000357390; ENSP00000349963; ENSG00000171109. [Q8IWA4-2]
ENST00000471841; ENSP00000420617; ENSG00000171109. [Q8IWA4-1]
GeneID55669.
KEGGhsa:55669.
UCSCuc003fjs.3. human. [Q8IWA4-1]

Organism-specific databases

CTD55669.
GeneCardsGC03P179065.
HGNCHGNC:18262. MFN1.
HPACAB033437.
MIM608506. gene.
neXtProtNX_Q8IWA4.
PharmGKBPA134945973.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0699.
HOVERGENHBG052465.
InParanoidQ8IWA4.
KOK06030.
OMAAMTDEIC.
OrthoDBEOG7HB58M.
PhylomeDBQ8IWA4.
TreeFamTF314289.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ8IWA4.
BgeeQ8IWA4.
CleanExHS_MFN1.
GenevestigatorQ8IWA4.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR001401. Dynamin_GTPase.
IPR006884. Fzo/mitofusin_HR2.
IPR027088. Mitofusin-1.
IPR027094. Mitofusin_fam.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10465. PTHR10465. 1 hit.
PTHR10465:SF2. PTHR10465:SF2. 1 hit.
PfamPF00350. Dynamin_N. 1 hit.
PF04799. Fzo_mitofusin. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS51718. G_DYNAMIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMFN1.
GenomeRNAi55669.
NextBio60436.
PROQ8IWA4.
SOURCESearch...

Entry information

Entry nameMFN1_HUMAN
AccessionPrimary (citable) accession number: Q8IWA4
Secondary accession number(s): B2RAR1 expand/collapse secondary AC list , D3DNR6, O15323, O60639, Q9BZB5, Q9NWQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: June 26, 2007
Last modified: July 9, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM