Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O95140

- MFN2_HUMAN

UniProt

O95140 - MFN2_HUMAN

Protein

Mitofusin-2

Gene

MFN2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 3 (24 May 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    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. MFN2 acts independently of the cytoskeleton. It therefore plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. Overexpression induces the formation of mitochondrial networks. Plays an important role in the regulation of vascular smooth muscle cell proliferation. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PARK2 recruitment to dysfunctional mitochondria. Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress. Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions.5 Publications

    Catalytic activityi

    GTP + H2O = GDP + phosphate.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi103 – 1108GTPCurated
    Nucleotide bindingi199 – 2035GTPCurated
    Nucleotide bindingi258 – 2614GTPCurated

    GO - Molecular functioni

    1. GTPase activity Source: InterPro
    2. GTP binding Source: UniProtKB-KW
    3. protein binding Source: UniProtKB
    4. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. blastocyst formation Source: Ensembl
    2. blood coagulation Source: Reactome
    3. camera-type eye morphogenesis Source: Ensembl
    4. cell death Source: UniProtKB-KW
    5. mitochondrial fusion Source: UniProtKB
    6. mitochondrial membrane organization Source: UniProtKB
    7. mitochondrion localization Source: UniProtKB
    8. negative regulation of Ras protein signal transduction Source: UniProtKB
    9. negative regulation of smooth muscle cell proliferation Source: UniProtKB
    10. protein targeting to mitochondrion Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Apoptosis, Autophagy, Unfolded protein response

    Keywords - Ligandi

    GTP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_24970. Factors involved in megakaryocyte development and platelet production.

    Protein family/group databases

    TCDBi9.B.25.2.1. the mitochondrial inner/outer membrane fusion (mmf) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitofusin-2 (EC:3.6.5.-)
    Alternative name(s):
    Transmembrane GTPase MFN2
    Gene namesi
    Name:MFN2
    Synonyms:CPRP1, KIAA0214
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:16877. MFN2.

    Subcellular locationi

    Mitochondrion outer membrane 4 Publications; Multi-pass membrane protein 4 Publications
    Note: Colocalizes with BAX during apoptosis.

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. integral component of membrane Source: UniProtKB-KW
    3. intrinsic component of mitochondrial outer membrane Source: UniProtKB
    4. microtubule cytoskeleton Source: Ensembl
    5. mitochondrial outer membrane Source: Reactome
    6. mitochondrion Source: UniProtKB

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion outer membrane

    Pathology & Biotechi

    Involvement in diseasei

    Charcot-Marie-Tooth disease 2A2 (CMT2A2) [MIM:609260]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti69 – 691V → F in CMT2A2; in a Turkish family. 1 Publication
    Corresponds to variant rs28940296 [ dbSNP | Ensembl ].
    VAR_018607
    Natural varianti76 – 761L → P in CMT2A2; in a European family. 1 Publication
    Corresponds to variant rs28940293 [ dbSNP | Ensembl ].
    VAR_018608
    Natural varianti94 – 941R → Q in CMT2A2; in a Japanese and Russian kindred. 1 Publication
    Corresponds to variant rs28940291 [ dbSNP | Ensembl ].
    VAR_018609
    Natural varianti233 – 2331L → V in CMT2A2. 1 Publication
    VAR_067088
    Natural varianti251 – 2511P → A in CMT2A2. 1 Publication
    Corresponds to variant rs28940295 [ dbSNP | Ensembl ].
    VAR_018610
    Natural varianti280 – 2801R → H in CMT2A2. 1 Publication
    Corresponds to variant rs28940294 [ dbSNP | Ensembl ].
    VAR_018611
    Natural varianti357 – 3571K → N in CMT2A2. 1 Publication
    VAR_022464
    Natural varianti364 – 3641R → W in CMT6 and CMT2A2. 2 Publications
    VAR_029880
    Natural varianti740 – 7401W → S in CMT2A2; in a European family. 1 Publication
    Corresponds to variant rs28940292 [ dbSNP | Ensembl ].
    VAR_018612
    Natural varianti744 – 7441E → M in CMT2A2; requires 2 nucleotide substitutions. 1 Publication
    VAR_067089
    Charcot-Marie-Tooth disease 6 (CMT6) [MIM:601152]: A form of Charcot-Marie-Tooth disease characterized by the association of axonal peripheral neuropathy with optic atrophy. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti94 – 941R → W in CMT6. 1 Publication
    VAR_029876
    Natural varianti206 – 2061T → I in CMT6. 1 Publication
    VAR_029877
    Natural varianti276 – 2761Q → R in CMT6. 1 Publication
    VAR_029878
    Natural varianti361 – 3611H → Y in CMT6. 1 Publication
    VAR_029879
    Natural varianti364 – 3641R → W in CMT6 and CMT2A2. 2 Publications
    VAR_029880

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi109 – 1091K → A or T: Does not affect its ability to cluster mitochondria; when overexpressed. 2 Publications
    Mutagenesisi110 – 1101S → N: Does not affect its ability to cluster mitochondria; when overexpressed. 1 Publication
    Mutagenesisi111 – 1111T → A: Diminishes interaction with PARK2 in presence of PINK1. Abolishes phosphorylation by PINK1 and interaction with PARK2 in presence of PINK1; when associated with ALA-442. 1 Publication
    Mutagenesisi111 – 1111T → E: Interacts with PARK2 in absence of PINK1; when associated with GLU-442. 1 Publication
    Mutagenesisi259 – 2591R → L: Does not affect its ability to cluster mitochondria; when overexpressed. 1 Publication
    Mutagenesisi442 – 4421S → A: Diminishes interaction with PARK2 in presence of PINK1. Abolishes phosphorylation by PINK1 and interaction with PARK2 in presence of PINK1; when associated with ALA-111. 1 Publication
    Mutagenesisi442 – 4421S → E: Interacts with PARK2 in absence of PINK1; when associated with GLU-111. 1 Publication
    Mutagenesisi622 – 6243GGV → AAL: Does not affect the targeting to mitochondrial outer membrane.
    Mutagenesisi622 – 6243GGV → RRE: Abolishes the targeting to mitochondrial outer membrane.
    Mutagenesisi657 – 6593KER → TGV: Does not affect the targeting to mitochondrial outer membrane.

    Keywords - Diseasei

    Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

    Organism-specific databases

    MIMi601152. phenotype.
    609260. phenotype.
    Orphaneti99947. Autosomal dominant Charcot-Marie-Tooth disease type 2A2.
    1215. Autosomal dominant optic atrophy plus syndrome.
    64751. Hereditary motor and sensory neuropathy type 5.
    90120. Hereditary motor and sensory neuropathy type 6.
    90118. Severe early-onset axonal neuropathy due to MFN2 deficiency.
    PharmGKBiPA134986046.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 757757Mitofusin-2PRO_0000127675Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei111 – 1111Phosphothreonine; by PINK11 Publication
    Modified residuei442 – 4421Phosphoserine; by PINK11 Publication

    Post-translational modificationi

    Phosphorylated by PINK1.1 Publication
    Ubiquitinated by non-degradative ubiquitin by PARK2, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO95140.
    PaxDbiO95140.
    PRIDEiO95140.

    PTM databases

    PhosphoSiteiO95140.

    Expressioni

    Tissue specificityi

    Ubiquitous; expressed at low level. Highly expressed in heart and kidney.2 Publications

    Gene expression databases

    ArrayExpressiO95140.
    BgeeiO95140.
    CleanExiHS_MFN2.
    GenevestigatoriO95140.

    Organism-specific databases

    HPAiHPA030554.

    Interactioni

    Subunit structurei

    Forms homomultimers and heteromultimers with MFN1. Oligomerization, which is mediated by the second coiled coil region, may play an essential role in mitochondrion fusion. Interacts with VAT1. Interacts with STOML2; may form heterooligomers. Interacts (phosphorylated) with PARK2. Interacts with EIF2AK3.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    LRRK2Q5S0073EBI-3324756,EBI-5323863

    Protein-protein interaction databases

    BioGridi115255. 11 interactions.
    DIPiDIP-42832N.
    IntActiO95140. 6 interactions.
    MINTiMINT-3002608.
    STRINGi9606.ENSP00000235329.

    Structurei

    3D structure databases

    ProteinModelPortaliO95140.
    SMRiO95140. Positions 695-754.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 604604CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini626 – 6261Mitochondrial intermembraneSequence Analysis
    Topological domaini648 – 757110CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei605 – 62521Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei627 – 64721Helical; Name=2Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini93 – 342250Dynamin-type GAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili391 – 43444Sequence AnalysisAdd
    BLAST
    Coiled coili695 – 73844Sequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Coiled coil, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0699.
    HOGENOMiHOG000231098.
    HOVERGENiHBG052465.
    InParanoidiO95140.
    KOiK06030.
    OMAiSTLMVTE.
    OrthoDBiEOG7HB58M.
    PhylomeDBiO95140.
    TreeFamiTF314289.

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    InterProiIPR001401. Dynamin_GTPase.
    IPR006884. Fzo/mitofusin_HR2.
    IPR027089. Mitofusin-2.
    IPR027094. Mitofusin_fam.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR10465. PTHR10465. 1 hit.
    PTHR10465:SF1. PTHR10465:SF1. 1 hit.
    PfamiPF00350. Dynamin_N. 1 hit.
    PF04799. Fzo_mitofusin. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    PROSITEiPS51718. G_DYNAMIN_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O95140-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSLLFSRCNS IVTVKKNKRH MAEVNASPLK HFVTAKKKIN GIFEQLGAYI    50
    QESATFLEDT YRNAELDPVT TEEQVLDVKG YLSKVRGISE VLARRHMKVA 100
    FFGRTSNGKS TVINAMLWDK VLPSGIGHTT NCFLRVEGTD GHEAFLLTEG 150
    SEEKRSAKTV NQLAHALHQD KQLHAGSLVS VMWPNSKCPL LKDDLVLMDS 200
    PGIDVTTELD SWIDKFCLDA DVFVLVANSE STLMQTEKHF FHKVSERLSR 250
    PNIFILNNRW DASASEPEYM EEVRRQHMER CTSFLVDELG VVDRSQAGDR 300
    IFFVSAKEVL NARIQKAQGM PEGGGALAEG FQVRMFEFQN FERRFEECIS 350
    QSAVKTKFEQ HTVRAKQIAE AVRLIMDSLH MAAREQQVYC EEMREERQDR 400
    LKFIDKQLEL LAQDYKLRIK QITEEVERQV STAMAEEIRR LSVLVDDYQM 450
    DFHPSPVVLK VYKNELHRHI EEGLGRNMSD RCSTAITNSL QTMQQDMIDG 500
    LKPLLPVSVR SQIDMLVPRQ CFSLNYDLNC DKLCADFQED IEFHFSLGWT 550
    MLVNRFLGPK NSRRALMGYN DQVQRPIPLT PANPSMPPLP QGSLTQEEFM 600
    VSMVTGLASL TSRTSMGILV VGGVVWKAVG WRLIALSFGL YGLLYVYERL 650
    TWTTKAKERA FKRQFVEHAS EKLQLVISYT GSNCSHQVQQ ELSGTFAHLC 700
    QQVDVTRENL EQEIAAMNKK IEVLDSLQSK AKLLRNKAGW LDSELNMFTH 750
    QYLQPSR 757
    Length:757
    Mass (Da):86,402
    Last modified:May 24, 2004 - v3
    Checksum:i6F859D740152DFAD
    GO
    Isoform 2 (identifier: O95140-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-302: Missing.
         303-324: FVSAKEVLNARIQKAQGMPEGG → MHPHLSTLSLPRRRSMAFLSSW
         705-757: VTRENLEQEI...FTHQYLQPSR → GETLSERSMAKSTLMLLTLLFLCSFAGAQDVLTQ

    Note: No experimental confirmation available.

    Show »
    Length:436
    Mass (Da):50,041
    Checksum:iB3DA00C339C353C8
    GO

    Sequence cautioni

    The sequence CAB70866.2 differs from that shown. Reason: Frameshift at position 581.
    The sequence BAA34389.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti521 – 5211C → P in AAD02058. (PubMed:15322553)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti69 – 691V → F in CMT2A2; in a Turkish family. 1 Publication
    Corresponds to variant rs28940296 [ dbSNP | Ensembl ].
    VAR_018607
    Natural varianti76 – 761L → P in CMT2A2; in a European family. 1 Publication
    Corresponds to variant rs28940293 [ dbSNP | Ensembl ].
    VAR_018608
    Natural varianti94 – 941R → Q in CMT2A2; in a Japanese and Russian kindred. 1 Publication
    Corresponds to variant rs28940291 [ dbSNP | Ensembl ].
    VAR_018609
    Natural varianti94 – 941R → W in CMT6. 1 Publication
    VAR_029876
    Natural varianti206 – 2061T → I in CMT6. 1 Publication
    VAR_029877
    Natural varianti233 – 2331L → V in CMT2A2. 1 Publication
    VAR_067088
    Natural varianti251 – 2511P → A in CMT2A2. 1 Publication
    Corresponds to variant rs28940295 [ dbSNP | Ensembl ].
    VAR_018610
    Natural varianti276 – 2761Q → R in CMT6. 1 Publication
    VAR_029878
    Natural varianti280 – 2801R → H in CMT2A2. 1 Publication
    Corresponds to variant rs28940294 [ dbSNP | Ensembl ].
    VAR_018611
    Natural varianti357 – 3571K → N in CMT2A2. 1 Publication
    VAR_022464
    Natural varianti361 – 3611H → Y in CMT6. 1 Publication
    VAR_029879
    Natural varianti364 – 3641R → W in CMT6 and CMT2A2. 2 Publications
    VAR_029880
    Natural varianti740 – 7401W → S in CMT2A2; in a European family. 1 Publication
    Corresponds to variant rs28940292 [ dbSNP | Ensembl ].
    VAR_018612
    Natural varianti744 – 7441E → M in CMT2A2; requires 2 nucleotide substitutions. 1 Publication
    VAR_067089

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 302302Missing in isoform 2. CuratedVSP_015159Add
    BLAST
    Alternative sequencei303 – 32422FVSAK…MPEGG → MHPHLSTLSLPRRRSMAFLS SW in isoform 2. CuratedVSP_015160Add
    BLAST
    Alternative sequencei705 – 75753VTREN…LQPSR → GETLSERSMAKSTLMLLTLL FLCSFAGAQDVLTQ in isoform 2. CuratedVSP_015161Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY028429 mRNA. Translation: AAK18728.1.
    AF036536 mRNA. Translation: AAD02058.2.
    D86987 mRNA. Translation: BAA34389.2. Different initiation.
    AK289828 mRNA. Translation: BAF82517.1.
    AL096840 Genomic DNA. Translation: CAI19087.2.
    AL096840 Genomic DNA. Translation: CAI19088.2.
    CH471130 Genomic DNA. Translation: EAW71726.1.
    BC017061 mRNA. Translation: AAH17061.1.
    AL137666 mRNA. Translation: CAB70866.2. Frameshift.
    CCDSiCCDS30587.1. [O95140-1]
    PIRiT46498.
    RefSeqiNP_001121132.1. NM_001127660.1. [O95140-1]
    NP_055689.1. NM_014874.3. [O95140-1]
    XP_005263600.1. XM_005263543.1. [O95140-1]
    XP_005263602.1. XM_005263545.1. [O95140-1]
    XP_005263604.1. XM_005263547.1. [O95140-1]
    XP_005263605.1. XM_005263548.1. [O95140-1]
    UniGeneiHs.376681.

    Genome annotation databases

    EnsembliENST00000235329; ENSP00000235329; ENSG00000116688. [O95140-1]
    ENST00000444836; ENSP00000416338; ENSG00000116688. [O95140-1]
    GeneIDi9927.
    KEGGihsa:9927.
    UCSCiuc001atn.4. human. [O95140-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Inherited peripheral neuropathies mutation db

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY028429 mRNA. Translation: AAK18728.1 .
    AF036536 mRNA. Translation: AAD02058.2 .
    D86987 mRNA. Translation: BAA34389.2 . Different initiation.
    AK289828 mRNA. Translation: BAF82517.1 .
    AL096840 Genomic DNA. Translation: CAI19087.2 .
    AL096840 Genomic DNA. Translation: CAI19088.2 .
    CH471130 Genomic DNA. Translation: EAW71726.1 .
    BC017061 mRNA. Translation: AAH17061.1 .
    AL137666 mRNA. Translation: CAB70866.2 . Frameshift.
    CCDSi CCDS30587.1. [O95140-1 ]
    PIRi T46498.
    RefSeqi NP_001121132.1. NM_001127660.1. [O95140-1 ]
    NP_055689.1. NM_014874.3. [O95140-1 ]
    XP_005263600.1. XM_005263543.1. [O95140-1 ]
    XP_005263602.1. XM_005263545.1. [O95140-1 ]
    XP_005263604.1. XM_005263547.1. [O95140-1 ]
    XP_005263605.1. XM_005263548.1. [O95140-1 ]
    UniGenei Hs.376681.

    3D structure databases

    ProteinModelPortali O95140.
    SMRi O95140. Positions 695-754.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115255. 11 interactions.
    DIPi DIP-42832N.
    IntActi O95140. 6 interactions.
    MINTi MINT-3002608.
    STRINGi 9606.ENSP00000235329.

    Protein family/group databases

    TCDBi 9.B.25.2.1. the mitochondrial inner/outer membrane fusion (mmf) family.

    PTM databases

    PhosphoSitei O95140.

    Proteomic databases

    MaxQBi O95140.
    PaxDbi O95140.
    PRIDEi O95140.

    Protocols and materials databases

    DNASUi 9927.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000235329 ; ENSP00000235329 ; ENSG00000116688 . [O95140-1 ]
    ENST00000444836 ; ENSP00000416338 ; ENSG00000116688 . [O95140-1 ]
    GeneIDi 9927.
    KEGGi hsa:9927.
    UCSCi uc001atn.4. human. [O95140-1 ]

    Organism-specific databases

    CTDi 9927.
    GeneCardsi GC01P012040.
    GeneReviewsi MFN2.
    HGNCi HGNC:16877. MFN2.
    HPAi HPA030554.
    MIMi 601152. phenotype.
    608507. gene.
    609260. phenotype.
    neXtProti NX_O95140.
    Orphaneti 99947. Autosomal dominant Charcot-Marie-Tooth disease type 2A2.
    1215. Autosomal dominant optic atrophy plus syndrome.
    64751. Hereditary motor and sensory neuropathy type 5.
    90120. Hereditary motor and sensory neuropathy type 6.
    90118. Severe early-onset axonal neuropathy due to MFN2 deficiency.
    PharmGKBi PA134986046.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0699.
    HOGENOMi HOG000231098.
    HOVERGENi HBG052465.
    InParanoidi O95140.
    KOi K06030.
    OMAi STLMVTE.
    OrthoDBi EOG7HB58M.
    PhylomeDBi O95140.
    TreeFami TF314289.

    Enzyme and pathway databases

    Reactomei REACT_24970. Factors involved in megakaryocyte development and platelet production.

    Miscellaneous databases

    ChiTaRSi MFN2. human.
    GeneWikii MFN2.
    GenomeRNAii 9927.
    NextBioi 37454.
    PROi O95140.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95140.
    Bgeei O95140.
    CleanExi HS_MFN2.
    Genevestigatori O95140.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    InterProi IPR001401. Dynamin_GTPase.
    IPR006884. Fzo/mitofusin_HR2.
    IPR027089. Mitofusin-2.
    IPR027094. Mitofusin_fam.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    PANTHERi PTHR10465. PTHR10465. 1 hit.
    PTHR10465:SF1. PTHR10465:SF1. 1 hit.
    Pfami PF00350. Dynamin_N. 1 hit.
    PF04799. Fzo_mitofusin. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 1 hit.
    PROSITEi PS51718. G_DYNAMIN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity."
      Bach D., Pich S., Soriano F.X., Vega N., Baumgartner B., Oriola J., Daugaard J.R., Lloberas J., Camps M., Zierath J.R., Rabasa-Lhoret R., Wallberg-Henriksson H., Laville M., Palacin M., Vidal H., Rivera F., Brand M., Zorzano A.
      J. Biol. Chem. 278:17190-17197(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Dysregulation of HSG triggers vascular proliferative disorders."
      Chen K.-H., Guo X., Ma D., Guo Y., Li Q., Yang D., Li P., Qiu X., Wen S., Xiao R.-P., Tang J.
      Nat. Cell Biol. 6:872-883(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DISEASE.
    3. "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
      Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
      DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Bone marrow.
    4. "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.
      , 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] (ISOFORM 1).
      Tissue: Brain.
    5. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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).
      Tissue: Pancreas.
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 553-757 (ISOFORM 1).
      Tissue: Testis.
    9. "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: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-109; 622-GLY--VAL-624 AND 657-LYS--ARG-659.
    10. "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: FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-109; SER-110 AND ARG-259.
    11. "Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis."
      Karbowski M., Lee Y.-J., Gaume B., Jeong S.-Y., Frank S., Nechushtan A., Santel A., Fuller M., Smith C.L., Youle R.J.
      J. Cell Biol. 159:931-938(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    12. "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: TISSUE SPECIFICITY.
    13. Cited for: DISEASE, VARIANTS CMT2A2 PHE-69; PRO-76; GLN-94; ALA-251; HIS-280 AND SER-740.
    14. "Identification of a novel mitochondrial complex containing mitofusin 2 and stomatin-like protein 2."
      Hajek P., Chomyn A., Attardi G.
      J. Biol. Chem. 282:5670-5681(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STOML2.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    16. "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.
    17. "PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria."
      Chen Y., Dorn G.W. II
      Science 340:471-475(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MITOPHAGY, INTERACTION WITH PARK2, PHOSPHORYLATION AT THR-111 AND SER-442 BY PINK1, UBIQUITINATION BY PARK2, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-111 AND SER-442.
    18. "Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A."
      Kijima K., Numakura C., Izumino H., Umetsu K., Nezu A., Shiiki T., Ogawa M., Ishizaki Y., Kitamura T., Shozawa Y., Hayasaka K.
      Hum. Genet. 116:23-27(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CMT2A2 ASN-357.
    19. Cited for: VARIANTS CMT6 TRP-94; ILE-206; ARG-276; TYR-361 AND TRP-364.
    20. "The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan."
      Lin K.P., Soong B.W., Yang C.C., Huang L.W., Chang M.H., Lee I.H., Antonellis A., Lee Y.C.
      PLoS ONE 6:E29393-E29393(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CMT2A2 VAL-233; TRP-364 AND MET-744.

    Entry informationi

    Entry nameiMFN2_HUMAN
    AccessioniPrimary (citable) accession number: O95140
    Secondary accession number(s): A8K1B3
    , O95572, Q5JXC3, Q5JXC4, Q9H131, Q9NSX8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2004
    Last sequence update: May 24, 2004
    Last modified: October 1, 2014
    This is version 129 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3