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Details on Person UniProt:Q8IWA4 MFN1

Class:Id	ReferenceGeneProduct:150253
_chainChangeLog	chain:1-741 added on Fri February 6 2015
_displayName	UniProt:Q8IWA4 MFN1
_timestamp	2025-02-21 20:11:26
chain	chain:1-741
checksum	B7BDC22437E30A58
comment	FUNCTION Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12475957, PubMed:12759376, PubMed:27920125, PubMed:28114303). Membrane clustering requires GTPase activity (PubMed:27920125). It may involve a major rearrangement of the coiled coil domains (PubMed:27920125, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:12475957, PubMed:12759376). Overexpression induces the formation of mitochondrial networks (in vitro) (PubMed:12759376). Has low GTPase activity (PubMed:27920125, PubMed:28114303).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)SUBUNIT Homodimer, also in the absence of bound GTP (PubMed:27920125, PubMed:28114303). Forms higher oligomers in the presence of a transition state GTP analog (PubMed:28114303). Forms homomultimers and heteromultimers with MFN2 (By similarity). Oligomerization is essential for mitochondrion fusion (PubMed:27920125, PubMed:28114303). Component of a high molecular weight multiprotein complex (PubMed:12759376). Interacts with VAT1 (By similarity). Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN1.INTERACTION Detected in kidney and heart (at protein level) (PubMed:12759376). Ubiquitous (PubMed:11950885, PubMed:12759376). Expressed at slightly higher level in kidney and heart (PubMed:12759376). Isoform 2 may be overexpressed in some tumors, such as lung cancers (PubMed:11751411).DOMAIN A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.PTM Ubiquitinated by non-degradative ubiquitin by PRKN (PubMed:23933751). Deubiquitination by USP30 inhibits mitochondrial fusion (By similarity). Ubiquitinated by MARCHF5 (PubMed:20103533). 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 PRKN (PubMed:23933751).MISCELLANEOUS A truncated MFN1 construct containing the GTPase domain and the associated helix bundle is a monomer in the absence of bound GTP and a homodimer in the GTP-bound form; GDP cannot replace GTP and induce dimerization.SIMILARITY Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
description	recommendedName: Mitofusin-1 ecNumber evidence="13 14"3.6.5.- alternativeName: fullName evidence="16"Fzo homolog alternativeName: Transmembrane GTPase MFN1
geneName	MFN1
identifier	Q8IWA4
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Coiled coil Cytoplasm GTP-binding Hydrolase Membrane Mitochondrion Mitochondrion outer membrane Nucleotide-binding Proteomics identification Reference proteome Transmembrane Transmembrane helix Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	MFN1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9004806] ENSEMBL:ENSG00000171109 MFN1 [Homo sapiens]
secondaryIdentifier	MFN1_HUMAN A0A0C4DFN1 B2RAR1 D3DNR6 O15323 O60639 Q9BZB5 Q9NWQ2
sequenceLength	741
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:150254] UniProt:Q8IWA4-2 MFN1 [Homo sapiens] [ReferenceIsoform:150255] UniProt:Q8IWA4-3 MFN1 [Homo sapiens] [ReferenceIsoform:410837] UniProt:Q8IWA4-1 MFN1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:992745] MFN1 [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:5205679] K48polyUb-MFN1 [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:9834040] K63polyUb-MFN1 [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:9834985] Ub-MFN1 [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:9835005] PolyUb-MFN1 [mitochondrial outer membrane] [Homo sapiens] [EntityWithAccessionedSequence:9835008] p-S65-Ub:MFN1 [mitochondrial outer membrane] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:5205686] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position [GroupModifiedResidue:9834042] ubiquitinylated lysine (K63polyUb [cytosol]) at unknown position [GroupModifiedResidue:9834946] ubiquitinylated lysine (PolyUb [mitochondrial outer membrane]) at unknown position [GroupModifiedResidue:9834960] ubiquitinylated lysine (Ub [mitochondrial outer membrane]) at unknown position [GroupModifiedResidue:9835027] ubiquitinylated lysine (p-S65-Ub [mitochondrial outer membrane]) at unknown position
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No pathways have been reviewed or authored by UniProt:Q8IWA4 MFN1 (150253)