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FLASH GENE
Symbol FUNDC1 contributors: mct - updated : 02-10-2017
HGNC name FUN14 domain containing 1
HGNC id 28746
Location Xp11.3      Physical location : 44.382.885 - 44.402.221
Synonym symbol(s) MGC51029
DNA
TYPE functioning gene
STRUCTURE 19.34 kb     5 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1170 - 155 - 2017 28104734
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • cytoplasmic amino N-terminal domain of FUNDC1 is essential for interaction with KLC1
  • a typical MAP1LC3A-binding motif Y(18)xxL(21)
  • HOMOLOGY
    interspecies homolog to murine Fundc1 (96.1pc)
    homolog to rattus Fundc1 (96.1pc)
    Homologene
    FAMILY
    CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    basic FUNCTION
  • integral mitochondrial outer-membrane protein, is a receptor for hypoxia-induced mitophagy
  • regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy
  • regulates both mitochondrial fission or fusion and mitophagy and mediates the "coupling" across the double membrane for mitochondrial dynamics and quality control
  • is a molecular hub integrating mitochondrial fission and mitophagy at the mitochondrial-associated-membrane (MAM) in response to hypoxia
  • hypoxic preconditioning induces FUNDC1-dependent mitophagy in platelets and reduces ischemia-reperfusion (I/R)-induced heart injury
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • at mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to MAP1LC3A
  • signaling pathway linking mitochondria-damaging signals to the dephosphorylation of FUNDC1 by PGAM5, which ultimately induces mitophagy
  • BCL2L1, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy
  • different mitophagy effectors, including the mitophagy receptors BNIP3L, BNIP3 and FUNDC1 and the PINK1/Parkin pathway, have been identified to participate in the selective clearance of mitochondria
  • FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM (ER-mitochondrial contact site (MAM)) by working in concert with DNM1L and CANX under hypoxic conditions in mammalian cells
  • FUNDC1, mediate selective removal of damaged or superfluous mitochondria through their specific interaction with MAP1LC3A
  • receptor for hypoxia-induced mitophagy in mammalian cells interacting with microtubule-associated protein light chain 3 beta (MAP1LC3B) through its LC3 interaction region (LIR)
  • mitochondrial E3 ligase MARCH5, plays a role in regulating hypoxia-induced mitophagy by ubiquitylating and degrading FUNDC1
  • KLC1 may potentially compete with MAP1LC3A, a key component for autophagosome formation, to interact with FUNDC1
  • FUNDC1 is a substrate of MARCH5, a mitochondrially localized E3 ubiquitin ligase
  • melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARG/FUNDC1/mitophagy pathways
  • cell & other
    REGULATION
    Other phosphorylation of Tyr18 of FUNDC1 serves as a molecular switch for mitophagy
    hypoxia induced dephosphorylation of FUNDC1 and enhanced its interaction with MAP1LC3A for selective mitophagy
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS