FUNDC1
entrez
139341
canonical
uniprot
Q8IVP5
canonical
ensembl
ENSG00000069509
resolver
ensp
ENSP00000367284
resolver
enst
ENST00000378045
resolver
genesymbol
FUNDC1
resolver
hgnc
HGNC:28746
resolver
uniprot_entry
FUND1_HUMAN
resolver
amino_acid_sequence
MATRNPPPQDYESDDDSYEVLDLTEYARRHQWWNRVFGHSSGPMVEKYSVATQIVMGGVTGWCAGFLFQKVGKLAATAVGGGFLLLQIASHSGYVQIDWKRVEKDVNKAKRQIKKRANKAAPEINNLIEEATEFIKQNIVISSGFVGGFLLGLAS
uniprot
proteins
function
FUNCTION: Integral mitochondrial outer-membrane protein that mediates the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) (PubMed:33972548). In turn, mediates angiogenesis and neoangiogenesis through interference with intracellular Ca(2+) communication and regulation of the vascular endothelial growth factor receptor KDR/VEGFR2 expression at both mRNA and protein levels (PubMed:33972548). Also acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality and homeostasis, by interacting with and recruiting LC3 protein family to mitochondria (PubMed:22267086, PubMed:24671035, PubMed:24746696, PubMed:27653272). Mechanistically, recruits DRP1 at ER-mitochondria contact sites leading to DRP1 oligomerization and GTPase activity to facilitate mitochondrial fission during hypoxia (PubMed:27145933, PubMed:33978709). Additionally, plays a role in hepatic ferroptosis by interacting directly with glutathione peroxidase/GPX4 to facilitate its recruitment into mitochondria through TOM/TIM complex where it is degraded by mitophagy (PubMed:36828120). {ECO:0000269|PubMed:22267086, ECO:0000269|PubMed:24671035, ECO:0000269|PubMed:24746696, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27653272, ECO:0000269|PubMed:33972548, ECO:0000269|PubMed:33978709, ECO:0000269|PubMed:36828120}.
uniprot
proteins
mass_dalton
17178
uniprot
proteins
mutagenesis
MUTAGEN 17; /note="S->A: Almost complete loss of interaction with MAP1 LC3 family proteins."; /evidence="ECO:0000269|PubMed:24671035"; MUTAGEN 18; /note="Y->A: Impairs interaction with MAP1 LC3 family proteins."; /evidence="ECO:0000269|PubMed:22267086"; MUTAGEN 18; /note="Y->W: Abolishes phosphorylation by SRC."; /evidence="ECO:0000269|PubMed:22267086"; MUTAGEN 20; /note="V->A: Significantly impaired mitophagy-inducing ability."; /evidence="ECO:0000269|PubMed:27653272"; MUTAGEN 21; /note="L->A: Impairs interaction with MAP1 LC3 family proteins."; /evidence="ECO:0000269|PubMed:22267086"; MUTAGEN 32..33; /note="WW->AA: Does not affect interaction with MAP1 LC3 family proteins."; MUTAGEN 118; /note="N->A: Loss of binding to ULK1 and inhibition of mitophagy."; /evidence="ECO:0000269|PubMed:24671035"; MUTAGEN 119; /note="K->R: Strong loss of ubiquitination level."; /evidence="ECO:0000269|PubMed:33978709
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-13 by CK2 and at Tyr-18 by SRC inhibits activation of mitophagy. Following hypoxia, dephosphorylated at Tyr-18, leading to interaction with MAP1 LC3 family proteins and triggering mitophagy. Dephosphorylation is mediated by PGAM5 (PubMed:24746696). Phosphorylated by ULK1 at Ser-17 which enhances FUNDC1 binding to LC3 (PubMed:24671035). {ECO:0000269|PubMed:22267086, ECO:0000269|PubMed:24671035, ECO:0000269|PubMed:24746696, ECO:0000269|PubMed:27653272}.; PTM: Ubiquitinated on Lys-119. Deubiquitinated by USP19; leading to hypoxia-induced DRP1 oligomerization and GTPase activity. {ECO:0000269|PubMed:33978709}.
uniprot
proteins
protein_family
FUN14 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
22267086
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24671035
uniprot
proteins
pubmed
24700572
uniprot
proteins
pubmed
24746696
uniprot
proteins
pubmed
27145933
uniprot
proteins
pubmed
27653272
uniprot
proteins
pubmed
27757847
uniprot
proteins
pubmed
33972548
uniprot
proteins
pubmed
33978709
uniprot
proteins
pubmed
36828120
uniprot
proteins
sequence_length
155
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000269|PubMed:22267086, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:33978709}; Multi-pass membrane protein {ECO:0000269|PubMed:22267086}.
uniprot
proteins
transmembrane_region
TRANSMEM 48..68; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 75..95; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 134..154; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins