FBXL5
entrez
26234
canonical
uniprot
Q9UKA1
canonical
ensembl
ENSG00000118564
resolver
ensp
ENSP00000344866
resolver
ensp
ENSP00000408679
resolver
ensp
ENSP00000554072
resolver
ensp
ENSP00000554074
resolver
genesymbol
FBXL5
resolver
genesymbol_syn
FBL4
resolver
genesymbol_syn
FBL5
resolver
genesymbol_syn
FLR1
resolver
hgnc
HGNC:13602
resolver
uniprot
A8MSK4
resolver
uniprot
B4DIB5
resolver
uniprot
Q4W5A8
resolver
uniprot
Q8NHP3
resolver
uniprot
Q9NXN2
resolver
uniprot
Q9P0I0
resolver
uniprot
Q9P0X5
resolver
uniprot
Q9UJT7
resolver
uniprot
Q9UKC8
resolver
uniprot_entry
FBXL5_HUMAN
resolver
uniprot_sec
A8MSK4
resolver
uniprot_sec
B4DIB5
resolver
uniprot_sec
Q4W5A8
resolver
uniprot_sec
Q8NHP3
resolver
uniprot_sec
Q9NXN2
resolver
uniprot_sec
Q9P0I0
resolver
uniprot_sec
Q9P0X5
resolver
uniprot_sec
Q9UJT7
resolver
uniprot_sec
Q9UKC8
resolver
activity_regulation
ACTIVITY REGULATION: An iron-sulfur cluster promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations. {ECO:0000269|PubMed:32126207}.
uniprot
proteins
amino_acid_sequence
MAPFPEEVDVFTAPHWRMKQLVGLYCDKLSKTNFSNNNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRSQTIYNVHSDNKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCSQKDTAELLRGLSLWNHAEERQKFFKYSVDEKSDKEAEVSEHSTGITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLYPVHWARGDWYSGPATELDTEPDDEWVKNRKDESRAFHEWDEDADIDESEESAEESIAISIAQMEKRLLHGLIHNVLPYVGTSVKTLVLAYSSAVSSKMVRQILELCPNLEHLDLTQTDISDSAFDSWSWLGCCQSLRHLDLSGCEKITDVALEKISRALGILTSHQSGFLKTSTSKITSTAWKNKDITMQSTKQYACLHDLTNKGIGEEIDNEHPWTKPVSSENFTSPYVWMLDAEDLADIEDTVEWRHRNVESLCVMETASNFSCSTSGCFSKDIVGLRTSVCWQQHCASPAFAYCGHSFCCTGTALRTMSSLPESSAMCRKAARTRLPRGKDLIYFGSEKSDQETGRVLLFLSLSGCYQITDHGLRVLTLGGGLPYLEHLNLSGCLTITGAGLQDLVSACPSLNDEYFYYCDNINGPHADTASGCQNLQCGFRACCRSGE
uniprot
proteins
function
FUNCTION: Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2 (PubMed:19762596, PubMed:19762597). The C-terminal domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon oxidation, promotes binding to IRP2 to effect its oxygen-dependent degradation (PubMed:32126207). Under iron deficiency conditions, the N-terminal hemerythrin-like (Hr) region, which contains a diiron metal center, cannot bind iron and undergoes conformational changes that destabilize the FBXL5 protein and cause its ubiquitination and degradation (PubMed:19762596, PubMed:19762597). When intracellular iron levels start rising, the Hr region is stabilized (PubMed:19762596, PubMed:19762597). Additional increases in iron levels facilitate the assembly and incorporation of a redox active [2Fe-2S] cluster in the C-terminal domain (PubMed:32126207). Only when oxygen level is high enough to maintain the cluster in its oxidized state can FBXL5 recruit IRP2 as a substrate for polyubiquitination and degradation (PubMed:32126207). Promotes ubiquitination and subsequent degradation of the dynactin complex component DCTN1 (PubMed:17532294). Within the nucleus, promotes the ubiquitination of SNAI1; preventing its interaction with DNA and promoting its degradation (PubMed:24157836). Negatively regulates DNA damage response by mediating the ubiquitin-proteasome degradation of the DNA repair protein NABP2 (PubMed:25249620). {ECO:0000269|PubMed:17532294, ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597, ECO:0000269|PubMed:32126207}.
uniprot
proteins
mass_dalton
78555
uniprot
proteins
mutagenesis
MUTAGEN 15; /note="H->A: Abolishes iron-binding and promotes its degradation."; /evidence="ECO:0000269|PubMed:19762596"; MUTAGEN 57; /note="H->A: Abolishes iron-binding and promotes its degradation."; /evidence="ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597"; MUTAGEN 61; /note="E->A: Abolishes iron-binding and promotes its degradation."; /evidence="ECO:0000269|PubMed:19762597"; MUTAGEN 662; /note="C->S: More than 90% loss of binding to IREB2/IRP2."; /evidence="ECO:0000269|PubMed:32126207"; MUTAGEN 676; /note="C->S: More than 90% loss of binding to IREB2/IRP2."; /evidence="ECO:0000269|PubMed:32126207"; MUTAGEN 686; /note="C->S: More than 90% loss of binding to IREB2/IRP2."; /evidence="ECO:0000269|PubMed:32126207"; MUTAGEN 687; /note="C->S: More than 90% loss of binding to IREB2/IRP2."; /evidence="ECO:0000269|PubMed:32126207
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Polybiquitinated upon iron and oxygen depletion, leading to its degradation by the proteasome. Ubiquitination is regulated by the hemerythrin-like region that acts as an oxygen and iron sensor. Undergoes constitutive ubiquitin-dependent degradation at the steady state by HERC2 (PubMed:24778179). {ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597, ECO:0000269|PubMed:24778179}.
uniprot
proteins
pubmed
10531035
uniprot
proteins
pubmed
10531037
uniprot
proteins
pubmed
10945468
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17532294
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19762596
uniprot
proteins
pubmed
19762597
uniprot
proteins
pubmed
22253436
uniprot
proteins
pubmed
22492618
uniprot
proteins
pubmed
24157836
uniprot
proteins
pubmed
24778179
uniprot
proteins
pubmed
25249620
uniprot
proteins
pubmed
32126207
uniprot
proteins
sequence_length
691
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000269|PubMed:17532294}. Nucleus {ECO:0000269|PubMed:24157836}.
uniprot
proteins