UniProt:Q9UKA1 FBXL5

chain
  • chain:1-691
checksum 923A1B31590E5145
comment
  • 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).COFACTOR An iron-sulfur cluster promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with ACO1/IRP1, IREB2/IRP2; the interaction depends on the [2Fe-2S] cluster. Interacts with DCTN1/p150-glued.INTERACTION The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded.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).MISCELLANEOUS Binds a diiron center, that can be bridged by a hydroxo group. The hydroxo bridge is not present when FBXL5 is in the reduced form and seems to play a critical role in regulating iron binding.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Extended N-terminus.
crossReference
databaseName UniProt
dbId 90721
description
  • recommendedName: F-box/LRR-repeat protein 5 alternativeName: F-box and leucine-rich repeat protein 5 alternativeName: F-box protein FBL4/FBL5 alternativeName: p45SKP2-like protein
displayName UniProt:Q9UKA1 FBXL5
geneName
  • FBXL5
  • FBL4
  • FBL5
  • FLR1
identifier Q9UKA1
isSequenceChanged false
keyword
  • 2Fe-2S
  • 3D-structure
  • Alternative splicing
  • Cytoplasm
  • Iron
  • Iron-sulfur
  • Leucine-rich repeat
  • Metal-binding
  • Nucleus
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Ubl conjugation
  • Ubl conjugation pathway
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • FBXL5
otherIdentifier
  • 11721315_s_at
  • 11746161_s_at
  • 16974498
  • 209004_PM_s_at
  • 209004_s_at
  • 209005_PM_at
  • 209005_at
  • 26234
  • 2761733
  • 2761735
  • 2761736
  • 2761737
  • 2761738
  • 2761739
  • 2761743
  • 2761747
  • 2761748
  • 2761749
  • 2761750
  • 2761752
  • 2761753
  • 2761755
  • 2761756
  • 2761757
  • 2761758
  • 2761759
  • 2761760
  • 2761762
  • 2761763
  • 2761766
  • 2761767
  • 2761768
  • 2761782
  • 2761783
  • 2761784
  • 2761785
  • 2761786
  • 41801_at
  • 8099449
  • A_19_P00315808
  • A_19_P00318057
  • A_19_P00318551
  • A_19_P00318998
  • A_19_P00320816
  • A_19_P00320983
  • A_19_P00321324
  • A_19_P00321572
  • A_19_P00321593
  • A_19_P00321594
  • A_19_P00322189
  • A_19_P00322431
  • A_19_P00322493
  • A_19_P00322726
  • A_19_P00322727
  • A_19_P00322955
  • A_23_P213247
  • A_32_P108748
  • GE55376
  • GO:0000151
  • GO:0003824
  • GO:0004842
  • GO:0005506
  • GO:0005515
  • GO:0005634
  • GO:0005737
  • GO:0005829
  • GO:0006879
  • GO:0016567
  • GO:0016740
  • GO:0019005
  • GO:0030163
  • GO:0031146
  • GO:0045732
  • GO:0046872
  • GO:0048471
  • GO:0051536
  • GO:0051537
  • GO:0055080
  • GO:0060586
  • GO:0098771
  • GO:0140096
  • HMNXSV003004627
  • HMNXSV003053328
  • ILMN_1673370
  • ILMN_1735051
  • ILMN_2378100
  • PH_hs_0000570
  • TC04001057.hg
  • TC04002474.hg
  • g7672733_3p_a_at
  • g7688696_3p_at
  • p25298
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • FBXL5_HUMAN
  • A8MSK4
  • B4DIB5
  • Q4W5A8
  • Q8NHP3
  • Q9NXN2
  • Q9P0I0
  • Q9P0X5
  • Q9UJT7
  • Q9UKC8
sequenceLength 691
species [Species:48887] Homo sapiens
stId uniprot:Q9UKA1
url http://purl.uniprot.org/uniprot/Q9UKA1
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