FBXL5

FBXL5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFBXL5, FBL4, FBL5, FLR1, F-box and leucine-rich repeat protein 5, F-box and leucine rich repeat protein 5
External IDsOMIM: 605655; MGI: 2152883; HomoloGene: 8129; GeneCards: FBXL5; OMA:FBXL5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001193534
NM_001193535
NM_012161

NM_001159963
NM_178729

RefSeq (protein)

NP_001180463
NP_001180464
NP_036293

NP_001153435
NP_848844

Location (UCSC)Chr 4: 15.6 – 15.68 MbChr 5: 43.9 – 43.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

F-box/LRR-repeat protein 5 is a protein that in humans is encoded by the FBXL5 gene.[5][6]

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats. Alternative splicing of this gene generates 2 transcript variants.[6]

FBXL5 is an iron and oxygen sensor. It promotes IRP2 ubiquitination and then its degradation in an iron- and oxygen-dependent manner. The cryo-EM structure of the FBXL5-IRP2 complex revealed an unexpected 2Fe2S cluster embedded in the leucine-rich repeats domain of the F-box protein in close vicinity of the protein-protein interaction interface.[7] FBXL5, therefore, is an iron-sulfur protein. FBXL5 can only engage IRP2 when its 2Fe2S cluster is in the oxidized state, which explains how oxygen tension dictates IRP2 stability.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118564Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039753Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M (October 1999). "Identification of a family of human F-box proteins". Current Biology. 9 (20): 1177–1179. Bibcode:1999CBio....9.1177C. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. S2CID 7467493.
  6. ^ a b "Entrez Gene: FBXL5 F-box and leucine-rich repeat protein 5".
  7. ^ Wang H, Shi H, Rajan M, Canarie ER, Hong S, Simoneschi D, et al. (April 2020). "FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster". Molecular Cell. 78 (1): 31–41.e5. doi:10.1016/j.molcel.2020.02.011. PMC 7159994. PMID 32126207.

Further reading

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