FBXL5

FBXL5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3U9J, 3U9M, 3V5X, 3V5Y, 3V5Z
Identifiers
Aliases	FBXL5, FBL4, FBL5, FLR1, F-box and leucine-rich repeat protein 5, F-box and leucine rich repeat protein 5
External IDs	OMIM: 605655; MGI: 2152883; HomoloGene: 8129; GeneCards: FBXL5; OMA:FBXL5 - orthologs
Gene location (Human)
Chr.	Chromosome 4 (human)
End	15,681,679 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	43,978,980 bp
RNA expression pattern
	Top expressed in
	monocyte; ; Epithelium of choroid plexus; ; Achilles tendon; ; kidney tubule; ; blood; ; seminal vesicula; ; germinal epithelium; ; oocyte; ; secondary oocyte; ; sperm;
	Top expressed in
	spermatocyte; ; granulocyte; ; otolith organ; ; utricle; ; spermatid; ; neural layer of retina; ; lobe of cerebellum; ; gastrula; ; cerebellar vermis; ; habenula;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	iron ion binding; protein binding; metal ion binding; ubiquitin-protein transferase activity;
Cellular component	ubiquitin ligase complex; cytoplasm; SCF ubiquitin ligase complex; perinuclear region of cytoplasm; cytosol;
Biological process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; iron ion homeostasis; protein polyubiquitination; cellular iron ion homeostasis; post-translational protein modification; ubiquitin-dependent protein catabolic process;
	Sources:Amigo / QuickGO
Orthologs
	26234
	242960
	ENSG00000118564
	ENSMUSG00000039753
	Q9UKA1
	Q8C2S5
	NM_001193534; NM_001193535; NM_012161
	NM_001159963; NM_178729
	NP_001180463; NP_001180464; NP_036293
	NP_001153435; NP_848844
	Wikidata
View/Edit Human	View/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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000118564 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039753 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: FBXL5 F-box and leucine-rich repeat protein 5".
^ 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.

Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (October 1999). "A family of mammalian F-box proteins". Current Biology. 9 (20): 1180–1182. Bibcode:1999CBio....9.1180W. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037. S2CID 14341845.
Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (July 2000). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–47. doi:10.1006/geno.2000.6211. PMID 10945468.
Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–D418. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
Zhang N, Liu J, Ding X, Aikhionbare F, Jin C, Yao X (July 2007). "FBXL5 interacts with p150Glued and regulates its ubiquitination". Biochemical and Biophysical Research Communications. 359 (1): 34–39. doi:10.1016/j.bbrc.2007.05.068. PMID 17532294.

This article on a gene on human chromosome 4 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000118564 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000039753 – Ensembl, 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.

[pmid10531035-5] 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.

[entrez-6] "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.

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FBXL5

References

Further reading