| FBXO15 | |||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||
| Aliases | FBXO15 , FBX15, F-box protein 15 | ||||||||||||||||||||||||
| External IDs | OMIM: 609093 MGI: 1354755 HomoloGene: 17644 GeneCards: FBXO15 | ||||||||||||||||||||||||
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| Orthologs | |||||||||||||||||||||||||
| Species | Human | Mouse | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
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| RefSeq (mRNA) | |||||||||||||||||||||||||
| RefSeq (protein) | |||||||||||||||||||||||||
| Location (UCSC) | Chr 18: 74.07 – 74.15 Mb | Chr 18: 84.93 – 84.98 Mb | |||||||||||||||||||||||
| PubMed search | [3] | [4] | |||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||
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F-box protein 15 also known as Fbx15 is a protein that in humans is encoded by the FBXO15 gene. [5]
Members of the F-box protein family, such as FBXO15, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1, cullin, and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [6]
Biochemically, Fbx15 is a substrate receptor of an ubiquitin ligase belonging to the family of the F-box proteins. Differently from other F-box proteins, Fbx15 recognizes its substrate Kif1-Binding Protein (KBP) in an acetylation dependent manner. [7]
Fbxo15 is a protein expressed in undifferentiated embryonic stem cells.
It is expressed during coexpression of Oct3/4, c-Myc, Klf4, and SOX2, four genes identified to be important in embryonic stem cell self-renewal and differentiation repression. [8]
In mice having a beta-galactosidase gene knocked into the Fbx15 locus, stain was detected in ES cells, early embryos (from two-cell to blastocyst stages), and testis tissue. There is an enhancer site upstream of the Fbx15-encoding transcription gene that contains an octamer-like binding motif and a Sox-like binding motif. Reporter gene analyses demonstrated that the ES cell-specific expression required this 18-bp enhancer element located approximately 500 nucleotides upstream from the transcription initiation site. Deletion or point mutation of either motif abolished the enhancer activity. It became active in NIH 3T3 cells when Oct3/4 and Sox2 were coexpressed and cooperatively bind to the enhancer sequence.
Targeted deletion of the Fbx15 gene in mice does not result in embryonic lethality or gross developmental aberrations, despite the fact that Fbx15-/- mice are sub-fertile when compared to their wild-type counterparts. This might be explained by the fact that Fbx15-/- embryonic stem cells display a proliferation defect - caused by the accumulation of the Fbx15 substrate KBP - generating a short-term bottleneck during the early stages of embryogenesis. In fact, targeting of KBP is required to prevent an unscheduled mitochondrial biogenesis that, in naïve pluripotent stem cells, causes increased mitochondrial oxidative phosphorylation and production of reactive oxygen species. [7]
The selective expression of Fbx15 and its dependency on the activity of the pluripotency core factors Oct3/4 and Sox2 promoted the use of the expression of Fbx15 as the first marker of reprogramming of fibroblasts into induced pluripotent stem cells.
A ubiquitin ligase is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. The ubiquitin is attached to a lysine on the target protein by an isopeptide bond. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.
Skp, Cullin, F-box containing complex is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. The SCF complex also marks various other cellular proteins for destruction.
FBXL3 is a gene in humans and mice that encodes the F-box/LRR-repeat protein 3 (FBXL3). FBXL3 is a member of the F-box protein family, which constitutes one of the four subunits in the SCF ubiquitin ligase complex.
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.
F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene.
F-box only protein 7 is a protein that in humans is encoded by the FBXO7 gene. Mutations in FBXO7 have been associated with Parkinson's disease.
F-box only protein 4 is a protein that in humans is encoded by the FBXO4 gene.
F-box only protein 11 is a protein that in humans is encoded by the FBXO11 gene.
F-box/LRR-repeat protein 2 is a protein that in humans is encoded by the FBXL2 gene.
F-box only protein 2 is a protein that in humans is encoded by the FBXO2 gene.
F-box only protein 9 is a protein that in humans is encoded by the FBXO9 gene.
F-box only protein 31 is a protein that in humans is encoded by the FBXO31 gene.
F-box only protein 32 is a protein that in humans is encoded by the FBXO32 gene.
F-box only protein 28 is a protein that in humans is encoded by the FBXO28 gene.
F-box/WD repeat-containing protein 8 is a protein that in humans is encoded by the FBXW8 gene.
F-box only protein 24 is a protein that in humans is encoded by the FBXO24 gene.
F-box only protein 6 is a protein that in humans is encoded by the FBXO6 gene.
F-box and leucine-rich repeat protein 4 is a protein that in humans is encoded by the FBXL4 gene.
F-box protein 16 is a protein that in humans is encoded by the FBXO16 gene.
F-box protein 40 is a protein that in humans is encoded by the FBXO40 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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