FBXO5

F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene.[5][6][7]

FBXO5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2M6N, 4UI9
Identifiers
Aliases	FBXO5, EMI1, FBX5, Fbxo31, F-box protein 5
External IDs	OMIM: 606013 MGI: 1914391 HomoloGene: 8135 GeneCards: FBXO5
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q25.2 Start 152,970,519 bp[1] End 152,983,579 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 A1 Start 5,799,160 bp[2] End 5,805,600 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • metal ion binding • GO:0001948 protein binding • protein kinase binding • GO:0090645, GO:0061637 ubiquitin ligase inhibitor activity • anaphase-promoting complex binding Cellular component • cytoplasm • cytosol • spindle • nucleoplasm • cytoskeleton • cell nucleus • meiotic spindle Biological process • vesicle organization • regulation of meiotic nuclear division • microtubule polymerization • negative regulation of meiotic nuclear division • regulation of transcription involved in G1/S transition of mitotic cell cycle • cell division • spindle assembly • oocyte maturation • regulation of mitotic cell cycle • cell cycle • spindle assembly involved in female meiosis I • regulation of mitotic nuclear division • GO:0060564, GO:1904190 negative regulation of ubiquitin protein ligase activity • anaphase-promoting complex-dependent catabolic process • negative regulation of mitotic metaphase/anaphase transition • regulation of DNA replication • positive regulation of cell proliferation • positive regulation of G2/M transition of mitotic cell cycle • negative regulation of DNA endoreduplication • positive regulation of osteoblast differentiation • negative regulation of ubiquitin-protein transferase activity • positive regulation of biomineral tissue development • positive regulation of mesenchymal stem cell migration • negative regulation of cellular senescence • negative regulation of response to DNA damage stimulus • protein ubiquitination • regulation of mitotic cell cycle phase transition Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	26271	67141
Ensembl	ENSG00000112029	ENSMUSG00000019773
UniProt	Q9UKT4	Q7TSG3
RefSeq (mRNA)	NM_001142522 NM_012177	NM_025995
RefSeq (protein)	NP_001135994 NP_036309	NP_080271
Location (UCSC)	Chr 6: 152.97 – 152.98 Mb	Chr 10: 5.8 – 5.81 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

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 the 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 Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.[7] Moreover, Emi1 also assembles a CRL1 complex that targets RAD51 for ubiquitin-mediated degradation.[8]

Disease

Gene and protein expression of FBXO5/Emi1 are increased in many human cancers and increased expression has been shown to cause chromosome instability and cancer.[9]

Interactions

FBXO5 has been shown to interact with:

• CDC20,[10]
• FZR1,[10]
• SKP1A.[11] and
• RAD51.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000112029 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019773 - 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.
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): 1177–9. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. S2CID 7467493.
6. Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (October 1999). "A family of mammalian F-box proteins". Current Biology. 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037. S2CID 14341845.
7. "Entrez Gene: FBXO5 F-box protein 5".
8. Marzio A, Puccini J, Kwon Y, Maverakis NK, Arbini A, Sung P, et al. (January 2019). "The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers". Molecular Cell. 73 (2): 224–237.e6. doi:10.1016/j.molcel.2018.11.003. PMC 6995265. PMID 30554948.
9. Vaidyanathan S, Cato K, Tang L, Pavey S, Haass NK, Gabrielli BG, Duijf PH (October 2016). "In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis". Oncogene. 35 (41): 5446–5455. doi:10.1038/onc.2016.94. PMID 27065322. S2CID 13540659.
10. Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK (May 2002). "E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)". Nature Cell Biology. 4 (5): 358–66. doi:10.1038/ncb785. PMID 11988738. S2CID 25403043.
11. 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): 1177–9. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. S2CID 7467493.

Further reading

• Gubin AN, Njoroge JM, Bouffard GG, Miller JL (July 1999). "Gene expression in proliferating human erythroid cells". Genomics. 59 (2): 168–77. doi:10.1006/geno.1999.5855. PMID 10409428.
• Chiaur DS, Murthy S, Cenciarelli C, Parks W, Loda M, Inghirami G, et al. (2000). "Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors". Cytogenetics and Cell Genetics. 88 (3–4): 255–8. doi:10.1159/000015532. PMID 10828603. S2CID 431704.
• Reimann JD, Freed E, Hsu JY, Kramer ER, Peters JM, Jackson PK (June 2001). "Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex". Cell. 105 (5): 645–55. doi:10.1016/S0092-8674(01)00361-0. PMID 11389834. S2CID 16366514.
• Reimann JD, Jackson PK (April 2002). "Emi1 is required for cytostatic factor arrest in vertebrate eggs". Nature. 416 (6883): 850–4. Bibcode:2002Natur.416..850R. doi:10.1038/416850a. PMID 11976684. S2CID 4403891.
• Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK (May 2002). "E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)". Nature Cell Biology. 4 (5): 358–66. doi:10.1038/ncb785. PMID 11988738. S2CID 25403043.
• Li Z, Hu CY, Mo BQ, Xu JD, Zhao Y (April 2003). "[Effect of beta-carotene on gene expression of breast cancer cells]". AI Zheng = Aizheng = Chinese Journal of Cancer. 22 (4): 380–4. PMID 12703993.
• Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD, Jackson PK (June 2003). "Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase". Developmental Cell. 4 (6): 813–26. doi:10.1016/S1534-5807(03)00153-9. PMID 12791267.
• Moshe Y, Boulaire J, Pagano M, Hershko A (May 2004). "Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome". Proceedings of the National Academy of Sciences of the United States of America. 101 (21): 7937–42. Bibcode:2004PNAS..101.7937M. doi:10.1073/pnas.0402442101. PMC 419535. PMID 15148369.
• Hansen DV, Loktev AV, Ban KH, Jackson PK (December 2004). "Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1". Molecular Biology of the Cell. 15 (12): 5623–34. doi:10.1091/mbc.E04-07-0598. PMC 532041. PMID 15469984.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Eldridge AG, Loktev AV, Hansen DV, Verschuren EW, Reimann JD, Jackson PK (January 2006). "The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1". Cell. 124 (2): 367–80. doi:10.1016/j.cell.2005.10.038. PMID 16439210.
• Lehman NL, Verschuren EW, Hsu JY, Cherry AM, Jackson PK (July 2006). "Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells". Cell Cycle. 5 (14): 1569–73. doi:10.4161/cc.5.14.2925. PMID 16861914.
• Miller JJ, Summers MK, Hansen DV, Nachury MV, Lehman NL, Loktev A, Jackson PK (September 2006). "Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor". Genes & Development. 20 (17): 2410–20. doi:10.1101/gad.1454006. PMC 1560415. PMID 16921029.
• Marangos P, Verschuren EW, Chen R, Jackson PK, Carroll J (January 2007). "Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1)". The Journal of Cell Biology. 176 (1): 65–75. doi:10.1083/jcb.200607070. PMC 2063628. PMID 17190794.