Mouse anti-Human/Mouse/Rat sapiens (Human) FBXO22 Monoclonal Antibody

Function

Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that is implicated in the control of various cellular processes such as cell cycle control, transcriptional regulation, DNA damage repair, and apoptosis. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function. Acts as a key regulator of histone methylation marks namely H3K9 and H3K36 methylation through the regulation of histone demethylase KDM4A protein levels (PubMed:21768309). In complex with KDM4A, also regulates the abundance of TP53 by targeting methylated TP53 for degradation at the late senescent stage (PubMed:26868148). Under oxidative stress, promotes the ubiquitination and degradation of BACH1. Mechanistically, reactive oxygen species (ROS) covalently modify cysteine residues on the bZIP domain of BACH1, leading to its release from chromatin and making it accessible to FBXO22 (PubMed:39504958). Upon amino acid depletion, mediates 'Lys-27'-linked ubiquitination of MTOR and thereby inhibits substrate recruitment to mTORC1 (PubMed:37979583). Also inhibits SARS-CoV-2 replication by inducing NSP5 degradation (PubMed:39223933)

Subcellular Location

Cytoplasm; Nucleus; Cytoplasm, myofibril, sarcomere, Z line

Disease Association

Tayoun-Maawali syndrome (TYMAS) : An autosomal recessive pleiotropic syndrome characterized by multiple abnormalities encompassing early growth restriction, neurodevelopmental delay, and craniofacial, cardiovascular, gastrointestinal, urinary and endocrine anomalies. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Predominantly expressed in liver, also enriched in cardiac muscle

Subunit

(Microbial infection) Interacts with SARS_COV-2 protein NSP5; this interaction attenuates NSP5-mediated inhibition of innate immunity

• Tan P. et al. FBX22p44: a novel human F-box protein predominantly expressed in the liver. (JUL-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Zody M.C. et al. Analysis of the DNA sequence and duplication history of human chromosome 15. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Cenciarelli C. et al. Identification of a family of human F-box proteins. — Curr. Biol. (1999)
• Gauci S. et al. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. — Anal. Chem. (2009)
• Choudhary C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. — Science (2009)
• Burkard T.R. et al. Initial characterization of the human central proteome. — BMC Syst. Biol. (2011)