Ubiquitin-Protein Ligase E3B (UBE3B) is an enzyme encoded by UBE3B gene in humans. UBE3B has an N-terminal IQ motif, which mediates calcium-independent calmodulin binding[5] and a large C-terminal catalytic HECT domain.
UBE3B gene was discovered in 1996 by the group of Margaret Lomax at the University of Michigan Medical School.[6] Differential mRNA expression study, to reveal genes upregulated after acoustic trauma in the chick basilar papilla, led to identification of cDNA which exhibited 84% of identity of uncharacterized human cDNA.[7] Interestingly, its expression dramatically increased in the regions of damaged chick inner ear upon noise-induced trauma. In 2003, human and mouse UBE3B gene was cloned and characterized by its discoverers.[6]
Deletion of murine ortholog Ube3b leads to severe developmental delay in mice.[15][16] The conventional knockout of Ube3b leads to a growth retardation, decreased grip strength, and loss of vocalization associated with the metabolic disease with nucleotide metabolism and the tricarboxylic acid cycle being the most affected. Such metabolic disturbances were also found in KOS patients. In this context, UBE3B ubiquitinated α-ketoacid dehydrogenase kinase (BCKDK).[15]Forebrain-specific conditional Ube3b knockout mice showed impaired spatial learning, altered social interactions, and repetitive behaviors. Ube3b knockout neurons exhibited decreased dendritic branching, increased density and aberrant morphology of dendritic spines, altered synaptic physiology, and changes in hippocampal circuit activity. Dendritic and spine phenotype was regulated by Ube3b in a cell-autonomous manner. Murine Ube3b ubiquitinated the catalytic γ-subunit of calcineurin, Ppp3cc, the overexpression of which phenocopied Ube3b loss with regard to dendrite branching and dendritic spine density.[16]
^ abGong TW, Huang L, Warner SJ, Lomax MI (August 2003). "Characterization of the human UBE3B gene: structure, expression, evolution, and alternative splicing". Genomics. 82 (2): 143–152. doi:10.1016/s0888-7543(03)00111-3. PMID12837265.
^Lomax MI, Gong TW, Cho Y, Huang L, Oh SH, Adler HJ, et al. (2001). "Differential Gene Expression Following Noise Trauma in Birds and Mammals". Noise & Health. 3 (11): 19–35. PMID12689446.
^Galarreta CI, Wigby KM, Jones MC (October 2019). "Further phenotypic characterization of Kaufman oculocerebrofacial syndrome: report of five new cases and literature review". Clinical Dysmorphology. 28 (4): 175–183. doi:10.1097/MCD.0000000000000282. PMID31162149. S2CID174808266.
^Yilmaz R, Szakszon K, Altmann A, Altunoglu U, Senturk L, McGuire M, et al. (January 2018). "Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients". American Journal of Medical Genetics. Part A. 176 (1): 187–193. doi:10.1002/ajmg.a.38538. PMID29160006. S2CID24437121.
^Brabbing-Goldstein D, Basel-Salmon L (1993). "Kaufman Oculocerebrofacial Syndrome". In Adam MP, Ardinger HH, Pagon RA, Wallace SE (eds.). GeneReviews®. University of Washington, Seattle. PMID27763745. Retrieved 2020-05-05.
^Pedurupillay CR, Barøy T, Holmgren A, Blomhoff A, Vigeland MD, Sheng Y, et al. (March 2015). "Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B". American Journal of Medical Genetics. Part A. 167A (3): 657–663. doi:10.1002/ajmg.a.36944. PMID25691420. S2CID205320002.
^ abAmbrozkiewicz MC, Borisova E, Schwark M, Ripamonti S, Schaub T, Smorodchenko A, et al. (June 2021). "The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc". Molecular Psychiatry. 26 (6): 1980–1995. doi:10.1038/s41380-020-0714-8. PMID32249816. S2CID214798478.
