UBE3B
Identifiers
Aliases	UBE3B, BPIDS, KOS, ubiquitin protein ligase E3B
External IDs	OMIM: 608047; MGI: 1891295; HomoloGene: 13775; GeneCards: UBE3B; OMA: UBE3B - orthologs
Gene location ( Human) Chr. Chromosome 12 (human) [1] Band 12q24.11 Start 109,477,402 bp [1] End 109,536,705 bp [1]
Gene location ( Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 F Start 114,518,668 bp [2] End 114,559,230 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte frontal pole endothelial cell Brodmann area 10 paraflocculus of cerebellum muscle of thigh stromal cell of endometrium gastrocnemius muscle left ventricle Top expressed in muscle of thigh triceps brachii muscle ankle skeletal muscle tissue vastus lateralis muscle interventricular septum temporal muscle sternocleidomastoid muscle digastric muscle medial head of gastrocnemius muscle More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity ubiquitin-protein transferase activity ubiquitin protein ligase activity ubiquitin conjugating enzyme activity Cellular component cytoplasm Biological process protein ubiquitination protein polyubiquitination ubiquitin-dependent protein catabolic process Sources: Amigo / QuickGO
Orthologs Species Human Mouse Entrez 89910 117146 Ensembl ENSG00000151148 ENSMUSG00000029577 UniProt Q7Z3V4 Q9ES34 RefSeq (mRNA) NM_001270449 NM_001270450 NM_001270451 NM_130466 NM_183414 NM_183415 NM_054093 NM_001331219 RefSeq (protein) NP_001257378 NP_001257379 NP_001257380 NP_569733 NP_904324 NP_001318148 NP_473434 Location (UCSC) Chr 12: 109.48 – 109.54 Mb Chr 5: 114.52 – 114.56 Mb PubMed search [3] [4]
Wikidata
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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.

Discovery

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]

Clinical significance

Inactivating mutations in UBE3B gene have been linked to Kaufman oculocerebrofacial syndrome (KOS), ^{[8] [9] [10] [11] [12] [13] [14]} a severe developmental disorder. Most mutations are loss-of-function and lead to premature stop codon. However, some mutations are of single amino acid substitution type and these occur in the low complexity region, or in the catalytic HECT domain.

Mouse models

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]

References