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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) Band 12q24.11 Start 109,477,402 bp End 109,536,705 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 114,518,668 bp End 114,559,230 bp
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
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 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. 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. 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.

Clinical significance

Inactivating mutations in UBE3B gene have been linked to Kaufman oculocerebrofacial syndrome (KOS), 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. 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). 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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000151148 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000029577 – 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. Braganza A, Li J, Zeng X, Yates NA, Dey NB, Andrews J, et al. (February 2017). "UBE3B Is a Calmodulin-regulated, Mitochondrion-associated E3 Ubiquitin Ligase". The Journal of Biological Chemistry. 292 (6): 2470–2484. doi:10.1074/jbc.M116.766824. PMC 5313114. PMID 28003368.
6. ^ Gong 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. PMID 12837265.
7. 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. PMID 12689446.
8. 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. PMID 31162149. S2CID 174808266.
9. 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. PMID 29160006. S2CID 24437121.
10. 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. PMID 27763745. Retrieved 2020-05-05.
11. 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. PMID 25691420. S2CID 205320002.
12. Basel-Vanagaite L, Yilmaz R, Tang S, Reuter MS, Rahner N, Grange DK, et al. (July 2014). "Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations" (PDF). Human Genetics. 133 (7): 939–949. doi:10.1007/s00439-014-1436-2. PMID 24615390. S2CID 17410752.
13. Flex E, Ciolfi A, Caputo V, Fodale V, Leoni C, Melis D, et al. (August 2013). "Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome". Journal of Medical Genetics. 50 (8): 493–499. doi:10.1136/jmedgenet-2012-101405. PMC 3717725. PMID 23687348.
14. Basel-Vanagaite L, Dallapiccola B, Ramirez-Solis R, Segref A, Thiele H, Edwards A, et al. (December 2012). "Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome". American Journal of Human Genetics. 91 (6): 998–1010. doi:10.1016/j.ajhg.2012.10.011. PMC 3516591. PMID 23200864.
15. ^ Cheon S, Kaur K, Nijem N, Tuncay IO, Kumar P, Dean M, et al. (February 2019). "The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK". Proceedings of the National Academy of Sciences of the United States of America. 116 (9): 3662–3667. Bibcode:2019PNAS..116.3662C. doi:10.1073/pnas.1818751116. PMC 6397573. PMID 30808755.
16. ^ Ambrozkiewicz 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. PMID 32249816. S2CID 214798478.

• Biology

• Genes on human chromosome 12
• Enzymes
• Human proteins