Biology:OTUD6B
 Generic protein structure example |
OTU domain containing 6B is a protein that in humans is encoded by the OTUD6B gene.[1]
OTUD6B is a functional deubiquitinating enzyme, a class of protease that specifically cleaves ubiquitin linkages, negating the action of ubiquitin ligases. OTUD6B, also known as DUBA5, belongs to a DUB subfamily characterized by an ovarian tumor domain (OTU).[1] OTUD6B function may be connected to growth and proliferation.[2][3] This hypothesis is supported by a recent study indicating that OTUD6B knock out mice, obtained through exon 4 deletion, are subviable and smaller in size.[4] In humans, OTUD6B mutations have been connected to an intellectual disability syndrome associated with dysmorphic features.[4]
Previous studies on model organisms (see below) cannot be verified by this editor.
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Plasma immunoglobulins | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal[5] |
| Citrobacter infection | Normal[6] |
| All tests and analysis from[7][8] |
Model organisms have been used in the study of OTUD6B function. A conditional knockout mouse line, called Otud6btm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty five tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.[7]
References
- ↑ 1.0 1.1 "Entrez Gene: OTU domain containing 6B". https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=51633. Retrieved 2011-08-30.
- ↑ "Deubiquitinase OTUD6B Isoforms are Important Regulators of Growth and Proliferation". Molecular Cancer Research 15 (2): 117–127. November 2016. doi:10.1158/1541-7786.MCR-16-0281-T. PMID 27864334.
- ↑ "Evidence for OTUD-6B participation in B lymphocytes cell cycle after cytokine stimulation". PLOS ONE 6 (1): e14514. January 2011. doi:10.1371/journal.pone.0014514. PMID 21267069.
- ↑ 4.0 4.1 Santiago-Sim, Teresa; Burrage, Lindsay C.; Ebstein, Frédéric; Tokita, Mari J.; Miller, Marcus; Bi, Weimin; Braxton, Alicia A.; Rosenfeld, Jill A. et al. (2017-04-06). "Biallelic Variants in OTUD6B Cause an Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features". American Journal of Human Genetics 100 (4): 676–688. doi:10.1016/j.ajhg.2017.03.001. ISSN 1537-6605. PMID 28343629.
- ↑ "Salmonella infection data for Otud6b". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MACN/salmonella-challenge/.
- ↑ "Citrobacter infection data for Otud6b". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MACN/citrobacter-challenge/.
- ↑ 7.0 7.1 7.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium". http://www.knockoutmouse.org/martsearch/search?query=Otud6b.
- ↑ "Mouse Genome Informatics". http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4431669.
- ↑ "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. Jun 2011. doi:10.1038/nature10163. PMID 21677750.
- ↑ "Mouse library set to be knockout". Nature 474 (7351): 262–3. Jun 2011. doi:10.1038/474262a. PMID 21677718.
- ↑ "A mouse for all reasons". Cell 128 (1): 9–13. Jan 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. 2011. doi:10.1186/gb-2011-12-6-224. PMID 21722353.
Further reading
- "Evidence for OTUD-6B participation in B lymphocytes cell cycle after cytokine stimulation". PLOS ONE 6 (1): e14514. 2011. doi:10.1371/journal.pone.0014514. PMID 21267069.
- "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Research 10 (5): 703–13. May 2000. doi:10.1101/gr.10.5.703. PMID 10810093.
- "Defining the human deubiquitinating enzyme interaction landscape". Cell 138 (2): 389–403. Jul 2009. doi:10.1016/j.cell.2009.04.042. PMID 19615732.
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