OTUD6B

OTU domain containing 6B is a protein that in humans is encoded by the OTUD6B gene.[5]

OTUD6B
Identifiers
Aliases	OTUD6B, DUBA-5, DUBA5, CGI-77, OTU domain containing 6B, IDDFSDA, OTU deubiquitinase 6B
External IDs	OMIM: 612021 MGI: 1919451 HomoloGene: 6064 GeneCards: OTUD6B
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q21.3 Start 91,070,196 bp[1] End 91,087,095 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 A1 Start 14,809,498 bp[2] End 14,826,587 bp[2]
Gene ontology Molecular function • peptidase activity • cysteine-type peptidase activity • hydrolase activity • thiol-dependent ubiquitinyl hydrolase activity • thiol-dependent ubiquitin-specific protease activity Cellular component • eukaryotic translation initiation factor 4F complex Biological process • proteolysis • cellular proliferation • protein deubiquitination • negative regulation of translation • proteasome assembly • positive regulation of translation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	51633	72201
Ensembl	ENSG00000155100	ENSMUSG00000040550
UniProt	Q8N6M0	Q8K2H2
RefSeq (mRNA)	NM_001286745 NM_016023	NM_152812
RefSeq (protein)	NP_001273674 NP_057107	NP_690025
Location (UCSC)	Chr 8: 91.07 – 91.09 Mb	Chr 4: 14.81 – 14.83 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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).[5] OTUD6B function may be connected to growth and proliferation.[6][7] 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.[8] In humans, OTUD6B mutations have been connected to an intellectual disability syndrome associated with dysmorphic features.[8]

Previous studies on model organisms (see below) cannot be verified by this editor.

Otud6b knockout mouse phenotype

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[9]
Citrobacter infection	Normal[10]
All tests and analysis from[11][12]

Model organisms have been used in the study of OTUD6B function. A conditional knockout mouse line, called Otud6b^{tm1a(EUCOMM)Wtsi}[13][14] 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.[15][16][17]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[11][18] Twenty five tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000155100 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040550 - 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. "Entrez Gene: OTU domain containing 6B". Retrieved 2011-08-30.
6. Sobol A, Askonas C, Alani S, Weber MJ, Ananthanarayanan V, Osipo C, Bocchetta M (November 2016). "Deubiquitinase OTUD6B Isoforms are Important Regulators of Growth and Proliferation". Molecular Cancer Research. 15: 117–127. doi:10.1158/1541-7786.MCR-16-0281-T. PMC 5290186. PMID 27864334.
7. Xu Z, Zheng Y, Zhu Y, Kong X, Hu L (January 2011). "Evidence for OTUD-6B participation in B lymphocytes cell cycle after cytokine stimulation". PLOS ONE. 6 (1): e14514. doi:10.1371/journal.pone.0014514. PMC 3022568. PMID 21267069.
8. Santiago-Sim, Teresa; Burrage, Lindsay C.; Ebstein, Frédéric; Tokita, Mari J.; Miller, Marcus; Bi, Weimin; Braxton, Alicia A.; Rosenfeld, Jill A.; Shahrour, Maher (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. PMC 5384096. PMID 28343629.
9. "Salmonella infection data for Otud6b". Wellcome Trust Sanger Institute.
10. "Citrobacter infection data for Otud6b". Wellcome Trust Sanger Institute.
11. 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.
12. Mouse Resources Portal, Wellcome Trust Sanger Institute.
13. "International Knockout Mouse Consortium". Archived from the original on 2012-03-20. Retrieved 2012-01-05.
14. "Mouse Genome Informatics".
15. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
16. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
17. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
18. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Xu Z, Zheng Y, Zhu Y, Kong X, Hu L (2011). "Evidence for OTUD-6B participation in B lymphocytes cell cycle after cytokine stimulation". PLOS ONE. 6 (1): e14514. doi:10.1371/journal.pone.0014514. PMC 3022568. PMID 21267069.
• Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W (May 2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Research. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093.
• Sowa ME, Bennett EJ, Gygi SP, Harper JW (Jul 2009). "Defining the human deubiquitinating enzyme interaction landscape". Cell. 138 (2): 389–403. doi:10.1016/j.cell.2009.04.042. PMC 2716422. PMID 19615732.