D
IPR047834

Ovarian tumor domain-containing protein 1, OTU domain

InterPro entry
Short nameOTUD1_OTU
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the OTU domain of the OTU domain-containing protein 1 (OTUD1), also known as DUBA-7 in humans.

OTUD1 is a deubiquitinating enzyme/ubiquitinyl hydrolase
3.4.19.12
, that specifically hydrolyzes 'Lys-63'-linked polyubiquitin to monoubiquitin; this specificity is facilitated by the C-terminal Ub-interacting motif (UIM) of OTUD1
[2, 3, 5, 7, 8]
. It interacts and promotes the deubiquitination of myeloid cell leukaemia 1 (MCL1), a pro-survival Bcl-2 family protein that plays important roles in cell survival, proliferation, differentiation and tumorigenesis
[6]
. OTUD1 also deubiquitinates IFN regulatory factor 3 (IRF3) and attenuates its function; IRF3 is critical for the transcription of type I IFNs in defending virus and promoting inflammatory responses
[9]
. Loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC) and Hashimoto's thyroiditis (HT)
[4]
. OTUD1 belongs to the OTU family of cysteine proteases
[1]
.

References

1.A novel superfamily of predicted cysteine proteases from eukaryotes, viruses and Chlamydia pneumoniae. Makarova KS, Aravind L, Koonin EV. Trends Biochem. Sci. 25, 50-2, (2000). View articlePMID: 10664582

2.OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. Cell 154, 169-84, (2013). View articlePMID: 23827681

3.Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Zhang Z, Fan Y, Xie F, Zhou H, Jin K, Shao L, Shi W, Fang P, Yang B, van Dam H, Ten Dijke P, Zheng X, Yan X, Jia J, Zheng M, Jin J, Ding C, Ye S, Zhou F, Zhang L. Nat Commun 8, 2116, (2017). PMID: 29235476

4.Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders. Lu D, Song J, Sun Y, Qi F, Liu L, Jin Y, McNutt MA, Yin Y. J Autoimmun 94, 156-165, (2018). PMID: 30100102

5.SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity. Yao F, Zhou Z, Kim J, Hang Q, Xiao Z, Ton BN, Chang L, Liu N, Zeng L, Wang W, Wang Y, Zhang P, Hu X, Su X, Liang H, Sun Y, Ma L. Nat Commun 9, 2269, (2018). PMID: 29891922

6.The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein. Wu L, Lin Y, Feng J, Qi Y, Wang X, Lin Q, Shi W, Zheng E, Wang W, Hou Z, Lin H, Yu C, He Y, Xu Y, Yang H, Lin L, Li L. Cancer Cell Int 19, 222, (2019). PMID: 31467488

7.Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome. Zhang L, Liu J, Qian L, Feng Q, Wang X, Yuan Y, Zuo Y, Cheng Q, Miao Y, Guo T, Zheng X, Zheng H. PLoS Pathog 14, e1007067, (2018). PMID: 29734366

8.Ovarian tumor domain-containing protein 1 deubiquitinates and stabilizes p53. Piao S, Pei HZ, Huang B, Baek SH. Cell Signal 33, 22-29, (2017). PMID: 28216291

9.OTUD1 Negatively Regulates Type I IFN Induction by Disrupting Noncanonical Ubiquitination of IRF3. Zhang Z, Wang D, Wang P, Zhao Y, You F. J Immunol 204, 1904-1918, (2020). PMID: 32075857

Cross References

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