Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJBLG5R)

• DOT Name: E3 ubiquitin-protein ligase TRIM22 (TRIM22)
• Synonyms: EC 2.3.2.27; 50 kDa-stimulated trans-acting factor; RING finger protein 94; RING-type E3 ubiquitin transferase TRIM22; Staf-50; Tripartite motif-containing protein 22
• Gene Name: TRIM22
• Related Disease:
  Autoimmune disease
  Crohn disease
  Endometrial cancer
  Endometrial carcinoma
  Hepatitis B virus infection
  Influenza
  Non-small-cell lung cancer
  Sjogren syndrome
  Systemic lupus erythematosus
  Tuberculosis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  HIV infectious disease
  Neoplasm
  Hepatitis C virus infection
  Inflammatory bowel disease
• UniProt ID: TRI22_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF00622 ; PF00643 ; PF13445
• Sequence:
  MDFSVKVDIEKEVTCPICLELLTEPLSLDCGHSFCQACITAKIKESVIISRGESSCPVCQ
  TRFQPGNLRPNRHLANIVERVKEVKMSPQEGQKRDVCEHHGKKLQIFCKEDGKVICWVCE
  LSQEHQGHQTFRINEVVKECQEKLQVALQRLIKEDQEAEKLEDDIRQERTAWKNYIQIER
  QKILKGFNEMRVILDNEEQRELQKLEEGEVNVLDNLAAATDQLVQQRQDASTLISDLQRR
  LRGSSVEMLQDVIDVMKRSESWTLKKPKSVSKKLKSVFRVPDLSGMLQVLKELTDVQYYW
  VDVMLNPGSATSNVAISVDQRQVKTVRTCTFKNSNPCDFSAFGVFGCQYFSSGKYYWEVD
  VSGKIAWILGVHSKISSLNKRKSSGFAFDPSVNYSKVYSRYRPQYGYWVIGLQNTCEYNA
  FEDSSSSDPKVLTLFMAVPPCRIGVFLDYEAGIVSFFNVTNHGALIYKFSGCRFSRPAYP
  YFNPWNCLVPMTVCPPSS
• Function: Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity. Restricts the replication of many viruses including HIV-1, encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Zika virus (ZIKV). Mechanistically, negatively regulates HCV replication by promoting ubiquitination and subsequent degradation of viral NS5A. Acts also by promoting the degradation of Zika virus NS1 and NS3 proteins through proteasomal degradation. Acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter. Plays also a role in antiviral immunity by co-regulating together with NT5C2 the RIGI/NF-kappa-B pathway by promoting 'Lys-63'-linked ubiquitination of RIGI, while NT5C2 is responsible for 'Lys-48'-linked ubiquitination of RIGI. Participates in adaptive immunity by suppressing the amount of MHC class II protein in a negative feedback manner in order to limit the extent of MHC class II induction.
• Tissue Specificity: Strongly expressed in peripheral blood leukocytes, spleen, thymus, and ovary. Expressed at basal levels in other tissues.
• Reactome Pathway: Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Altered Expression	[1]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[2]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[3]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[8]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[10]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[10]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[10]
HIV infectious disease	DISO97HC	moderate	Biomarker	[11]
Neoplasm	DISZKGEW	Disputed	Biomarker	[12]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[13]
Inflammatory bowel disease	DISGN23E	Limited	Autosomal recessive	[14]

31 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[25]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[27]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[28]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[29]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[30]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[31]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[25]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[32]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[33]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[34]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[35]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[35]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[37]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[38]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[40]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[44]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[39]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of E3 ubiquitin-protein ligase TRIM22 (TRIM22).	[41]

References

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