Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPGHZB9)

• DOT Name: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)
• Synonyms: IFIT-3; CIG49; ISG-60; Interferon-induced 60 kDa protein; IFI-60K; Interferon-induced protein with tetratricopeptide repeats 4; IFIT-4; Retinoic acid-induced gene G protein; P60; RIG-G
• Gene Name: IFIT3
• Related Disease:
  Alzheimer disease
  Autoimmune disease
  Breast neoplasm
  Choriocarcinoma
  Influenza
  Leukopenia
  Listeriosis
  Lyme disease
  Major depressive disorder
  Pancreatic adenocarcinoma
  Pancreatic cancer
  Periventricular leukomalacia
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Vasculitis
  Chronic graft versus host disease
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Metastatic malignant neoplasm
  Advanced cancer
  Ankylosing spondylitis
  Cystitis
  Hereditary hemochromatosis
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic ductal carcinoma
• UniProt ID: IFIT3_HUMAN
• PDB ID: 6C6K
• Pfam ID: PF13424 ; PF13176 ; PF13181
• Sequence:
  MSEVTKNSLEKILPQLKCHFTWNLFKEDSVSRDLEDRVCNQIEFLNTEFKATMYNLLAYI
  KHLDGNNEAALECLRQAEELIQQEHADQAEIRSLVTWGNYAWVYYHLGRLSDAQIYVDKV
  KQTCKKFSNPYSIEYSELDCEEGWTQLKCGRNERAKVCFEKALEEKPNNPEFSSGLAIAM
  YHLDNHPEKQFSTDVLKQAIELSPDNQYVKVLLGLKLQKMNKEAEGEQFVEEALEKSPCQ
  TDVLRSAAKFYRRKGDLDKAIELFQRVLESTPNNGYLYHQIGCCYKAKVRQMQNTGESEA
  SGNKEMIEALKQYAMDYSNKALEKGLNPLNAYSDLAEFLETECYQTPFNKEVPDAEKQQS
  HQRYCNLQKYNGKSEDTAVQHGLEGLSISKKSTDKEEIKDQPQNVSENLLPQNAPNYWYL
  QGLIHKQNGDLLQAAKCYEKELGRLLRDAPSGIGSIFLSASELEDGSEEMGQGAVSSSPR
  ELLSNSEQLN
• Function: IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exhibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Up-regulates CDKN1A/p21 by down-regulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2.
• Tissue Specificity: Expression significantly higher in peripheral blood mononuclear cells (PBMCs) and monocytes from systemic lupus erythematosus (SLE) patients than in those from healthy individuals (at protein level). Spleen, lung, leukocytes, lymph nodes, placenta, bone marrow and fetal liver.
• Reactome Pathway: Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Choriocarcinoma	DISDBVNL	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Leukopenia	DISJMBMM	Strong	Altered Expression	[2]
Listeriosis	DISKMQBM	Strong	Biomarker	[6]
Lyme disease	DISO70G5	Strong	Genetic Variation	[7]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[8]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[10]
Periventricular leukomalacia	DIS152XL	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[14]
Vasculitis	DISQRKDX	Strong	Biomarker	[15]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[17]
leukaemia	DISS7D1V	moderate	Altered Expression	[18]
Leukemia	DISNAKFL	moderate	Altered Expression	[18]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[19]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[13]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[20]
Cystitis	DIS2D4B9	Limited	Biomarker	[21]
Hereditary hemochromatosis	DISVG5MT	Limited	Biomarker	[22]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Altered Expression	[13]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[10]

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 Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[28]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[31]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[32]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[33]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[34]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[35]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[36]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[37]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[33]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[38]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[33]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[39]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[33]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[33]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[40]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[42]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[43]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[48]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[49]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3).	[47]

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