Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK5T6HZ)

• DOT Name: Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2)
• Synonyms: NF-ATc2; NFATc2; NFAT pre-existing subunit; NF-ATp; T-cell transcription factor NFAT1
• Gene Name: NFATC2
• Related Disease:
  Melanoma
  Adult glioblastoma
  Alzheimer disease
  Breast neoplasm
  Cardiac failure
  Cardiovascular disease
  Colon cancer
  Colorectal carcinoma
  Congestive heart failure
  Esophageal squamous cell carcinoma
  Ewing sarcoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  High blood pressure
  Leukemia
  Lung adenocarcinoma
  Malignant soft tissue neoplasm
  Metastatic malignant neoplasm
  Multiple sclerosis
  Narcolepsy
  Nervous system disease
  Neuroblastoma
  Non-insulin dependent diabetes
  Osteoarthritis
  Pancreatic cancer
  Pneumonia
  Pneumonitis
  Pulmonary hypertension
  Sarcoma
  Schizophrenia
  Soft tissue neoplasm
  Systemic lupus erythematosus
  Acute myelogenous leukaemia
  Advanced cancer
  Allergic rhinitis
  Varicose veins
  Colitis
  Congenital heart disease
  Asthma
  Autoimmune disease
  Colon carcinoma
  Glioma
  Joint contractures, osteochondromas, and B-cell lymphoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Metastatic melanoma
  Rheumatoid arthritis
• UniProt ID: NFAC2_HUMAN
• PDB ID: 1A02; 1OWR; 1P7H; 1PZU; 1S9K; 2AS5; 2O93; 3QRF; 8OW4
• Pfam ID: PF16179 ; PF00554
• Sequence:
  MNAPERQPQPDGGDAPGHEPGGSPQDELDFSILFDYEYLNPNEEEPNAHKVASPPSGPAY
  PDDVLDYGLKPYSPLASLSGEPPGRFGEPDRVGPQKFLSAAKPAGASGLSPRIEITPSHE
  LIQAVGPLRMRDAGLLVEQPPLAGVAASPRFTLPVPGFEGYREPLCLSPASSGSSASFIS
  DTFSPYTSPCVSPNNGGPDDLCPQFQNIPAHYSPRTSPIMSPRTSLAEDSCLGRHSPVPR
  PASRSSSPGAKRRHSCAEALVALPPGASPQRSRSPSPQPSSHVAPQDHGSPAGYPPVAGS
  AVIMDALNSLATDSPCGIPPKMWKTSPDPSPVSAAPSKAGLPRHIYPAVEFLGPCEQGER
  RNSAPESILLVPPTWPKPLVPAIPICSIPVTASLPPLEWPLSSQSGSYELRIEVQPKPHH
  RAHYETEGSRGAVKAPTGGHPVVQLHGYMENKPLGLQIFIGTADERILKPHAFYQVHRIT
  GKTVTTTSYEKIVGNTKVLEIPLEPKNNMRATIDCAGILKLRNADIELRKGETDIGRKNT
  RVRLVFRVHIPESSGRIVSLQTASNPIECSQRSAHELPMVERQDTDSCLVYGGQQMILTG
  QNFTSESKVVFTEKTTDGQQIWEMEATVDKDKSQPNMLFVEIPEYRNKHIRTPVKVNFYV
  INGKRKRSQPQHFTYHPVPAIKTEPTDEYDPTLICSPTHGGLGSQPYYPQHPMVAESPSC
  LVATMAPCQQFRTGLSSPDARYQQQNPAAVLYQRSKSLSPSLLGYQQPALMAAPLSLADA
  HRSVLVHAGSQGQSSALLHPSPTNQQASPVIHYSPTNQQLRCGSHQEFQHIMYCENFAPG
  TTRPGPPPVSQGQRLSPGSYPTVIQQQNATSQRAAKNGPPVSDQKEVLPAGVTIKQEQNL
  DQTYLDDVNEIIRKEFSGPPARNQT
• Function: Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. Is involved in the negative regulation of chondrogenesis.
• Tissue Specificity: Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas. Isoform 1 is highly expressed in the small intestine, heart, testis, prostate, thymus, placenta and thyroid. Isoform 3 is highly expressed in stomach, uterus, placenta, trachea and thyroid.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Efferocytosis (hsa04148)
  Cellular senescence (hsa04218)
  Wnt sig.ling pathway (hsa04310)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  C-type lectin receptor sig.ling pathway (hsa04625)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  Oxytocin sig.ling pathway (hsa04921)
  Yersinia infection (hsa05135)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  CLEC7A (Dectin-1) induces NFAT activation (R-HSA-5607763)
  RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330)
  Calcineurin activates NFAT (R-HSA-2025928)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Ewing sarcoma	DISQYLV3	Strong	Genetic Variation	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[17]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[18]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[20]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[23]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[24]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[24]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[25]
Sarcoma	DISZDG3U	Strong	Biomarker	[10]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[26]
Soft tissue neoplasm	DISP2OHE	Strong	Genetic Variation	[10]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[28]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[29]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[30]
Varicose veins	DISIMBN2	moderate	Genetic Variation	[31]
Colitis	DISAF7DD	Disputed	Biomarker	[7]
Congenital heart disease	DISQBA23	Disputed	Autosomal dominant	[32]
Asthma	DISW9QNS	Limited	Biomarker	[33]
Autoimmune disease	DISORMTM	Limited	Biomarker	[27]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[7]
Glioma	DIS5RPEH	Limited	Biomarker	[11]
Joint contractures, osteochondromas, and B-cell lymphoma	DISPH8MQ	Limited	Unknown	[34]
Lung cancer	DISCM4YA	Limited	Biomarker	[35]
Lung carcinoma	DISTR26C	Limited	Biomarker	[35]
Lymphoma	DISN6V4S	Limited	Altered Expression	[36]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[37]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[38]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) affects the response to substance of Rosiglitazone.	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[51]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[53]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[41]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[42]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[45]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[46]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[47]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[49]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[50]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[52]
AM-404	DMBK9PS	Investigative	AM-404 decreases the activity of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[56]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine affects the localization of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[48]
Harmine	DMPA5WD	Patented	Harmine affects the localization of Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2).	[54]

References

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