Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4TMERS)

• DOT Name: Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)
• Synonyms: NF-ATc1; NFATc1; NFAT transcription complex cytosolic component; NF-ATc; NFATc
• Gene Name: NFATC1
• Related Disease:
  Chronic renal failure
  Matthew-Wood syndrome
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Ankylosing spondylitis
  Arthritis
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cardiac disease
  Cherubism
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Glioma
  Hepatocellular carcinoma
  Hypothyroidism
  Inflammatory bowel disease
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Periodontitis
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Renal cell carcinoma
  Rheumatoid arthritis
  Type-1/2 diabetes
  Ulcerative colitis
  Urinary bladder neoplasm
  Lymphoma
  Melanoma
  Small lymphocytic lymphoma
  Congenital heart disease
  Adult glioblastoma
  Advanced cancer
  Crohn disease
  Glioblastoma multiforme
  Non-insulin dependent diabetes
  Osteoporosis
  Ovarian neoplasm
  Pancreatic cancer
  Sclerosing cholangitis
• UniProt ID: NFAC1_HUMAN
• PDB ID: 1A66; 1NFA; 5SVE
• Pfam ID: PF16179 ; PF00554
• Sequence:
  MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEEEHYGYASSNVSPALPLPT
  AHSTLPAPCHNLQTSTPGIIPPADHPSGYGAALDGGPAGYFLSSGHTRPDGAPALESPRI
  EITSCLGLYHNNNQFFHDVEVEDVLPSSKRSPSTATLSLPSLEAYRDPSCLSPASSLSSR
  SCNSEASSYESNYSYPYASPQTSPWQSPCVSPKTTDPEEGFPRGLGACTLLGSPRHSPST
  SPRASVTEESWLGARSSRPASPCNKRKYSLNGRQPPYSPHHSPTPSPHGSPRVSVTDDSW
  LGNTTQYTSSAIVAAINALTTDSSLDLGDGVPVKSRKTTLEQPPSVALKVEPVGEDLGSP
  PPPADFAPEDYSSFQHIRKGGFCDQYLAVPQHPYQWAKPKPLSPTSYMSPTLPALDWQLP
  SHSGPYELRIEVQPKSHHRAHYETEGSRGAVKASAGGHPIVQLHGYLENEPLMLQLFIGT
  ADDRLLRPHAFYQVHRITGKTVSTTSHEAILSNTKVLEIPLLPENSMRAVIDCAGILKLR
  NSDIELRKGETDIGRKNTRVRLVFRVHVPQPSGRTLSLQVASNPIECSQRSAQELPLVEK
  QSTDSYPVVGGKKMVLSGHNFLQDSKVIFVEKAPDGHHVWEMEAKTDRDLCKPNSLVVEI
  PPFRNQRITSPVHVSFYVCNGKRKRSQYQRFTYLPANVPIIKTEPTDDYEPAPTCGPVSQ
  GLSPLPRPYYSQQLAMPPDPSSCLVAGFPPCPQRSTLMPAAPGVSPKLHDLSPAAYTKGV
  ASPGHCHLGLPQPAGEAPAVQDVPRPVATHPGSPGQPPPALLPQQVSAPPSSSCPPGLEH
  SLCPSSPSPPLPPATQEPTCLQPCSPACPPATGRPQHLPSTVRRDESPTAGPRLLPEVHE
  DGSPNLAPIPVTVKREPEELDQLYLDDVNEIIRNDLSSTSTHS
• Function: Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells. Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function.
• Tissue Specificity: Expressed in thymus, peripheral leukocytes as T-cells and spleen. Isoforms A are preferentially expressed in effector T-cells (thymus and peripheral leukocytes) whereas isoforms B and isoforms C are preferentially expressed in naive T-cells (spleen). Isoforms B are expressed in naive T-cells after first antigen exposure and isoforms A are expressed in effector T-cells after second antigen exposure. Isoforms IA are widely expressed but not detected in liver nor pancreas, neural expression is strongest in corpus callosum. Isoforms IB are expressed mostly in muscle, cerebellum, placenta and thymus, neural expression in fetal and adult brain, strongest in corpus callosum.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Efferocytosis (hsa04148)
  Cellular senescence (hsa04218)
  Wnt sig.ling pathway (hsa04310)
  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)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  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)
  Inflammatory bowel disease (hsa05321)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  Ca2+ pathway (R-HSA-4086398)
  CLEC7A (Dectin-1) induces NFAT activation (R-HSA-5607763)
  Calcineurin activates NFAT (R-HSA-2025928)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Ankylosing spondylitis	DISRC6IR	Strong	Biomarker	[4]
Arthritis	DIST1YEL	Strong	Altered Expression	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Biomarker	[9]
Cardiac disease	DISVO1I5	Strong	Biomarker	[10]
Cherubism	DISHLJI0	Strong	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[18]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[20]
Lung neoplasm	DISVARNB	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[23]
Periodontitis	DISI9JOI	Strong	Altered Expression	[24]
Prostate cancer	DISF190Y	Strong	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[25]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[28]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[26]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[9]
Lymphoma	DISN6V4S	moderate	Biomarker	[29]
Melanoma	DIS1RRCY	moderate	Biomarker	[30]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[31]
Congenital heart disease	DISQBA23	Disputed	Autosomal dominant	[32]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[33]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[34]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[26]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[33]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[35]
Osteoporosis	DISF2JE0	Limited	Biomarker	[36]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[23]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[37]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[26]

4 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 1 (NFATC1).	[38]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[44]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[45]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[46]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[47]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine affects the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[48]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[53]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[54]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Harmine	DMPA5WD	Patented	Harmine affects the localization of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).	[51]

References

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