Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5WA666)

• DOT Name: Tyrosine-protein phosphatase non-receptor type 12 (PTPN12)
• Synonyms: EC 3.1.3.48; PTP-PEST; Protein-tyrosine phosphatase G1; PTPG1
• Gene Name: PTPN12
• Related Disease:
  Hereditary leiomyomatosis and renal cell cancer
  Acute myocardial infarction
  Adult glioblastoma
  Autoimmune disease
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Disorder of orbital region
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Graves disease
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Pyogenic arthritis-pyoderma gangrenosum-acne syndrome
  Retinoblastoma
  Triple negative breast cancer
  Urinary bladder neoplasm
  Invasive breast carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: PTN12_HUMAN
• PDB ID: 5HDE; 5J8R; 5O2P
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MEQVEILRKFIQRVQAMKSPDHNGEDNFARDFMRLRRLSTKYRTEKIYPTATGEKEENVK
  KNRYKDILPFDHSRVKLTLKTPSQDSDYINANFIKGVYGPKAYVATQGPLANTVIDFWRM
  IWEYNVVIIVMACREFEMGRKKCERYWPLYGEDPITFAPFKISCEDEQARTDYFIRTLLL
  EFQNESRRLYQFHYVNWPDHDVPSSFDSILDMISLMRKYQEHEDVPICIHCSAGCGRTGA
  ICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQLFEKQLQL
  YEIHGAQKIADGVNEINTENMVSSIEPEKQDSPPPKPPRTRSCLVEGDAKEEILQPPEPH
  PVPPILTPSPPSAFPTVTTVWQDNDRYHPKPVLHMVSSEQHSADLNRNYSKSTELPGKNE
  STIEQIDKKLERNLSFEIKKVPLQEGPKSFDGNTLLNRGHAIKIKSASPCIADKISKPQE
  LSSDLNVGDTSQNSCVDCSVTQSNKVSVTPPEESQNSDTPPRPDRLPLDEKGHVTWSFHG
  PENAIPIPDLSEGNSSDINYQTRKTVSLTPSPTTQVETPDLVDHDNTSPLFRTPLSFTNP
  LHSDDSDSDERNSDGAVTQNKTNISTASATVSAATSTESISTRKVLPMSIARHNIAGTTH
  SGAEKDVDVSEDSPPPLPERTPESFVLASEHNTPVRSEWSELQSQERSEQKKSEGLITSE
  NEKCDHPAGGIHYEMCIECPPTFSDKREQISENPTEATDIGFGNRCGKPKGPRDPPSEWT
• Function: Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades. Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2. Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248'.
• Reactome Pathway:
  EGFR downregulation (R-HSA-182971)
  Signaling by PDGF (R-HSA-186797)
  Downregulation of ERBB2 signaling (R-HSA-8863795)
  Interleukin-37 signaling (R-HSA-9008059)
  Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary leiomyomatosis and renal cell cancer	DISN22G2	Definitive	Posttranslational Modification	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[7]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Graves disease	DISU4KOQ	Strong	Biomarker	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[13]
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	DIS7E15X	Strong	Biomarker	[14]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[15]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[16]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[17]
Invasive breast carcinoma	DISANYTW	Disputed	Biomarker	[18]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine	DMM2NSK	Approved	Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) increases the Apoptosis ADR of Adenosine.	[43]

5 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 Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[19]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[29]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[30]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[31]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[36]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[40]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[41]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Tyrosine-protein phosphatase non-receptor type 12 (PTPN12).	[42]

References

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