Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAP5AT3)

• DOT Name: Receptor-type tyrosine-protein phosphatase kappa (PTPRK)
• Synonyms: Protein-tyrosine phosphatase kappa; R-PTP-kappa; EC 3.1.3.48
• Gene Name: PTPRK
• Related Disease:
  Advanced cancer
  Central nervous system lymphoma
  Coeliac disease
  Colorectal carcinoma
  Head-neck squamous cell carcinoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Prostate neoplasm
  Rheumatoid arthritis
  T-cell lymphoma
  Lung cancer
  Asthma
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PTPRK_HUMAN
• PDB ID: 2C7S; 8A1F
• EC Number: 3.1.3.48
• Pfam ID: PF00041 ; PF07679 ; PF00629 ; PF00102
• Sequence:
  MDTTAAAALPAFVALLLLSPWPLLGSAQGQFSAGGCTFDDGPGACDYHQDLYDDFEWVHV
  SAQEPHYLPPEMPQGSYMIVDSSDHDPGEKARLQLPTMKENDTHCIDFSYLLYSQKGLNP
  GTLNILVRVNKGPLANPIWNVTGFTGRDWLRAELAVSTFWPNEYQVIFEAEVSGGRSGYI
  AIDDIQVLSYPCDKSPHFLRLGDVEVNAGQNATFQCIATGRDAVHNKLWLQRRNGEDIPV
  AQTKNINHRRFAASFRLQEVTKTDQDLYRCVTQSERGSGVSNFAQLIVREPPRPIAPPQL
  LGVGPTYLLIQLNANSIIGDGPIILKEVEYRMTSGSWTETHAVNAPTYKLWHLDPDTEYE
  IRVLLTRPGEGGTGLPGPPLITRTKCAEPMRTPKTLKIAEIQARRIAVDWESLGYNITRC
  HTFNVTICYHYFRGHNESKADCLDMDPKAPQHVVNHLPPYTNVSLKMILTNPEGRKESEE
  TIIQTDEDVPGPVPVKSLQGTSFENKIFLNWKEPLDPNGIITQYEISYSSIRSFDPAVPV
  AGPPQTVSNLWNSTHHVFMHLHPGTTYQFFIRASTVKGFGPATAINVTTNISAPTLPDYE
  GVDASLNETATTITVLLRPAQAKGAPISAYQIVVEELHPHRTKREAGAMECYQVPVTYQN
  AMSGGAPYYFAAELPPGNLPEPAPFTVGDNRTYQGFWNPPLAPRKGYNIYFQAMSSVEKE
  TKTQCVRIATKAATEEPEVIPDPAKQTDRVVKIAGISAGILVFILLLLVVILIVKKSKLA
  KKRKDAMGNTRQEMTHMVNAMDRSYADQSTLHAEDPLSITFMDQHNFSPRYENHSATAES
  SRLLDVPRYLCEGTESPYQTGQLHPAIRVADLLQHINLMKTSDSYGFKEEYESFFEGQSA
  SWDVAKKDQNRAKNRYGNIIAYDHSRVILQPVEDDPSSDYINANYIDGYQRPSHYIATQG
  PVHETVYDFWRMIWQEQSACIVMVTNLVEVGRVKCYKYWPDDTEVYGDFKVTCVEMEPLA
  EYVVRTFTLERRGYNEIREVKQFHFTGWPDHGVPYHATGLLSFIRRVKLSNPPSAGPIVV
  HCSAGAGRTGCYIVIDIMLDMAEREGVVDIYNCVKALRSRRINMVQTEEQYIFIHDAILE
  ACLCGETAIPVCEFKAAYFDMIRIDSQTNSSHLKDEFQTLNSVTPRLQAEDCSIACLPRN
  HDKNRFMDMLPPDRCLPFLITIDGESSNYINAALMDSYRQPAAFIVTQYPLPNTVKDFWR
  LVYDYGCTSIVMLNEVDLSQGCPQYWPEEGMLRYGPIQVECMSCSMDCDVINRIFRICNL
  TRPQEGYLMVQQFQYLGWASHREVPGSKRSFLKLILQVEKWQEECEEGEGRTIIHCLNGG
  GRSGMFCAIGIVVEMVKRQNVVDVFHAVKTLRNSKPNMVEAPEQYRFCYDVALEYLESS
• Function: Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis. Negative regulator of EGFR signaling pathway. Forms complexes with beta-catenin and gamma-catenin/plakoglobin. Beta-catenin may be a substrate for the catalytic activity of PTPRK/PTP-kappa.
• Tissue Specificity: High levels in lung, brain and colon; less in liver, pancreas, stomach, kidney, placenta and mammary carcinoma.
• Reactome Pathway: EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Central nervous system lymphoma	DISBYQTA	Strong	Biomarker	[2]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[7]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[8]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[8]
T-cell lymphoma	DISSXRTQ	Strong	Posttranslational Modification	[10]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[11]
Asthma	DISW9QNS	Limited	Genetic Variation	[12]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[13]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[13]
Prostate cancer	DISF190Y	Limited	Altered Expression	[14]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[14]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Receptor-type tyrosine-protein phosphatase kappa (PTPRK) affects the response to substance of Fluorouracil.	[39]
Topotecan	DMP6G8T	Approved	Receptor-type tyrosine-protein phosphatase kappa (PTPRK) affects the response to substance of Topotecan.	[39]

22 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 Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[20]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[22]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[24]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[26]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[34]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[35]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[36]
GW7647	DM9RD0C	Investigative	GW7647 decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[37]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Receptor-type tyrosine-protein phosphatase kappa (PTPRK).	[30]

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