Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH5KF2D)

• DOT Name: Receptor-type tyrosine-protein phosphatase F (PTPRF)
• Synonyms: EC 3.1.3.48; Leukocyte common antigen related; LAR
• Gene Name: PTPRF
• Related Disease:
  Acromegaly
  Cone-rod dystrophy 2
  Neuroblastoma
  Type-1/2 diabetes
  Adenocarcinoma
  Adenoma
  Adult glioblastoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Attention deficit hyperactivity disorder
  Autism
  Breast cancer
  Breast carcinoma
  Breasts and/or nipples, aplasia or hypoplasia of, 2
  Carcinoid syndrome
  Carcinoma
  Chronic renal failure
  Crohn disease
  Desmoid tumour
  End-stage renal disease
  Gastric adenocarcinoma
  Gastric cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Hereditary diffuse gastric adenocarcinoma
  Isolated congenital breast hypoplasia/aplasia
  Malignant mesothelioma
  Medullary thyroid gland carcinoma
  Neuroendocrine neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Pheochromocytoma
  Rectal carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Triple negative breast cancer
  Uveitis
  Melanoma
  Metastatic malignant neoplasm
  Stroke
  Autosomal dominant polycystic kidney disease
  Digestive system neoplasm
  Schizophrenia
• UniProt ID: PTPRF_HUMAN
• PDB ID: 1LAR; 2DJU; 2DN7; 2EDX; 2EDY; 2YD5; 2YD8; 4N5U; 6KR4; 6TPT; 6TPU; 6TPV; 6TPW
• EC Number: 3.1.3.48
• Pfam ID: PF00041 ; PF07679 ; PF00102
• Sequence:
  MAPEPAPGRTMVPLVPALVMLGLVAGAHGDSKPVFIKVPEDQTGLSGGVASFVCQATGEP
  KPRITWMKKGKKVSSQRFEVIEFDDGAGSVLRIQPLRVQRDEAIYECTATNSLGEINTSA
  KLSVLEEEQLPPGFPSIDMGPQLKVVEKARTATMLCAAGGNPDPEISWFKDFLPVDPATS
  NGRIKQLRSGALQIESSEESDQGKYECVATNSAGTRYSAPANLYVRVRRVAPRFSIPPSS
  QEVMPGGSVNLTCVAVGAPMPYVKWMMGAEELTKEDEMPVGRNVLELSNVVRSANYTCVA
  ISSLGMIEATAQVTVKALPKPPIDLVVTETTATSVTLTWDSGNSEPVTYYGIQYRAAGTE
  GPFQEVDGVATTRYSIGGLSPFSEYAFRVLAVNSIGRGPPSEAVRARTGEQAPSSPPRRV
  QARMLSASTMLVQWEPPEEPNGLVRGYRVYYTPDSRRPPNAWHKHNTDAGLLTTVGSLLP
  GITYSLRVLAFTAVGDGPPSPTIQVKTQQGVPAQPADFQAEVESDTRIQLSWLLPPQERI
  IMYELVYWAAEDEDQQHKVTFDPTSSYTLEDLKPDTLYRFQLAARSDMGVGVFTPTIEAR
  TAQSTPSAPPQKVMCVSMGSTTVRVSWVPPPADSRNGVITQYSVAYEAVDGEDRGRHVVD
  GISREHSSWDLVGLEKWTEYRVWVRAHTDVGPGPESSPVLVRTDEDVPSGPPRKVEVEPL
  NSTAVHVYWKLPVPSKQHGQIRGYQVTYVRLENGEPRGLPIIQDVMLAEAQWRPEESEDY
  ETTISGLTPETTYSVTVAAYTTKGDGARSKPKIVTTTGAVPGRPTMMISTTAMNTALLQW
  HPPKELPGELLGYRLQYCRADEARPNTIDFGKDDQHFTVTGLHKGTTYIFRLAAKNRAGL
  GEEFEKEIRTPEDLPSGFPQNLHVTGLTTSTTELAWDPPVLAERNGRIISYTVVFRDINS
  QQELQNITTDTRFTLTGLKPDTTYDIKVRAWTSKGSGPLSPSIQSRTMPVEQVFAKNFRV
  AAAMKTSVLLSWEVPDSYKSAVPFKILYNGQSVEVDGHSMRKLIADLQPNTEYSFVLMNR
  GSSAGGLQHLVSIRTAPDLLPHKPLPASAYIEDGRFDLSMPHVQDPSLVRWFYIVVVPID
  RVGGSMLTPRWSTPEELELDELLEAIEQGGEEQRRRRRQAERLKPYVAAQLDVLPETFTL
  GDKKNYRGFYNRPLSPDLSYQCFVLASLKEPMDQKRYASSPYSDEIVVQVTPAQQQEEPE
  MLWVTGPVLAVILIILIVIAILLFKRKRTHSPSSKDEQSIGLKDSLLAHSSDPVEMRRLN
  YQTPGMRDHPPIPITDLADNIERLKANDGLKFSQEYESIDPGQQFTWENSNLEVNKPKNR
  YANVIAYDHSRVILTSIDGVPGSDYINANYIDGYRKQNAYIATQGPLPETMGDFWRMVWE
  QRTATVVMMTRLEEKSRVKCDQYWPARGTETCGLIQVTLLDTVELATYTVRTFALHKSGS
  SEKRELRQFQFMAWPDHGVPEYPTPILAFLRRVKACNPLDAGPMVVHCSAGVGRTGCFIV
  IDAMLERMKHEKTVDIYGHVTCMRSQRNYMVQTEDQYVFIHEALLEAATCGHTEVPARNL
  YAHIQKLGQVPPGESVTAMELEFKLLASSKAHTSRFISANLPCNKFKNRLVNIMPYELTR
  VCLQPIRGVEGSDYINASFLDGYRQQKAYIATQGPLAESTEDFWRMLWEHNSTIIVMLTK
  LREMGREKCHQYWPAERSARYQYFVVDPMAEYNMPQYILREFKVTDARDGQSRTIRQFQF
  TDWPEQGVPKTGEGFIDFIGQVHKTKEQFGQDGPITVHCSAGVGRTGVFITLSIVLERMR
  YEGVVDMFQTVKTLRTQRPAMVQTEDQYQLCYRAALEYLGSFDHYAT
• Function: Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity.; The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Adherens junction (hsa04520)
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)
• Reactome Pathway:
  Insulin receptor recycling (R-HSA-77387)
  Synaptic adhesion-like molecules (R-HSA-8849932)
  Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acromegaly	DISCC73U	Definitive	Biomarker	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[2]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Adenoma	DIS78ZEV	Strong	Altered Expression	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[9]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[9]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[10]
Autism	DISV4V1Z	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[12]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[12]
Breasts and/or nipples, aplasia or hypoplasia of, 2	DIS6UNP1	Strong	Autosomal recessive	[13]
Carcinoid syndrome	DISDS5OT	Strong	Biomarker	[14]
Carcinoma	DISH9F1N	Strong	Altered Expression	[15]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[16]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[17]
Desmoid tumour	DISGX357	Strong	Altered Expression	[18]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[16]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[19]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[19]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[19]
Isolated congenital breast hypoplasia/aplasia	DIS9ODKJ	Strong	GermlineCausalMutation	[20]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[21]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[22]
Neuroendocrine neoplasm	DISNPLOO	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Obesity	DIS47Y1K	Strong	Genetic Variation	[26]
Osteoporosis	DISF2JE0	Strong	Biomarker	[27]
Pheochromocytoma	DIS56IFV	Strong	Genetic Variation	[28]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[29]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[30]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[30]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[30]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[31]
Uveitis	DISV0RYS	Strong	Altered Expression	[32]
Melanoma	DIS1RRCY	moderate	Altered Expression	[33]
Metastatic malignant neoplasm	DIS86UK6	moderate	Genetic Variation	[34]
Stroke	DISX6UHX	moderate	Genetic Variation	[35]
Autosomal dominant polycystic kidney disease	DISBHWUI	Limited	Biomarker	[16]
Digestive system neoplasm	DISPOJCT	Limited	Biomarker	[36]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[47]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[48]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[40]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[54]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[55]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[56]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[57]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[58]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[51]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Receptor-type tyrosine-protein phosphatase F (PTPRF).	[51]

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