Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0BGA27)

• DOT Name: Histone-lysine N-methyltransferase PRDM16 (PRDM16)
• Synonyms: EC 2.1.1.367; PR domain zinc finger protein 16; PR domain-containing protein 16; Transcription factor MEL1; MDS1/EVI1-like gene 1
• Gene Name: PRDM16
• Related Disease:
  Bone disease
  Cardiomyopathy
  leukaemia
  Myelodysplastic syndrome
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Acute myelomonocytic leukemia M4
  Adult T-cell leukemia/lymphoma
  Astrocytoma
  Cardiac failure
  Cardiovascular disease
  Chronic granulomatous disease
  Congestive heart failure
  Coronary heart disease
  Diabetic retinopathy
  Dilated cardiomyopathy 1A
  Familial dilated cardiomyopathy
  Fatty liver disease
  Hydrocephalus
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Migraine with aura
  Motion sickness
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Primary biliary cholangitis
  Retinoblastoma
  Rheumatoid arthritis
  T-cell acute lymphoblastic leukaemia
  Allergic rhinitis
  Cutaneous melanoma
  Left ventricular noncompaction 8
  Myotonic dystrophy type 2
  Left ventricular noncompaction
  Obsolete familial isolated dilated cardiomyopathy
  Advanced cancer
  Dilated cardiomyopathy
  Gastric cancer
  Melanoma
  Myeloid leukaemia
  Stomach cancer
  Type-1/2 diabetes
• UniProt ID: PRD16_HUMAN
• PDB ID: 2N1I; 6BW4
• EC Number: 2.1.1.367
• Pfam ID: PF21549 ; PF00096 ; PF13912
• Sequence:
  MRSKARARKLAKSDGDVVNNMYEPNRDLLASHSAEDEAEDSAMSPIPVGPPSPFPTSEDF
  TPKEGSPYEAPVYIPEDIPIPADFELRESSIPGAGLGVWAKRKMEAGERLGPCVVVPRAA
  AKETDFGWEQILTDVEVSPQEGCITKISEDLGSEKFCVDANQAGAGSWLKYIRVACSCDD
  QNLTMCQISEQIYYKVIKDIEPGEELLVHVKEGVYPLGTVPPGLDEEPTFRCDECDELFQ
  SKLDLRRHKKYTCGSVGAALYEGLAEELKPEGLGGGSGQAHECKDCERMFPNKYSLEQHM
  VIHTEEREYKCDQCPKAFNWKSNLIRHQMSHDSGKRFECENCVKVFTDPSNLQRHIRSQH
  VGARAHACPDCGKTFATSSGLKQHKHIHSTVKPFICEVCHKSYTQFSNLCRHKRMHADCR
  TQIKCKDCGQMFSTTSSLNKHRRFCEGKNHYTPGGIFAPGLPLTPSPMMDKAKPSPSLNH
  ASLGFNEYFPSRPHPGSLPFSTAPPTFPALTPGFPGIFPPSLYPRPPLLPPTSLLKSPLN
  HTQDAKLPSPLGNPALPLVSAVSNSSQGTTAAAGPEEKFESRLEDSCVEKLKTRSSDMSD
  GSDFEDVNTTTGTDLDTTTGTGSDLDSDVDSDPDKDKGKGKSAEGQPKFGGGLAPPGAPN
  SVAEVPVFYSQHSFFPPPDEQLLTATGAAGDSIKAIASIAEKYFGPGFMGMQEKKLGSLP
  YHSAFPFQFLPNFPHSLYPFTDRALAHNLLVKAEPKSPRDALKVGGPSAECPFDLTTKPK
  DVKPILPMPKGPSAPASGEEQPLDLSIGSRARASQNGGGREPRKNHVYGERKLGAGEGLP
  QVCPARMPQQPPLHYAKPSPFFMDPIYSRVEKRKVTDPVGALKEKYLRPSPLLFHPQMSA
  IETMTEKLESFAAMKADSGSSLQPLPHHPFNFRSPPPTLSDPILRKGKERYTCRYCGKIF
  PRSANLTRHLRTHTGEQPYRCKYCDRSFSISSNLQRHVRNIHNKEKPFKCHLCNRCFGQQ
  TNLDRHLKKHEHENAPVSQHPGVLTNHLGTSASSPTSESDNHALLDEKEDSYFSEIRNFI
  ANSEMNQASTRTEKRADMQIVDGSAQCPGLASEKQEDVEEEDDDDLEEDDEDSLAGKSQD
  DTVSPAPEPQAAYEDEEDEEPAASLAVGFDHTRRCAEDHEGGLLALEPMPTFGKGLDLRR
  AAEEAFEVKDVLNSTLDSEALKHTLCRQAKNQAYAMMLSLSEDTPLHTPSQGSLDAWLKV
  TGATSESGAFHPINHL
• Function: Binds DNA and functions as a transcriptional regulator. Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation. Likely to be one of the primary histone methyltransferases along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation. Functions in the differentiation of brown adipose tissue (BAT) which is specialized in dissipating chemical energy in the form of heat in response to cold or excess feeding while white adipose tissue (WAT) is specialized in the storage of excess energy and the control of systemic metabolism. Together with CEBPB, regulates the differentiation of myoblastic precursors into brown adipose cells. Functions as a repressor of TGF-beta signaling ; [Isoform 4]: Binds DNA and functions as a transcriptional regulator. Functions as a repressor of TGF-beta signaling. May regulate granulocyte differentiation.
• Tissue Specificity: Expressed in uterus and kidney. Expressed in both cardiomyocytes and interstitial cells.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
• Reactome Pathway: PKMTs methylate histone lysines (R-HSA-3214841)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone disease	DISE1F82	Definitive	Biomarker	[1]
Cardiomyopathy	DISUPZRG	Definitive	Biomarker	[2]
leukaemia	DISS7D1V	Definitive	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[4]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[6]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[7]
Astrocytoma	DISL3V18	Strong	Altered Expression	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[10]
Chronic granulomatous disease	DIS9ZR24	Strong	Altered Expression	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[13]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[14]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[14]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[15]
Hydrocephalus	DISIZUF7	Strong	Genetic Variation	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Migraine with aura	DISDM7I8	Strong	Genetic Variation	[18]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[9]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[20]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[21]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Altered Expression	[3]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[22]
Cutaneous melanoma	DIS3MMH9	moderate	Biomarker	[23]
Left ventricular noncompaction 8	DISXDNMV	Moderate	Autosomal dominant	[24]
Myotonic dystrophy type 2	DIS5ZWF1	moderate	Altered Expression	[25]
Left ventricular noncompaction	DISJ4QEG	Supportive	Autosomal dominant	[14]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Dilated cardiomyopathy	DISX608J	Limited	Autosomal dominant	[26]
Gastric cancer	DISXGOUK	Limited	Biomarker	[27]
Melanoma	DIS1RRCY	Limited	Biomarker	[28]
Myeloid leukaemia	DISMN944	Limited	Altered Expression	[29]
Stomach cancer	DISKIJSX	Limited	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Limited	Posttranslational Modification	[30]

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 Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[38]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[40]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl affects the methylation of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[47]

16 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 Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[37]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[41]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[42]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[35]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[35]
Tofacitinib	DMBS370	Approved	Tofacitinib increases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[43]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[44]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone-lysine N-methyltransferase PRDM16 (PRDM16).	[46]

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