Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU6ZA7F)

• DOT Name: Activating transcription factor 7-interacting protein 1 (ATF7IP)
• Synonyms: ATF-interacting protein; ATF-IP; ATF7-interacting protein; ATFa-associated modulator; hAM; MBD1-containing chromatin-associated factor 1; P621
• Gene Name: ATF7IP
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Embryonal neoplasm
  Germ cell tumor
  T-cell acute lymphoblastic leukaemia
  Testicular cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Acute lymphocytic leukaemia
  Adenocarcinoma
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Autoimmune disease
  Bipolar disorder
  Cardiovascular disease
  Childhood acute lymphoblastic leukemia
  Classic Hodgkin lymphoma
  Cystic fibrosis
  Dementia
  Generalized anxiety disorder
  Hepatitis C virus infection
  Huntington disease
  Inflammation
  Inflammatory bowel disease
  leukaemia
  Leukemia
  Lymphoma
  Major depressive disorder
  Mood disorder
  Multiple sclerosis
  Myelodysplastic syndrome
  Myelopathy
  Neoplasm of testis
  Nervous system disease
  Non-insulin dependent diabetes
  Pediatric lymphoma
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Testicular germ cell tumor
  Uterine fibroids
  Chronic renal failure
  End-stage renal disease
  Neoplasm
  Schizophrenia
• UniProt ID: MCAF1_HUMAN
• PDB ID: 2RPQ
• Pfam ID: PF16788 ; PF16794
• Sequence:
  MDSLEEPQKKVFKARKTMRVSDRQQLEAVYKVKEELLKTDVKLLNGNHENGDLDPTSPLE
  NMDYIKDKEEVNGIEEICFDPEGSKAEWKETPCILSVNVKNKQDDDLNCEPLSPHNITPE
  PVSKLPAEPVSGDPAPGDLDAGDPASGVLASGDSTSGDPTSSEPSSSDAASGDATSGDAP
  SGDVSPGDATSGDATADDLSSGDPTSSDPIPGEPVPVEPISGDCAADDIASSEITSVDLA
  SGAPASTDPASDDLASGDLSSSELASDDLATGELASDELTSESTFDRTFEPKSVPVCEPV
  PEIDNIEPSSNKDDDFLEKNGADEKLEQIQSKDSLDEKNKADNNIDANEETLETDDTTIC
  SDRPPENEKKVEEDIITELALGEDAISSSMEIDQGEKNEDETSADLVETINENVIEDNKS
  ENILENTDSMETDEIIPILEKLAPSEDELTCFSKTSLLPIDETNPDLEEKMESSFGSPSK
  QESSESLPKEAFLVLSDEEDISGEKDESEVISQNETCSPAEVESNEKDNKPEEEEQVIHE
  DDERPSEKNEFSRRKRSKSEDMDNVQSKRRRYMEEEYEAEFQVKITAKGDINQKLQKVIQ
  WLLEEKLCALQCAVFDKTLAELKTRVEKIECNKRHKTVLTELQAKIARLTKRFEAAKEDL
  KKRHEHPPNPPVSPGKTVNDVNSNNNMSYRNAGTVRQMLESKRNVSESAPPSFQTPVNTV
  SSTNLVTPPAVVSSQPKLQTPVTSGSLTATSVLPAPNTATVVATTQVPSGNPQPTISLQP
  LPVILHVPVAVSSQPQLLQSHPGTLVTNQPSGNVEFISVQSPPTVSGLTKNPVSLPSLPN
  PTKPNNVPSVPSPSIQRNPTASAAPLGTTLAVQAVPTAHSIVQATRTSLPTVGPSGLYSP
  STNRGPIQMKIPISAFSTSSAAEQNSNTTPRIENQTNKTIDASVSKKAADSTSQCGKATG
  SDSSGVIDLTMDDEESGASQDPKKLNHTPVSTMSSSQPVSRPLQPIQPAPPLQPSGVPTS
  GPSQTTIHLLPTAPTTVNVTHRPVTQVTTRLPVPRAPANHQVVYTTLPAPPAQAPLRGTV
  MQAPAVRQVNPQNSVTVRVPQTTTYVVNNGLTLGSTGPQLTVHHRPPQVHTEPPRPVHPA
  PLPEAPQPQRLPPEAASTSLPQKPHLKLARVQSQNGIVLSWSVLEVDRSCATVDSYHLYA
  YHEEPSATVPSQWKKIGEVKALPLPMACTLTQFVSGSKYYFAVRAKDIYGRFGPFCDPQS
  TDVISSTQSS
• Function: Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Required for HUSH-mediated heterochromatin formation and gene silencing. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. Stabilizes SETDB1, is required to stimulate histone methyltransferase activity of SETDB1 and facilitates the conversion of dimethylated to trimethylated H3 'Lys-9' (H3K9me3). The complex formed with MBD1 and SETDB1 represses transcription and couples DNA methylation and histone H3 'Lys-9' trimethylation (H3K9me3). Facilitates telomerase TERT and TERC gene expression by SP1 in cancer cells.
• Tissue Specificity: Detected at low levels in breast, lung and stomach; highly up-regulated in the corresponding cancerous tissues (at protein level).
• Reactome Pathway: PKMTs methylate histone lysines (R-HSA-3214841)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[2]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Embryonal neoplasm	DIS5MQSB	Definitive	Biomarker	[3]
Germ cell tumor	DIS62070	Definitive	Biomarker	[3]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[4]
Testicular cancer	DIS6HNYO	Definitive	Biomarker	[3]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Biomarker	[5]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[5]
Thyroid tumor	DISLVKMD	Definitive	Biomarker	[5]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[7]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Alzheimer disease	DISF8S70	Strong	Biomarker	[10]
Anxiety	DISIJDBA	Strong	Genetic Variation	[11]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[11]
Autoimmune disease	DISORMTM	Strong	Biomarker	[12]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[13]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[14]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[15]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[16]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[17]
Dementia	DISXL1WY	Strong	Biomarker	[18]
Generalized anxiety disorder	DISPSQCW	Strong	Biomarker	[19]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[20]
Huntington disease	DISQPLA4	Strong	Biomarker	[21]
Inflammation	DISJUQ5T	Strong	Biomarker	[22]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[23]
leukaemia	DISS7D1V	Strong	Biomarker	[24]
Leukemia	DISNAKFL	Strong	Biomarker	[25]
Lymphoma	DISN6V4S	Strong	Biomarker	[8]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[26]
Mood disorder	DISLVMWO	Strong	Biomarker	[27]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[28]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[29]
Myelopathy	DISXV8FG	Strong	Biomarker	[30]
Neoplasm of testis	DISK4XHT	Strong	Genetic Variation	[31]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[32]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[33]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[12]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[12]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[34]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[35]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[36]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[36]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[37]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[38]

13 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 Activating transcription factor 7-interacting protein 1 (ATF7IP).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[41]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[42]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[45]
Marinol	DM70IK5	Approved	Marinol increases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[47]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[54]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[56]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[48]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[53]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[52]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Activating transcription factor 7-interacting protein 1 (ATF7IP).	[55]

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