Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUYL1TQ)

• DOT Name: General transcription factor II-I (GTF2I)
• Synonyms: GTFII-I; TFII-I; Bruton tyrosine kinase-associated protein 135; BAP-135; BTK-associated protein 135; SRF-Phox1-interacting protein; SPIN; Williams-Beuren syndrome chromosomal region 6 protein
• Gene Name: GTF2I
• Related Disease:
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Acute myelogenous leukaemia
  Anti-neutrophil cytoplasmic antibody-associated vasculitis
  Anxiety
  Anxiety disorder
  Atrial fibrillation
  Autism spectrum disorder
  Beckwith-Wiedemann syndrome
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Depression
  Epithelial neoplasm
  Malignant thymoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Promyelocytic leukaemia
  Rheumatoid arthritis
  Scleroderma
  Seasonal affective disorder
  Sjogren syndrome
  Stroke
  Thrombocytopenia
  Thymic epithelial neoplasm
  Differentiated thyroid carcinoma
  Lupus nephritis
  Systemic lupus erythematosus
  Cognitive impairment
  Angioimmunoblastic T-cell Lymphoma
  Autism
  Chronic obstructive pulmonary disease
  Familial atrial fibrillation
  Intellectual disability
  Neuromyelitis optica
  Sickle-cell anaemia
  Systemic sclerosis
• UniProt ID: GTF2I_HUMAN
• PDB ID: 2D9B; 2DN4; 2ED2; 2EJE
• Pfam ID: PF02946
• Sequence:
  MAQVAMSTLPVEDEESSESRMVVTFLMSALESMCKELAKSKAEVACIAVYETDVFVVGTE
  RGRAFVNTRKDFQKDFVKYCVEEEEKAAEMHKMKSTTQANRMSVDAVEIETLRKTVEDYF
  CFCYGKALGKSTVVPVPYEKMLRDQSAVVVQGLPEGVAFKHPENYDLATLKWILENKAGI
  SFIIKRPFLEPKKHVGGRVMVTDADRSILSPGGSCGPIKVKTEPTEDSGISLEMAAVTVK
  EESEDPDYYQYNIQAGPSETDDVDEKQPLSKPLQGSHHSSEGNEGTEMEVPAEDSTQHVP
  SETSEDPEVEVTIEDDDYSPPSKRPKANELPQPPVPEPANAGKRKVREFNFEKWNARITD
  LRKQVEELFERKYAQAIKAKGPVTIPYPLFQSHVEDLYVEGLPEGIPFRRPSTYGIPRLE
  RILLAKERIRFVIKKHELLNSTREDLQLDKPASGVKEEWYARITKLRKMVDQLFCKKFAE
  ALGSTEAKAVPYQKFEAHPNDLYVEGLPENIPFRSPSWYGIPRLEKIIQVGNRIKFVIKR
  PELLTHSTTEVTQPRTNTPVKEDWNVRITKLRKQVEEIFNLKFAQALGLTEAVKVPYPVF
  ESNPEFLYVEGLPEGIPFRSPTWFGIPRLERIVRGSNKIKFVVKKPELVISYLPPGMASK
  INTKALQSPKRPRSPGSNSKVPEIEVTVEGPNNNNPQTSAVRTPTQTNGSNVPFKPRGRE
  FSFEAWNAKITDLKQKVENLFNEKCGEALGLKQAVKVPFALFESFPEDFYVEGLPEGVPF
  RRPSTFGIPRLEKILRNKAKIKFIIKKPEMFETAIKESTSSKSPPRKINSSPNVNTTASG
  VEDLNIIQVTIPDDDNERLSKVEKARQLREQVNDLFSRKFGEAIGMGFPVKVPYRKITIN
  PGCVVVDGMPPGVSFKAPSYLEISSMRRILDSAEFIKFTVIRPFPGLVINNQLVDQSESE
  GPVIQESAEPSQLEVPATEEIKETDGSSQIKQEPDPTW
• Function: Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation.
• Tissue Specificity: Ubiquitous. Isoform 1 is strongly expressed in fetal brain, weakly in adult brain, muscle, and lymphoblasts and is almost undetectable in other adult tissues, while the other isoforms are equally expressed in all adult tissues.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  cGMP-PKG sig.ling pathway (hsa04022)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peeling skin syndrome 1	DIS35574	Definitive	Genetic Variation	[1]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Anti-neutrophil cytoplasmic antibody-associated vasculitis	DISBEQIT	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[4]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[5]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Epithelial neoplasm	DIS0T594	Strong	Genetic Variation	[11]
Malignant thymoma	DIS59MOU	Strong	Genetic Variation	[12]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[13]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[14]
Promyelocytic leukaemia	DISYGG13	Strong	Genetic Variation	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[16]
Scleroderma	DISVQ342	Strong	Genetic Variation	[17]
Seasonal affective disorder	DIS908VO	Strong	Biomarker	[18]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[1]
Stroke	DISX6UHX	Strong	Biomarker	[19]
Thrombocytopenia	DISU61YW	Strong	Genetic Variation	[20]
Thymic epithelial neoplasm	DISWIT0F	Strong	Biomarker	[21]
Differentiated thyroid carcinoma	DIS1V20Y	moderate	Biomarker	[13]
Lupus nephritis	DISCVGPZ	moderate	Genetic Variation	[22]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[14]
Cognitive impairment	DISH2ERD	Disputed	Biomarker	[23]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Limited	Genetic Variation	[24]
Autism	DISV4V1Z	Limited	Genetic Variation	[25]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[26]
Familial atrial fibrillation	DISL4AGF	Limited	Biomarker	[5]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[27]
Neuromyelitis optica	DISBFGKL	Limited	Genetic Variation	[16]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[19]
Systemic sclerosis	DISF44L6	Limited	Genetic Variation	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	General transcription factor II-I (GTF2I) affects the response to substance of Topotecan.	[47]
Vinblastine	DM5TVS3	Approved	General transcription factor II-I (GTF2I) affects the response to substance of Vinblastine.	[47]

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 General transcription factor II-I (GTF2I).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of General transcription factor II-I (GTF2I).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of General transcription factor II-I (GTF2I).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of General transcription factor II-I (GTF2I).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of General transcription factor II-I (GTF2I).	[33]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of General transcription factor II-I (GTF2I).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of General transcription factor II-I (GTF2I).	[35]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of General transcription factor II-I (GTF2I).	[36]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of General transcription factor II-I (GTF2I).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of General transcription factor II-I (GTF2I).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of General transcription factor II-I (GTF2I).	[43]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of General transcription factor II-I (GTF2I).	[44]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of General transcription factor II-I (GTF2I).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the phosphorylation of General transcription factor II-I (GTF2I).	[31]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of General transcription factor II-I (GTF2I).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of General transcription factor II-I (GTF2I).	[39]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of General transcription factor II-I (GTF2I).	[40]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of General transcription factor II-I (GTF2I).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of General transcription factor II-I (GTF2I).	[41]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of General transcription factor II-I (GTF2I).	[45]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of General transcription factor II-I (GTF2I).	[38]

References

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