Details of Drug Off-Target (DOT)

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

• DOT Name: Pre-B-cell leukemia transcription factor 1 (PBX1)
• Synonyms: Homeobox protein PBX1; Homeobox protein PRL
• Gene Name: PBX1
• Related Disease:
  Acute myelogenous leukaemia
  Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
  Metabolic disorder
  Acute leukaemia
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Carcinoma of esophagus
  Congenital anomaly of kidney and urinary tract
  Drug dependence
  Epithelial ovarian cancer
  Esophageal cancer
  Haematological malignancy
  Intellectual disability
  Lupus
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obsessive compulsive disorder
  Ovarian cancer
  Ovarian neoplasm
  Promyelocytic leukaemia
  Prostate neoplasm
  Squamous cell carcinoma
  Substance abuse
  Substance dependence
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Anxiety
  Anxiety disorder
  Lymphoid leukemia
  Melanoma
  Small lymphocytic lymphoma
  Stomach cancer
  Advanced cancer
  B-cell acute lymphoblastic leukaemia
  Chromosomal disorder
  Fetal growth restriction
  Glaucoma/ocular hypertension
  leukaemia
  Lymphoma
  Myeloid leukaemia
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PBX1_HUMAN
• PDB ID: 1B72; 1PUF
• Pfam ID: PF05920 ; PF03792
• Sequence:
  MDEQPRLMHSHAGVGMAGHPGLSQHLQDGAGGTEGEGGRKQDIGDILQQIMTITDQSLDE
  AQARKHALNCHRMKPALFNVLCEIKEKTVLSIRGAQEEEPTDPQLMRLDNMLLAEGVAGP
  EKGGGSAAAAAAAAASGGAGSDNSVEHSDYRAKLSQIRQIYHTELEKYEQACNEFTTHVM
  NLLREQSRTRPISPKEIERMVSIIHRKFSSIQMQLKQSTCEAVMILRSRFLDARRKRRNF
  NKQATEILNEYFYSHLSNPYPSEEAKEELAKKCGITVSQVSNWFGNKRIRYKKNIGKFQE
  EANIYAAKTAVTATNVSAHGSQANSPSTPNSAGSSSSFNMSNSGDLFMSVQSLNGDSYQG
  AQVGANVQSQVDTLRHVISQTGGYSDGLAASQMYSPQGISANGGWQDATTPSSVTSPTEG
  PGSVHSDTSN
• Function: Transcription factor which binds the DNA sequence 5'-TGATTGAT-3' as part of a heterodimer with HOX proteins such as HOXA1, HOXA5, HOXB7 and HOXB8. Binds to the DNA sequence 5'-TGATTGAC-3' in complex with a nuclear factor which is not a class I HOX protein. Has also been shown to bind the DNA sequence 5'-ATCAATCAA-3' cooperatively with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4. Acts as a transcriptional activator of PF4 in complex with MEIS1. Also activates transcription of SOX3 in complex with MEIS1 by binding to the 5'-TGATTGAC-3' consensus sequence. In natural killer cells, binds to the NFIL3 promoter and acts as a transcriptional activator of NFIL3, promoting natural killer cell development. Plays a role in the cAMP-dependent regulation of CYP17A1 gene expression via its cAMP-regulatory sequence (CRS1). Probably in complex with MEIS2, involved in transcriptional regulation by KLF4. Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B. Together with NKX2-5, required for spleen development through a mechanism that involves CDKN2B repression; [Isoform PBX1b]: As part of a PDX1:PBX1b:MEIS2B complex in pancreatic acinar cells, is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element.
• Tissue Specificity: Expressed in the kidney. Expressed in the endothelial cells of the glomeruli and interstitium (at protein level) . Expressed in all tissues except in cells of the B and T lineage. Expressed strongly in kidney and brain .
• KEGG Pathway:
  Efferocytosis (hsa04148)
  Cortisol synthesis and secretion (hsa04927)
  Cushing syndrome (hsa04934)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	DISTB378	Definitive	Autosomal dominant	[2]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[3]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Congenital anomaly of kidney and urinary tract	DIS84IVH	Strong	Biomarker	[9]
Drug dependence	DIS9IXRC	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[12]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[13]
Lupus	DISOKJWA	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[16]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[19]
Substance abuse	DIS327VW	Strong	Biomarker	[10]
Substance dependence	DISDRAAR	Strong	Biomarker	[10]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[14]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[20]
Anxiety	DISIJDBA	moderate	Altered Expression	[21]
Anxiety disorder	DISBI2BT	moderate	Altered Expression	[21]
Lymphoid leukemia	DIS65TYQ	moderate	Biomarker	[22]
Melanoma	DIS1RRCY	moderate	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[24]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[25]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[26]
B-cell acute lymphoblastic leukaemia	DISKLOKC	Limited	Genetic Variation	[27]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[28]
Fetal growth restriction	DIS5WEJ5	Limited	Genetic Variation	[9]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[29]
leukaemia	DISS7D1V	Limited	Altered Expression	[30]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[31]
Myeloid leukaemia	DISMN944	Limited	Biomarker	[32]
Prostate cancer	DISF190Y	Limited	Biomarker	[33]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Pre-B-cell leukemia transcription factor 1 (PBX1) affects the response to substance of Cisplatin.	[51]
Mitoxantrone	DMM39BF	Approved	Pre-B-cell leukemia transcription factor 1 (PBX1) affects the response to substance of Mitoxantrone.	[51]

16 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 Pre-B-cell leukemia transcription factor 1 (PBX1).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[40]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[41]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[43]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[44]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[49]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Pre-B-cell leukemia transcription factor 1 (PBX1).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Pre-B-cell leukemia transcription factor 1 (PBX1).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pre-B-cell leukemia transcription factor 1 (PBX1).	[48]

References

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