Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTHH4YE)

• DOT Name: Immunoglobulin-binding protein 1 (IGBP1)
• Synonyms: B-cell signal transduction molecule alpha 4; Protein alpha-4; CD79a-binding protein 1; Protein phosphatase 2/4/6 regulatory subunit; Renal carcinoma antigen NY-REN-16
• Gene Name: IGBP1
• Related Disease:
  Adenocarcinoma
  Alport syndrome
  Cholangiocarcinoma
  Esophageal squamous cell carcinoma
  FG syndrome
  Hematuria, benign familial
  Lung adenocarcinoma
  Seasonal affective disorder
  X-linked Opitz G/BBB syndrome
  Lupus nephritis
  Nephritis
  Systemic lupus erythematosus
  Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome
  Autosomal dominant nocturnal frontal lobe epilepsy
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Hepatocellular carcinoma
  Lung cancer
  Lung neoplasm
• UniProt ID: IGBP1_HUMAN
• PDB ID: 4IYP
• Pfam ID: PF04177
• Sequence:
  MAAEDELQLPRLPELFETGRQLLDEVEVATEPAGSRIVQEKVFKGLDLLEKAAEMLSQLD
  LFSRNEDLEEIASTDLKYLLVPAFQGALTMKQVNPSKRLDHLQRAREHFINYLTQCHCYH
  VAEFELPKTMNNSAENHTANSSMAYPSLVAMASQRQAKIQRYKQKKELEHRLSAMKSAVE
  SGQADDERVREYYLLHLQRWIDISLEEIESIDQEIKILRERDSSREASTSNSSRQERPPV
  KPFILTRNMAQAKVFGAGYPSLPTMTVSDWYEQHRKYGALPDQGIAKAAPEEFRKAAQQQ
  EEQEEKEEEDDEQTLHRAREWDDWKDTHPRGYGNRQNMG
• Function: Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of the phosphatases PP2A, PP4 and PP6 by protecting their partially folded catalytic subunits from degradative polyubiquitination until they associate with regulatory subunits.
• Tissue Specificity: Ubiquitously expressed with highest levels in heart, skeletal muscle and pancreas.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Alport syndrome	DIS25AB4	Strong	Genetic Variation	[2]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[4]
FG syndrome	DIS2MEFU	Strong	Genetic Variation	[5]
Hematuria, benign familial	DISCWU1L	Strong	Genetic Variation	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Seasonal affective disorder	DIS908VO	Strong	Altered Expression	[6]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Altered Expression	[5]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[7]
Nephritis	DISQZQ70	moderate	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	moderate	Altered Expression	[7]
Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome	DIS52389	Supportive	X-linked	[8]
Autosomal dominant nocturnal frontal lobe epilepsy	DISE3C4O	Limited	Genetic Variation	[9]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[10]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[10]
Lung cancer	DISCM4YA	Limited	Biomarker	[10]
Lung neoplasm	DISVARNB	Limited	Biomarker	[10]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Microcystin-LR	DMTMLRN	Investigative	Immunoglobulin-binding protein 1 (IGBP1) increases the response to substance of Microcystin-LR.	[21]

7 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 Immunoglobulin-binding protein 1 (IGBP1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Immunoglobulin-binding protein 1 (IGBP1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Immunoglobulin-binding protein 1 (IGBP1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Immunoglobulin-binding protein 1 (IGBP1).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Immunoglobulin-binding protein 1 (IGBP1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Immunoglobulin-binding protein 1 (IGBP1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Immunoglobulin-binding protein 1 (IGBP1).	[19]

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 Immunoglobulin-binding protein 1 (IGBP1).	[17]

2 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 affects the methylation of Immunoglobulin-binding protein 1 (IGBP1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Immunoglobulin-binding protein 1 (IGBP1).	[20]

References

• [1] miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma.Cancer Sci. 2017 Mar;108(3):536-542. doi: 10.1111/cas.13148.
• [2] Alport syndrome and benign familial hematuria (thin basement membrane disease) in two brothers of a family with hematuria.Clin Nephrol. 2003 Sep;60(3):195-200. doi: 10.5414/cnp60195.
• [3] Aberrant DNA methylation of integrin alpha4: a potential novel role for metastasis of cholangiocarcinoma.J Cancer Res Clin Oncol. 2010 Feb;136(2):187-94. doi: 10.1007/s00432-009-0646-9. Epub 2009 Aug 5.
• [4] CpG island hypermethylation of E-cadherin (CDH1) and integrin alpha4 is associated with recurrence of early stage esophageal squamous cell carcinoma.Int J Cancer. 2008 Nov 1;123(9):2073-9. doi: 10.1002/ijc.23598.
• [5] Developmental expression of alpha4 protein phosphatase regulatory subunit in tissues affected by Opitz syndrome.Dev Dyn. 2002 Aug;224(4):461-4. doi: 10.1002/dvdy.10125.
• [6] Protein and mRNA levels of nicotinic receptors in brain of tobacco using controls and patients with Alzheimer's disease.Neuroscience. 2003;122(2):515-20. doi: 10.1016/s0306-4522(03)00460-3.
• [7] Immunoglobulin Binding Protein 1 as a Potential Urine Biomarker in Patients with Lupus Nephritis.Int J Mol Sci. 2019 May 27;20(10):2606. doi: 10.3390/ijms20102606.
• [8] A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. Am J Med Genet A. 2003 Nov 15;123A(1):37-44. doi: 10.1002/ajmg.a.20504.
• [9] Nicotine normalizes intracellular subunit stoichiometry of nicotinic receptors carrying mutations linked to autosomal dominant nocturnal frontal lobe epilepsy.Mol Pharmacol. 2009 May;75(5):1137-48. doi: 10.1124/mol.108.054494. Epub 2009 Feb 23.
• [10] 4 is highly expressed in carcinogen-transformed human cells and primary human cancers.Oncogene. 2011 Jun 30;30(26):2943-53. doi: 10.1038/onc.2011.20. Epub 2011 Feb 21.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [13] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [18] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Alpha4-overexpressing HL7702 cells can counteract microcystin-LR effects on cytoskeletal structure. Environ Toxicol. 2018 Sep;33(9):978-987. doi: 10.1002/tox.22585. Epub 2018 Jul 9.