Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT887N3O)

• DOT Name: Importin-13 (IPO13)
• Synonyms: Imp13; Karyopherin-13; Kap13; Ran-binding protein 13; RanBP13
• Gene Name: IPO13
• Related Disease:
  Advanced cancer
  Breast cancer
  Bronchopulmonary dysplasia
  Endometrial carcinoma
  Endometriosis
  Gastric cancer
  Stomach cancer
  Asthma
  Cataract
  Coloboma
  Microphthalmia
• UniProt ID: IPO13_HUMAN
• PDB ID: 2X19; 2XWU; 3ZJY
• Pfam ID: PF03810 ; PF18773 ; PF18786 ; PF18806 ; PF08389
• Sequence:
  MERREEQPGAAGAGAAPALDFTVENVEKALHQLYYDPNIENKNLAQKWLMQAQVSPQAWH
  FSWQLLQPDKVPEIQYFGASALHIKISRYWSDIPTDQYESLKAQLFTQITRFASGSKIVL
  TRLCVALASLALSMMPDAWPCAVADMVRLFQAEDSPVDGQGRCLALLELLTVLPEEFQTS
  RLPQYRKGLVRTSLAVECGAVFPLLEQLLQQPSSPSCVRQKVLKCFSSWVQLEVPLQDCE
  ALIQAAFAALQDSELFDSSVEAIVNAISQPDAQRYVNTLLKLIPLVLGLQEQLRQAVQNG
  DMETSHGICRIAVALGENHSRALLDQVEHWQSFLALVNMIMFCTGIPGHYPVNETTSSLT
  LTFWYTLQDDILSFEAEKQAVYQQVYRPVYFQLVDVLLHKAQFPSDEEYGFWSSDEKEQF
  RIYRVDISDTLMYVYEMLGAELLSNLYDKLGRLLTSSEEPYSWQHTEALLYGFQSIAETI
  DVNYSDVVPGLIGLIPRISISNVQLADTVMFTIGALSEWLADHPVMINSVLPLVLHALGN
  PELSVSSVSTLKKICRECKYDLPPYAANIVAVSQDVLMKQIHKTSQCMWLMQALGFLLSA
  LQVEEILKNLHSLISPYIQQLEKLAEEIPNPSNKLAIVHILGLLSNLFTTLDISHHEDDH
  EGPELRKLPVPQGPNPVVVVLQQVFQLIQKVLSKWLNDAQVVEAVCAIFEKSVKTLLDDF
  APMVPQLCEMLGRMYSTIPQASALDLTRQLVHIFAHEPAHFPPIEALFLLVTSVTLTLFQ
  QGPRDHPDIVDSFMQLLAQALKRKPDLFLCERLDVKAVFQCAVLALKFPEAPTVKASCGF
  FTELLPRCGEVESVGKVVQEDGRMLLIAVLEAIGGQASRSLMDCFADILFALNKHCFSLL
  SMWIKEALQPPGFPSARLSPEQKDTFSQQILRERVNKRRVKEMVKEFTLLCRGLHGTDYT
  ADY
• Function: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.
• Tissue Specificity: Expressed in fetal brain, heart, intestine and kidney.
• KEGG Pathway: Nucleocytoplasmic transport (hsa03013)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Genetic Variation	[3]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[4]
Endometriosis	DISX1AG8	Strong	Altered Expression	[4]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[5]
Asthma	DISW9QNS	Limited	Biomarker	[6]
Cataract	DISUD7SL	Limited	Genetic Variation	[7]
Coloboma	DISP39N5	Limited	Biomarker	[7]
Microphthalmia	DISGEBES	Limited	Biomarker	[7]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Importin-13 (IPO13).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Importin-13 (IPO13).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Importin-13 (IPO13).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Importin-13 (IPO13).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Importin-13 (IPO13).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Importin-13 (IPO13).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Importin-13 (IPO13).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Importin-13 (IPO13).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Importin-13 (IPO13).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Importin-13 (IPO13).	[15]

References

• [1] Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis.Oncogene. 2012 Apr 19;31(16):2062-74. doi: 10.1038/onc.2011.383. Epub 2011 Aug 29.
• [2] The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer.Cancer Res. 2008 Jan 15;68(2):537-44. doi: 10.1158/0008-5472.CAN-07-5682.
• [3] The impact of glucocorticoid polymorphisms on markers of neonatal respiratory disease after antenatal betamethasone administration.Am J Obstet Gynecol. 2013 Mar;208(3):215.e1-6. doi: 10.1016/j.ajog.2012.12.031. Epub 2013 Jan 4.
• [4] Increased expression of importin13 in endometriosis and endometrial carcinoma.Med Sci Monit. 2012 Jun;18(6):CR361-7. doi: 10.12659/msm.882879.
• [5] Deregulation of the cell polarity protein Lethal giant larvae 2 (Lgl2) correlates with gastric cancer progression.Gastric Cancer. 2014 Oct;17(4):610-20. doi: 10.1007/s10120-013-0324-0. Epub 2013 Dec 13.
• [6] Importin-13 genetic variation is associated with improved airway responsiveness in childhood asthma.Respir Res. 2009 Jul 20;10(1):67. doi: 10.1186/1465-9921-10-67.
• [7] Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract.Exp Mol Med. 2018 Apr 27;50(4):1-11. doi: 10.1038/s12276-018-0079-0.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] DNA microarray analysis of changes in gene expression induced by 1,25-dihydroxyvitamin D3 in human promyelocytic leukemia HL-60 cells. Biomed Res. 2006 Jun;27(3):99-109. doi: 10.2220/biomedres.27.99.
• [12] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.