Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7XPG27)

• DOT Name: A-kinase-interacting protein 1 (AKIP1)
• Synonyms: Breast cancer-associated gene 3 protein; PKA-interacting protein; Proline-rich protein BCA3
• Gene Name: AKIP1
• Related Disease:
  Esophageal squamous cell carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast fibrocystic disease
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Esophageal cancer
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Stomach cancer
  Non-small-cell lung cancer
• UniProt ID: AKIP1_HUMAN
• Sequence:
  MDNCLAAAALNGVDRRSLQRSARLALEVLERAKRRAVDWHALERPKGCMGVLAREAPHLE
  KQPAAGPQRVLPGEREERPPTLSASFRTMAEFMDYTSSQCGKYYSSVPEEGGATHVYRYH
  RGESKLHMCLDIGNGQRKDRKKTSLGPGGSYQISEHAPEASQPAENISKDLYIEVYPGTY
  SVTVGSNDLTKKTHVVAVDSGQSVDLVFPV
• Function: Enhances NF-kappa-B transcriptional activity by regulating the nuclear localization of the NF-kappa-B subunit RELA and promoting the phosphorylation of RELA by PRKACA. Regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade.
• Tissue Specificity: Expressed at high levels in adult heart and at lower levels in brain, testis, ovary and skeletal muscle. Up-regulated in some breast cancer cell lines. Isoform 1 and isoform 3 are expressed in fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast fibrocystic disease	DISUM7ID	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Altered Expression	[11]

12 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 A-kinase-interacting protein 1 (AKIP1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of A-kinase-interacting protein 1 (AKIP1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of A-kinase-interacting protein 1 (AKIP1).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of A-kinase-interacting protein 1 (AKIP1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of A-kinase-interacting protein 1 (AKIP1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of A-kinase-interacting protein 1 (AKIP1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of A-kinase-interacting protein 1 (AKIP1).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of A-kinase-interacting protein 1 (AKIP1).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of A-kinase-interacting protein 1 (AKIP1).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of A-kinase-interacting protein 1 (AKIP1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of A-kinase-interacting protein 1 (AKIP1).	[12]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of A-kinase-interacting protein 1 (AKIP1).	[23]

1 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 decreases the methylation of A-kinase-interacting protein 1 (AKIP1).	[21]

References

• [1] Overexpression of AKIP1 promotes angiogenesis and lymphangiogenesis in human esophageal squamous cell carcinoma.Oncogene. 2015 Jan 15;34(3):384-93. doi: 10.1038/onc.2013.559. Epub 2014 Jan 13.
• [2] A-kinase interacting protein 1 might serve as a novel biomarker for worse prognosis through the interaction of chemokine (C-X-C motif) ligand 1/chemokine (C-X-C motif) ligand 2 in acute myeloid leukemia.J Clin Lab Anal. 2020 Feb;34(2):e23052. doi: 10.1002/jcla.23052. Epub 2019 Oct 16.
• [3] Upregulation of AKIP1 contributes to metastasis and progression and predicts poor prognosis of patients with colorectal cancer.Onco Targets Ther. 2018 Oct 11;11:6795-6801. doi: 10.2147/OTT.S151952. eCollection 2018.
• [4] Breast cancer-associated gene 3 interacts with Rac1 and augments NF-B signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo.Int J Mol Med. 2017 Oct;40(4):1067-1077. doi: 10.3892/ijmm.2017.3091. Epub 2017 Aug 4.
• [5] Does BCA3 Play a Role in the HIV-1 Replication Cycle?.Viruses. 2018 Apr 20;10(4):212. doi: 10.3390/v10040212.
• [6] Peripheral blood lymphocytes from patients with cancer lack interleukin-2 receptors.Cancer. 1988 Feb 15;61(4):689-701. doi: 10.1002/1097-0142(19880215)61:4<689::aid-cncr2820610412>3.0.co;2-o.
• [7] Characterization of a novel human breast cancer associated gene (BCA3) encoding an alternatively spliced proline-rich protein.Biochim Biophys Acta. 2003 Jan 3;1625(1):116-21. doi: 10.1016/s0167-4781(02)00562-6.
• [8] AKIP1 promotes angiogenesis and tumor growth by upregulating CXC-chemokines in cervical cancer cells.Mol Cell Biochem. 2018 Nov;448(1-2):311-320. doi: 10.1007/s11010-018-3335-7. Epub 2018 Mar 8.
• [9] A-kinase-interacting protein 1 facilitates growth and metastasis of gastric cancer cells via Slug-induced epithelial-mesenchymal transition.J Cell Mol Med. 2019 Jun;23(6):4434-4442. doi: 10.1111/jcmm.14339. Epub 2019 Apr 24.
• [10] AKIP1 promotes early recurrence of hepatocellular carcinoma through activating the Wnt/-catenin/CBP signaling pathway.Oncogene. 2019 Jul;38(27):5516-5529. doi: 10.1038/s41388-019-0807-5. Epub 2019 Apr 1.
• [11] A-kinase-interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles, and promotes cell proliferation but represses apoptosis in non-small-cell lung cancer.J Clin Lab Anal. 2020 Feb;34(2):e23061. doi: 10.1002/jcla.23061. Epub 2019 Dec 11.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] 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.
• [15] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [19] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [20] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [21] 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.
• [22] 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.
• [23] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.