Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGKB7Y2)

• DOT Name: Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1)
• Synonyms: EC 2.3.2.31
• Gene Name: ANKIB1
• Related Disease:
  Bone osteosarcoma
  Breast carcinoma
  Osteosarcoma
• UniProt ID: AKIB1_HUMAN
• EC Number: 2.3.2.31
• Pfam ID: PF00023 ; PF12796 ; PF19422 ; PF01485
• Sequence:
  MGNTTTKFRKALINGDENLACQIYENNPQLKESLDPNTSYGEPYQHNTPLHYAARHGMNK
  ILGTFLGRDGNPNKRNVHNETSMHLLCMGPQIMISEGALHPRLARPTEDDFRRADCLQMI
  LKWKGAKLDQGEYERAAIDAVDNKKNTPLHYAAASGMKACVELLVKHGGDLFAENENKDT
  PCDCAEKQHHKDLALNLESQMVFSRDPEAEEIEAEYAALDKREPYEGLRPQDLRRLKDML
  IVETADMLQAPLFTAEALLRAHDWDREKLLEAWMSNPENCCQRSGVQMPTPPPSGYNAWD
  TLPSPRTPRTTRSSVTSPDEISLSPGDLDTSLCDICMCSISVFEDPVDMPCGHDFCRGCW
  ESFLNLKIQEGEAHNIFCPAYDCFQLVPVDIIESVVSKEMDKRYLQFDIKAFVENNPAIK
  WCPTPGCDRAVRLTKQGSNTSGSDTLSFPLLRAPAVDCGKGHLFCWECLGEAHEPCDCQT
  WKNWLQKITEMKPEELVGVSEAYEDAANCLWLLTNSKPCANCKSPIQKNEGCNHMQCAKC
  KYDFCWICLEEWKKHSSSTGGYYRCTRYEVIQHVEEQSKEMTVEAEKKHKRFQELDRFMH
  YYTRFKNHEHSYQLEQRLLKTAKEKMEQLSRALKETEGGCPDTTFIEDAVHVLLKTRRIL
  KCSYPYGFFLEPKSTKKEIFELMQTDLEMVTEDLAQKVNRPYLRTPRHKIIKAACLVQQK
  RQEFLASVARGVAPADSPEAPRRSFAGGTWDWEYLGFASPEEYAEFQYRRRHRQRRRGDV
  HSLLSNPPDPDEPSESTLDIPEGGSSSRRPGTSVVSSASMSVLHSSSLRDYTPASRSENQ
  DSLQALSSLDEDDPNILLAIQLSLQESGLALDEETRDFLSNEASLGAIGTSLPSRLDSVP
  RNTDSPRAALSSSELLELGDSLMRLGAENDPFSTDTLSSHPLSEARSDFCPSSSDPDSAG
  QDPNINDNLLGNIMAWFHDMNPQSIALIPPATTEISADSQLPCIKDGSEGVKDVELVLPE
  DSMFEDASVSEGRGTQIEENPLEENILAGEAASQAGDSGNEAANRGDGSDVSSQTPQTSS
  DWLEQVHLV
• Function: Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[10]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1).	[12]

References

• [1] Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion.Hum Cell. 2020 Jan;33(1):252-260. doi: 10.1007/s13577-019-00298-6. Epub 2019 Oct 30.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.