Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVYQ7ZL)

• DOT Name: Ankyrin repeat and KH domain-containing protein 1 (ANKHD1)
• Synonyms: HIV-1 Vpr-binding ankyrin repeat protein; Multiple ankyrin repeats single KH domain; hMASK
• Gene Name: ANKHD1
• Related Disease:
  Acute leukaemia
  Advanced cancer
  Allergic rhinitis
  Clear cell renal carcinoma
  Hepatocellular carcinoma
  Leukemia
  Metastatic malignant neoplasm
  Neoplasm
  Renal cell carcinoma
  Rhinitis
  Breast cancer
  Breast carcinoma
  Parkinson disease
  Plasma cell myeloma
• UniProt ID: ANKH1_HUMAN
• Pfam ID: PF12796 ; PF13637 ; PF00013
• Sequence:
  MLTDSGGGGTSFEEDLDSVAPRSAPAGASEPPPPGGVGLGIRTVRLFGEAGPASGVGSSG
  GGGSGSGTGGGDAALDFKLAAAVLRTGGGGGASGSDEDEVSEVESFILDQEDLDNPVLKT
  TSEIFLSSTAEGADLRTVDPETQARLEALLEAAGIGKLSTADGKAFADPEVLRRLTSSVS
  CALDEAAAALTRMKAENSHNAGQVDTRSLAEACSDGDVNAVRKLLDEGRSVNEHTEEGES
  LLCLACSAGYYELAQVLLAMHANVEDRGNKGDITPLMAASSGGYLDIVKLLLLHDADVNS
  QSATGNTALTYACAGGFVDIVKVLLNEGANIEDHNENGHTPLMEAASAGHVEVARVLLDH
  GAGINTHSNEFKESALTLACYKGHLDMVRFLLEAGADQEHKTDEMHTALMEACMDGHVEV
  ARLLLDSGAQVNMPADSFESPLTLAACGGHVELAALLIERGANLEEVNDEGYTPLMEAAR
  EGHEEMVALLLAQGANINAQTEETQETALTLACCGGFSEVADFLIKAGADIELGCSTPLM
  EASQEGHLELVKYLLASGANVHATTATGDTALTYACENGHTDVADVLLQAGADLEHESEG
  GRTPLMKAARAGHLCTVQFLISKGANVNRATANNDHTVVSLACAGGHLAVVELLLAHGAD
  PTHRLKDGSTMLIEAAKGGHTNVVSYLLDYPNNVLSVPTTDVSQLPPPSQDQSQVPRVPT
  HTLAMVVPPQEPDRTSQENSPALLGVQKGTSKQKSSSLQVADQDLLPSFHPYQPLECIVE
  ETEGKLNELGQRISAIEKAQLKSLELIQGEPLNKDKIEELKKNREEQVQKKKKILKELQK
  VERQLQMKTQQQFTKEYLETKGQKDTVSLHQQCSHRGVFPEGEGDGSLPEDHFSELPQVD
  TILFKDNDVDDEQQSPPSAEQIDFVPVQPLSSPQCNFSSDLGSNGTNSLELQKVSGNQQI
  VGQPQIAITGHDQGLLVQEPDGLMVATPAQTLTDTLDDLIAAVSTRVPTGSNSSSQTTEC
  LTPESCSQTTSNVASQSMPPVYPSVDIDAHTESNHDTALTLACAGGHEELVSVLIARDAK
  IEHRDKKGFTPLILAATAGHVGVVEILLDKGGDIEAQSERTKDTPLSLACSGGRQEVVDL
  LLARGANKEHRNVSDYTPLSLAASGGYVNIIKILLNAGAEINSRTGSKLGISPLMLAAMN
  GHVPAVKLLLDMGSDINAQIETNRNTALTLACFQGRAEVVSLLLDRKANVEHRAKTGLTP
  LMEAASGGYAEVGRVLLDKGADVNAPPVPSSRDTALTIAADKGHYKFCELLIHRGAHIDV
  RNKKGNTPLWLASNGGHFDVVQLLVQAGADVDAADNRKITPLMSAFRKGHVKVVQYLVKE
  VNQFPSDIECMRYIATITDKELLKKCHQCVETIVKAKDQQAAEANKNASILLKELDLEKS
  REESRKQALAAKREKRKEKRKKKKEEQKRKQEEDEENKPKENSELPEDEDEEENDEDVEQ
  EVPIEPPSATTTTTIGISATSATFTNVFGKKRANVVTTPSTNRKNKKNKTKETPPTAHLI
  LPEQHMSLAQQKADKNKINGEPRGGGAGGNSDSDNLDSTDCNSESSSGGKSQELNFVMDV
  NSSKYPSLLLHSQEEKTSTATSKTQTRLEGEVTPNSLSTSYKTVSLPLSSPNIKLNLTSP
  KRGQKREEGWKEVVRRSKKLSVPASVVSRIMGRGGCNITAIQDVTGAHIDVDKQKDKNGE
  RMITIRGGTESTRYAVQLINALIQDPAKELEDLIPKNHIRTPASTKSIHANFSSGVGTTA
  ASSKNAFPLGAPTLVTSQATTLSTFQPANKLNKNVPTNVRSSFPVSLPLAYPHPHFALLA
  AQTMQQIRHPRLPMAQFGGTFSPSPNTWGPFPVRPVNPGNTNSSPKHNNTSRLPNQNGTV
  LPSESAGLATASCPITVSSVVAASQQLCVTNTRTPSSVRKQLFACVPKTSPPATVISSVT
  STCSSLPSVSSAPITSGQAPTTFLPASTSQAQLSSQKMESFSAVPPTKEKVSTQDQPMAN
  LCTPSSTANSCSSSASNTPGAPETHPSSSPTPTSSNTQEEAQPSSVSDLSPMSMPFASNS
  EPAPLTLTSPRMVAADNQDTSNLPQLAVPAPRVSHRMQPRGSFYSMVPNATIHQDPQSIF
  VTNPVTLTPPQGPPAAVQLSSAVNIMNGSQMHINPANKSLPPTFGPATLFNHFSSLFDSS
  QVPANQGWGDGPLSSRVATDASFTVQSAFLGNSVLGHLENMHPDNSKAPGFRPPSQRVST
  SPVGLPSIDPSGSSPSSSSAPLASFSGIPGTRVFLQGPAPVGTPSFNRQHFSPHPWTSAS
  NSSTSAPPTLGQPKGVSASQDRKIPPPIGTERLARIRQGGSVAQAPAGTSFVAPVGHSGI
  WSFGVNAVSEGLSGWSQSVMGNHPMHQQLSDPSTFSQHQPMERDDSGMVAPSNIFHQPMA
  SGFVDFSKGLPISMYGGTIIPSHPQLADVPGGPLFNGLHNPDPAWNPMIKVIQNSTECTD
  AQQIWPGTWAPHIGNMHLKYVN
• Function: May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases.
• Tissue Specificity: Ubiquitous with high expression in cervix, spleen and brain. Expressed in hematopoietic cells with increased expression in leukemia cells. Isoform 2 is highly expressed in spleen with almost no expression in muscle and brain.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Leukemia	DISNAKFL	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[2]
Rhinitis	DISKLMN7	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[7]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[8]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[17]

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 decreases the phosphorylation of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Ankyrin repeat and KH domain-containing protein 1 (ANKHD1).	[19]

References

• [1] ANKHD1 regulates cell cycle progression and proliferation in multiple myeloma cells.FEBS Lett. 2012 Dec 14;586(24):4311-8. doi: 10.1016/j.febslet.2012.10.037. Epub 2012 Nov 6.
• [2] Ankyrin repeat and single KH domain 1 (ANKHD1) drives renal cancer cell proliferation via binding to and altering a subset of miRNAs.J Biol Chem. 2018 Jun 22;293(25):9570-9579. doi: 10.1074/jbc.RA117.000975. Epub 2018 Apr 25.
• [3] Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.J Allergy Clin Immunol. 2019 Jul;144(1):135-143.e6. doi: 10.1016/j.jaci.2019.01.053. Epub 2019 Apr 3.
• [4] ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma.J Exp Clin Cancer Res. 2019 Jan 15;38(1):18. doi: 10.1186/s13046-018-1011-0.
• [5] ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute leukemias and is associated with SHP2 in K562 cells.Biochim Biophys Acta. 2006 Sep;1762(9):828-34. doi: 10.1016/j.bbadis.2006.07.010. Epub 2006 Jul 31.
• [6] Interactions Between Air Pollution and Pollen Season for Rhinitis Using Mobile Technology: A MASK-POLLAR Study.J Allergy Clin Immunol Pract. 2020 Mar;8(3):1063-1073.e4. doi: 10.1016/j.jaip.2019.11.022. Epub 2019 Nov 28.
• [7] Mask is required for the activity of the Hippo pathway effector Yki/YAP.Curr Biol. 2013 Feb 4;23(3):229-35. doi: 10.1016/j.cub.2012.12.033. Epub 2013 Jan 17.
• [8] Mask loss-of-function rescues mitochondrial impairment and muscle degeneration of Drosophila pink1 and parkin mutants.Hum Mol Genet. 2015 Jun 1;24(11):3272-85. doi: 10.1093/hmg/ddv081. Epub 2015 Mar 5.
• [9] ANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth.Eur J Cancer. 2015 Jan;51(2):252-9. doi: 10.1016/j.ejca.2014.11.012. Epub 2014 Dec 4.
• [10] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [11] 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.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] 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.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.