Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBDW2F2)

• DOT Name: Ankyrin repeat domain-containing protein 31 (ANKRD31)
• Gene Name: ANKRD31
• Related Disease: Alzheimer disease
• UniProt ID: ANR31_HUMAN
• Pfam ID: PF12796 ; PF18755
• Sequence:
  MEEGVQAPDWDSDETVIEGSVTESDLEEKELPWRRLLFDQDASLKSEFSLHPDTRGMCKG
  MPSPEIQLGFKLREDLQEQMNKNKMMPVLSEDTILQSQDETERNQALLQTRKNCSMFIGS
  FRQSGLSLNHQNIEGPEAESPEVLPHIEKELSEGRDSPEVSLLSGTAITVSDTVAVKETS
  LVEPEKILAAPNTFFEPRKEVTMTMTSEETKDEESSLETFVSALESLLTSPESTQEERLF
  ELVSDFDRKELMNPLSDSLSSISIPLNSWSACHRDLLEDAKDDALPAELLEALNTLSEAK
  VETICHRKEGGSSLIARNECLEVEFNTSQTNEDCTQIAETLQDPNPSGLQTLAHQNITSC
  EPLSNKRNSNSVTNSSDQETACVLRRSSRLEKLKVSRDAKYSDHMYKMPEKILPKILGCE
  DLTNNNSSAQNFRMQDPALMIDGKEKNMHSARFKNGKQIRKNEQFSGKKEKMKVNKISLH
  SINRRNIFGENLVYKAALHDDADLVHHCIKKGGNVNQPSYAGWTALHEASVGGFYRTASE
  LLKGGADVNIKGLYQITPLHDAVMNGHYKVAELLLLNGADPLFRNDDGKCALDEAKDLCM
  KRLLERYIPKHQKCLTSAQRSSIDPLDIEDVYQHKKPKFSSKSHIWHVYNENSNRQKLEH
  VKVNKGSKASLFINKEDVYEYYQKDPKNTKFGKSKHKQSTLDQIYSTGLRKGNLHNVKDP
  NTNVPKGIGRRKTQHKRTQVDDVDCNPRKILAVSPSRRINRLVTYQQHIPETHNDLPEEL
  CEPSSLTLSSLRNGLDSSTEACSVSKEKHIQNLDLSDSQEVQCLELESVDQTEAVSFPGL
  LLHKEIKLPVVTTDKQPHTLQEQHHVLYKSHENSNLVPKDERFNKWENSFLSFVKENSDN
  DDDDDCSTSEKAITSKKVLCSTGGKKHYNFKENLTNKKEMGFQQFLLSEDHLSQENELKA
  VSLTTLPEQEAVNFSYSDNAVISEHVANYEQCIFGPSFDHSNGNPEQNSLACMRTLLTHE
  ASKLTNHVELFKKPQDYIPRAPTFLMNQTDTHIVEKMAKNCDTERNYIDRDQKIIYSNEP
  LSIVAHSQVIETTKVEKRRQNHLESETIHNIDSHSTDNMSKELANISKLSQREKKEISHK
  PGMKAGRINKRNARGESQLHLAVRRGNLPLVKALIESGADVNLNDNAGWTPLHEASNEGS
  IDIIVELLKAGAKVNCENIDGILPLHDAVANNHLKAAEILLQNGANPNQKDQKQKSALDE
  ADDEKMKELLRSYGAIETVNRDESDAIVNEKIPAVRSKRHKQCFCDDGKTIDSSSLSHQE
  RSRESLSVHQTLSAILQDIEEKQEYLLEFEIRNPEDAEQYIEKMLKIKKIMDNVLAKQKA
  ERDDLAKKYRVSIESFKHGALREQLANLAARQKSLLVVAKKQKKISLKIQNCRNVTSLPC
  LSLRKLPPRSEISSEKDSQELTSLENLEHPQSGSLSPVSGSMQETQLSLETWNYSQNTNI
  CLNSEAVRRGEFSGNDMNSKQNGSDCTLDGFPKSRHSDGTEKNKLPSQPVAFIGQTEYSQ
  KENDLTEATDKDHEFYVSSPVIGKLNISETASVLAENAAHPSNIICDQDLSNYDPKRGNR
  KTSSQQSPTGASESLAHQGIAVLGSDTVHQMKPYLKKSVSVVPCADDSQISSSSGSGQQD
  TIKKALNYSTAPKKKCIQIKDLILLGRINPGNNILEFKTQETTHKASILLNGKLKVESGQ
  IYKNPVTWLKDLLGGNSYVTWNYAWSKVTYLGKELLRYVSEDAPILPEPNSVPQQYQPCL
  PEVACLDDPVQEPNKSMFEKTKFGQGTSRESMQSSPRYLQINEILLISDQEFLPCHIMDQ
  HWKFCVECEELTP
• Function: Required for DNA double-strand breaks (DSBs) formation during meiotic recombination. Regulates the spatial and temporal patterns of pre-DSB recombinosome assembly and recombination activity by acting as a scaffold that anchors REC114 and other factors to specific genomic locations, thereby regulating DSB formation. Plays a key role in recombination in the pseudoautosomal regions of sex chromosomes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Ankyrin repeat domain-containing protein 31 (ANKRD31).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ankyrin repeat domain-containing protein 31 (ANKRD31).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Ankyrin repeat domain-containing protein 31 (ANKRD31).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin repeat domain-containing protein 31 (ANKRD31).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ankyrin repeat domain-containing protein 31 (ANKRD31).	[6]

References

• [1] Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.Alzheimers Dement. 2019 Oct;15(10):1333-1347. doi: 10.1016/j.jalz.2019.06.4950. Epub 2019 Aug 28.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] 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.
• [5] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.