Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWO612W)

• DOT Name: Leucine-rich repeat and guanylate kinase domain-containing protein (LRGUK)
• Gene Name: LRGUK
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: LRGUK_HUMAN
• Pfam ID: PF00625 ; PF12799 ; PF14580
• Sequence:
  MATSERALLRTRAASLLRGLGRSRTGARSLQFRAEKERQPCWSFPMGQKTKGSSNIASSY
  LLQQLMHRYQELDSDGDEDQGEGEAGSEESSESEMLNLEEEFDGVLREEAVAKALHHLGR
  SGSGTEQVYLNLTLSGCNLIDVSILCGYVHLQKLDLSANKIEDLSCVSCMPYLLELNASQ
  NNLTTFFNFKPPKNLKKADFSHNQISEICDLSAYHALTKLILDGNEIEEISGLEMCNNLI
  HLSLANNKITTINGLNKLPIKILCLSNNQIEMITGLEDLKALQNLDLSHNQISSLQGLEN
  HDLLEVINLEDNKIAELREIEYIKNLPILRVLNLLENPIQEKSEYWFFVIFMLLRLTELD
  QKKIKVEEKVSAVNKYDPPPEVVAAQDHLTHVVNSVMQPQRIFDSTLPSLDAPYPMLILA
  GPEACGKRELAHRLCRQFSTYFRYGACHTTRPPYFGEGDRVDYHFISQDVFDEMVNMGKF
  ILTFSYGNHKYGLNRDTVEGIARDGLASCIHMEIEGVRSLKYSYFEPRYILVVPMNKEKY
  EGYLRRKGLFSRAEIEFAVSRVDLYIKINQNFPGYFDEVINADDLDVAYQKLSQLIREYL
  GLTEEPAKSLATTADVKTSHLKPEAHPTKYISSNMGDFLHSTDRNYLIKFWAKLSAKKTP
  AERDSIHRQHEAARQALMGRIRPDHTLLFQRGPVPAPLTSGLHYYTTLEELWKSFDLCED
  YFKPPFGPYPEKSGKDSLVSMKCSLFRFCPWSKELPFQPPEGSISSHLGSGASDSETEET
  RKALPIQSFSHEKESHQHRQHSVPVISRPGSNVKPTLPPIPQGRR
• Function: Involved in multiple aspects of sperm assembly including acrosome attachment, shaping of the sperm head and in the early aspects of axoneme development. Not essential for primary cilium biogenesis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Leucine-rich repeat and guanylate kinase domain-containing protein (LRGUK).	[2]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Leucine-rich repeat and guanylate kinase domain-containing protein (LRGUK).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Leucine-rich repeat and guanylate kinase domain-containing protein (LRGUK).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Leucine-rich repeat and guanylate kinase domain-containing protein (LRGUK).	[5]

References

• [1] Polymorphisms near EXOC4 and LRGUK on chromosome 7q32 are associated with Type 2 Diabetes and fasting glucose; the NHLBI Family Heart Study.BMC Med Genet. 2008 May 22;9:46. doi: 10.1186/1471-2350-9-46.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.