Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLPAX4N)

• DOT Name: Kinesin-like protein KIF2B (KIF2B)
• Gene Name: KIF2B
• Related Disease:
  High blood pressure
  Coronary atherosclerosis
  Coronary heart disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: KIF2B_HUMAN
• Pfam ID: PF00225
• Sequence:
  MASQFCLPESPCLSPLKPLKPHFGDIQEGIYVAIQRSDKRIHLAVVTEINRENYWVTVEW
  VEKAVKKGKKIDLETILLLNPALDSAEHPMPPPPLSPLALAPSSAIRDQRTATKWVAMIP
  QKNQTASGDSLDVRVPSKPCLMKQKKSPCLWEIQKLQEQREKRRRLQQEIRARRALDVNT
  RNPNYEIMHMIEEYRRHLDSSKISVLEPPQEHRICVCVRKRPLNQRETTLKDLDIITVPS
  DNVVMVHESKQKVDLTRYLQNQTFCFDHAFDDKASNELVYQFTAQPLVESIFRKGMATCF
  AYGQTGSGKTYTMGGDFSGTAQDCSKGIYALVAQDVFLLLRNSTYEKLDLKVYGTFFEIY
  GGKVYDLLNWKKKLQVLEDGNQQIQVVGLQEKEVCCVEEVLNLVEIGNSCRTSRQTPVNA
  HSSRSHAVFQIILKSGRIMHGKFSLVDLAGNERGADTTKASRKRQLEGAEINKSLLALKE
  CILALGQNKPHTPFRASKLTLVLRDSFIGQNSSTCMIATISPGMTSCENTLNTLRYANRV
  KKLNVDVRPYHRGHYPIGHEAPRMLKSHIGNSEMSLQRDEFIKIPYVQSEEQKEIEEVET
  LPTLLGKDTTISGKGSSQWLENIQERAGGVHHDIDFCIARSLSILEQKIDALTEIQKKLK
  LLLADLHVKSKVE
• Function: Plus end-directed microtubule-dependent motor required for spindle assembly and chromosome movement. Has microtubule depolymerization activity. Plays a role in chromosome congression.
• Tissue Specificity: Highest level in lung. High level in ovary, moderate levels in heart, kidney, placenta, skeletal muscle and spleen (at protein level). Pancreas and spleen express a shorter isoform (at protein level).
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Kinesins (R-HSA-983189)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	Strong	Genetic Variation	[1]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[2]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Kinesin-like protein KIF2B (KIF2B).	[4]

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 increases the methylation of Kinesin-like protein KIF2B (KIF2B).	[5]

References

• [1] Gene-environmental effects behind leukoaraiosis: a silent genetic variant of the kinesin protein can be activated in a subject with poorly controlled long-lasting hypertension.Clin Biochem. 2009 May;42(7-8):630-3. doi: 10.1016/j.clinbiochem.2008.11.003. Epub 2008 Nov 18.
• [2] Impact of KIF6 Polymorphism rs20455 on Coronary Heart Disease Risk and Effectiveness of Statin Therapy in 100 Patients from Southern Iran.Arch Iran Med. 2015 Oct;18(10):683-7.
• [3] Mutational landscape of candidate genes in familial prostate cancer.Prostate. 2014 Oct;74(14):1371-8. doi: 10.1002/pros.22849. Epub 2014 Aug 11.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] 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.