Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3UWL7D)

• DOT Name: Chromosome-associated kinesin KIF4A (KIF4A)
• Synonyms: Chromokinesin-A
• Gene Name: KIF4A
• Related Disease:
  Ependymoma
  Epilepsy
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Adult glioblastoma
  Advanced cancer
  Castration-resistant prostate carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Neoplasm
  Oral cancer
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Triple negative breast cancer
  Colorectal carcinoma
  Hepatitis B virus infection
  Intellectual disability, X-linked 100
  Lung cancer
  Lung carcinoma
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Intellectual disability
  Intellectual disability, autosomal dominant 40
  Meningioma
• UniProt ID: KIF4A_HUMAN
• PDB ID: 6OYL
• Pfam ID: PF00225
• Sequence:
  MKEEVKGIPVRVALRCRPLVPKEISEGCQMCLSFVPGEPQVVVGTDKSFTYDFVFDPSTE
  QEEVFNTAVAPLIKGVFKGYNATVLAYGQTGSGKTYSMGGAYTAEQENEPTVGVIPRVIQ
  LLFKEIDKKSDFEFTLKVSYLEIYNEEILDLLCPSREKAQINIREDPKEGIKIVGLTEKT
  VLVALDTVSCLEQGNNSRTVASTAMNSQSSRSHAIFTISLEQRKKSDKNSSFRSKLHLVD
  LAGSERQKKTKAEGDRLKEGININRGLLCLGNVISALGDDKKGGFVPYRDSKLTRLLQDS
  LGGNSHTLMIACVSPADSNLEETLNTLRYADRARKIKNKPIVNIDPQTAELNHLKQQVQQ
  LQVLLLQAHGGTLPGSITVEPSENLQSLMEKNQSLVEENEKLSRGLSEAAGQTAQMLERI
  ILTEQANEKMNAKLEELRQHAACKLDLQKLVETLEDQELKENVEIICNLQQLITQLSDET
  VACMAAAIDTAVEQEAQVETSPETSRSSDAFTTQHALRQAQMSKELVELNKALALKEALA
  RKMTQNDSQLQPIQYQYQDNIKELELEVINLQKEKEELVLELQTAKKDANQAKLSERRRK
  RLQELEGQIADLKKKLNEQSKLLKLKESTERTVSKLNQEIRMMKNQRVQLMRQMKEDAEK
  FRQWKQKKDKEVIQLKERDRKRQYELLKLERNFQKQSNVLRRKTEEAAAANKRLKDALQK
  QREVADKRKETQSRGMEGTAARVKNWLGNEIEVMVSTEEAKRHLNDLLEDRKILAQDVAQ
  LKEKKESGENPPPKLRRRTFSLTEVRGQVSESEDSITKQIESLETEMEFRSAQIADLQQK
  LLDAESEDRPKQRWENIATILEAKCALKYLIGELVSSKIQVSKLESSLKQSKTSCADMQK
  MLFEERNHFAEIETELQAELVRMEQQHQEKVLYLLSQLQQSQMAEKQLEESVSEKEQQLL
  STLKCQDEELEKMREVCEQNQQLLRENEIIKQKLTLLQVASRQKHLPKDTLLSPDSSFEY
  VPPKPKPSRVKEKFLEQSMDIEDLKYCSEHSVNEHEDGDGDDDEGDDEEWKPTKLVKVSR
  KNIQGCSCKGWCGNKQCGCRKQKSDCGVDCCCDPTKCRNRQQGKDSLGTVERTQDSEGSF
  KLEDPTEVTPGLSFFNPVCATPNSKILKEMCDVEQVLSKKTPPAPSPFDLPELKHVATEY
  QENKAPGKKKKRALASNTSFFSGCSPIEEEAH
• Function: Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis. Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis. May play a role in mitotic chromosomal positioning and bipolar spindle stabilization.
• Tissue Specificity: Highly expressed in hematopoietic tissues, fetal liver, spleen, thymus and adult thymus and bone marrow. Lower levels are found in heart, testis, kidney, colon and lung.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  Recycling pathway of L1 (R-HSA-437239)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Kinesins (R-HSA-983189)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ependymoma	DISUMRNZ	Definitive	Biomarker	[1]
Epilepsy	DISBB28L	Definitive	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Oral cancer	DISLD42D	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[10]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[6]
Hepatitis B virus infection	DISLQ2XY	moderate	Altered Expression	[12]
Intellectual disability, X-linked 100	DISX6CQ7	Moderate	X-linked	[13]
Lung cancer	DISCM4YA	moderate	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[3]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[14]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[14]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[15]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[15]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[16]
Intellectual disability, autosomal dominant 40	DISAI0IH	Limited	X-linked recessive	[16]
Meningioma	DISPT4TG	Limited	Altered Expression	[17]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Chromosome-associated kinesin KIF4A (KIF4A) affects the response to substance of Vinblastine.	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Chromosome-associated kinesin KIF4A (KIF4A).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Chromosome-associated kinesin KIF4A (KIF4A).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chromosome-associated kinesin KIF4A (KIF4A).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Chromosome-associated kinesin KIF4A (KIF4A).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Chromosome-associated kinesin KIF4A (KIF4A).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Chromosome-associated kinesin KIF4A (KIF4A).	[46]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Chromosome-associated kinesin KIF4A (KIF4A).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[25]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[28]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[28]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[29]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[30]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[31]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[32]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[33]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[34]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[35]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[36]
Epanova	DMHEAGL	Approved	Epanova decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[37]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[38]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[43]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[45]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Chromosome-associated kinesin KIF4A (KIF4A).	[47]

References

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