Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQAV541)

• DOT Name: Kinectin (KTN1)
• Synonyms: CG-1 antigen; Kinesin receptor
• Gene Name: KTN1
• Related Disease:
  Anxiety disorder
  Aplastic anemia
  Autoimmune disease
  Autosomal dominant nonsyndromic hearing loss 5
  Depression
  Hepatocellular carcinoma
  Neoplasm
  Schizophrenia
  Uveal Melanoma
  Stroke
  Type-1/2 diabetes
  Peroxisome biogenesis disorder
  Chronic renal failure
  Cutaneous squamous cell carcinoma
  End-stage renal disease
• UniProt ID: KTN1_HUMAN
• Pfam ID: PF05104
• Sequence:
  MEFYESAYFIVLIPSIVITVIFLFFWLFMKETLYDEVLAKQKREQKLIPTKTDKKKAEKK
  KNKKKEIQNGNLHESDSESVPRDFKLSDALAVEDDQVAPVPLNVVETSSSVRERKKKEKK
  QKPVLEEQVIKESDASKIPGKKVEPVPVTKQPTPPSEAAASKKKPGQKKSKNGSDDQDKK
  VETLMVPSKRQEALPLHQETKQESGSGKKKASSKKQKTENVFVDEPLIHATTYIPLMDNA
  DSSPVVDKREVIDLLKPDQVEGIQKSGTKKLKTETDKENAEVKFKDFLLSLKTMMFSEDE
  ALCVVDLLKEKSGVIQDALKKSSKGELTTLIHQLQEKDKLLAAVKEDAAATKDRCKQLTQ
  EMMTEKERSNVVITRMKDRIGTLEKEHNVFQNKIHVSYQETQQMQMKFQQVREQMEAEIA
  HLKQENGILRDAVSNTTNQLESKQSAELNKLRQDYARLVNELTEKTGKLQQEEVQKKNAE
  QAATQLKVQLQEAERRWEEVQSYIRKRTAEHEAAQQDLQSKFVAKENEVQSLHSKLTDTL
  VSKQQLEQRLMQLMESEQKRVNKEESLQMQVQDILEQNEALKAQIQQFHSQIAAQTSASV
  LAEELHKVIAEKDKQIKQTEDSLASERDRLTSKEEELKDIQNMNFLLKAEVQKLQALANE
  QAAAAHELEKMQQSVYVKDDKIRLLEEQLQHEISNKMEEFKILNDQNKALKSEVQKLQTL
  VSEQPNKDVVEQMEKCIQEKDEKLKTVEELLETGLIQVATKEEELNAIRTENSSLTKEVQ
  DLKAKQNDQVSFASLVEELKKVIHEKDGKIKSVEELLEAELLKVANKEKTVQDLKQEIKA
  LKEEIGNVQLEKAQQLSITSKVQELQNLLKGKEEQMNTMKAVLEEKEKDLANTGKWLQDL
  QEENESLKAHVQEVAQHNLKEASSASQFEELEIVLKEKENELKRLEAMLKERESDLSSKT
  QLLQDVQDENKLFKSQIEQLKQQNYQQASSFPPHEELLKVISEREKEISGLWNELDSLKD
  AVEHQRKKNNDLREKNWEAMEALASTEKMLQDKVNKTSKERQQQVEAVELEAKEVLKKLF
  PKVSVPSNLSYGEWLHGFEKKAKECMAGTSGSEEVKVLEHKLKEADEMHTLLQLECEKYK
  SVLAETEGILQKLQRSVEQEENKWKVKVDESHKTIKQMQSSFTSSEQELERLRSENKDIE
  NLRREREHLEMELEKAEMERSTYVTEVRELKDLLTELQKKLDDSYSEAVRQNEELNLLKA
  QLNETLTKLRTEQNERQKVAGDLHKAQQSLELIQSKIVKAAGDTTVIENSDVSPETESSE
  KETMSVSLNQTVTQLQQLLQAVNQQLTKEKEHYQVLE
• Function: Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin.
• Tissue Specificity: High levels in peripheral blood lymphocytes, testis and ovary, lower levels in spleen, thymus, prostate, small intestine and colon.
• Reactome Pathway:
  RHO GTPases activate KTN1 (R-HSA-5625970)
  Post-translational protein phosphorylation (R-HSA-8957275)
  RHOA GTPase cycle (R-HSA-8980692)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOG GTPase cycle (R-HSA-9013408)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety disorder	DISBI2BT	Definitive	Biomarker	[1]
Aplastic anemia	DISJRSC0	Definitive	Biomarker	[2]
Autoimmune disease	DISORMTM	Definitive	Biomarker	[2]
Autosomal dominant nonsyndromic hearing loss 5	DISZ795Z	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Schizophrenia	DISSRV2N	Strong	Biomarker	[7]
Uveal Melanoma	DISA7ZGL	Strong	Genetic Variation	[8]
Stroke	DISX6UHX	moderate	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[9]
Peroxisome biogenesis disorder	DISBQ6QJ	Disputed	Genetic Variation	[10]
Chronic renal failure	DISGG7K6	Limited	Biomarker	[11]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[12]
End-stage renal disease	DISXA7GG	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Kinectin (KTN1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Kinectin (KTN1).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Kinectin (KTN1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Kinectin (KTN1).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kinectin (KTN1).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinectin (KTN1).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kinectin (KTN1).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Kinectin (KTN1).	[18]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Kinectin (KTN1).	[19]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Kinectin (KTN1).	[20]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Kinectin (KTN1).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Kinectin (KTN1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Kinectin (KTN1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Kinectin (KTN1).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Kinectin (KTN1).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Kinectin (KTN1).	[26]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Kinectin (KTN1).	[27]

References

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• [10] Peroxisome biogenesis and molecular defects in peroxisome assembly disorders.Cell Biochem Biophys. 2000;32 Spring:155-64. doi: 10.1385/cbb:32:1-3:155.
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• [19] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [20] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
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• [25] 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.
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