Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLBH2MA)

• DOT Name: Kinase D-interacting substrate of 220 kDa (KIDINS220)
• Synonyms: Ankyrin repeat-rich membrane-spanning protein
• Gene Name: KIDINS220
• Related Disease:
  Cerebral infarction
  Cognitive impairment
  Alzheimer disease
  Atopic dermatitis
  Behcet disease
  Benign prostatic hyperplasia
  Beta thalassemia
  Bladder cancer
  Breast cancer
  Childhood acute lymphoblastic leukemia
  Chronic renal failure
  Dementia
  Depression
  Familial Mediterranean fever
  Hepatitis B virus infection
  Intellectual disability
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Melanoma
  Neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Obesity
  Psychotic disorder
  Schizophrenia
  Spastic paraplegia, intellectual disability, nystagmus, and obesity
  Systemic lupus erythematosus
  Thyroid gland papillary carcinoma
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Ventriculomegaly and arthrogryposis
  Advanced cancer
  Age-related macular degeneration
  Asthma
  Breast carcinoma
  Colorectal carcinoma
  Prostate cancer
  Prostate carcinoma
  Rhabdomyosarcoma
  Rheumatoid arthritis
  Adenocarcinoma
  Castration-resistant prostate carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Hepatitis C virus infection
  Non-insulin dependent diabetes
• UniProt ID: KDIS_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF13637 ; PF07693
• Sequence:
  MSVLISQSVINYVEEENIPALKALLEKCKDVDERNECGQTPLMIAAEQGNLEIVKELIKN
  GANCNLEDLDNWTALISASKEGHVHIVEELLKCGVNLEHRDMGGWTALMWACYKGRTDVV
  ELLLSHGANPSVTGLYSVYPIIWAAGRGHADIVHLLLQNGAKVNCSDKYGTTPLVWAARK
  GHLECVKHLLAMGADVDQEGANSMTALIVAVKGGYTQSVKEILKRNPNVNLTDKDGNTAL
  MIASKEGHTEIVQDLLDAGTYVNIPDRSGDTVLIGAVRGGHVEIVRALLQKYADIDIRGQ
  DNKTALYWAVEKGNATMVRDILQCNPDTEICTKDGETPLIKATKMRNIEVVELLLDKGAK
  VSAVDKKGDTPLHIAIRGRSRKLAELLLRNPKDGRLLYRPNKAGETPYNIDCSHQKSILT
  QIFGARHLSPTETDGDMLGYDLYSSALADILSEPTMQPPICVGLYAQWGSGKSFLLKKLE
  DEMKTFAGQQIEPLFQFSWLIVFLTLLLCGGLGLLFAFTVHPNLGIAVSLSFLALLYIFF
  IVIYFGGRREGESWNWAWVLSTRLARHIGYLELLLKLMFVNPPELPEQTTKALPVRFLFT
  DYNRLSSVGGETSLAEMIATLSDACEREFGFLATRLFRVFKTEDTQGKKKWKKTCCLPSF
  VIFLFIIGCIISGITLLAIFRVDPKHLTVNAVLISIASVVGLAFVLNCRTWWQVLDSLLN
  SQRKRLHNAASKLHKLKSEGFMKVLKCEVELMARMAKTIDSFTQNQTRLVVIIDGLDACE
  QDKVLQMLDTVRVLFSKGPFIAIFASDPHIIIKAINQNLNSVLRDSNINGHDYMRNIVHL
  PVFLNSRGLSNARKFLVTSATNGDVPCSDTTGIQEDADRRVSQNSLGEMTKLGSKTALNR
  RDTYRRRQMQRTITRQMSFDLTKLLVTEDWFSDISPQTMRRLLNIVSVTGRLLRANQISF
  NWDRLASWINLTEQWPYRTSWLILYLEETEGIPDQMTLKTIYERISKNIPTTKDVEPLLE
  IDGDIRNFEVFLSSRTPVLVARDVKVFLPCTVNLDPKLREIIADVRAAREQISIGGLAYP
  PLPLHEGPPRAPSGYSQPPSVCSSTSFNGPFAGGVVSPQPHSSYYSGMTGPQHPFYNRPF
  FAPYLYTPRYYPGGSQHLISRPSVKTSLPRDQNNGLEVIKEDAAEGLSSPTDSSRGSGPA
  PGPVVLLNSLNVDAVCEKLKQIEGLDQSMLPQYCTTIKKANINGRVLAQCNIDELKKEMN
  MNFGDWHLFRSTVLEMRNAESHVVPEDPRFLSESSSGPAPHGEPARRASHNELPHTELSS
  QTPYTLNFSFEELNTLGLDEGAPRHSNLSWQSQTRRTPSLSSLNSQDSSIEISKLTDKVQ
  AEYRDAYREYIAQMSQLEGGPGSTTISGRSSPHSTYYMGQSSSGGSIHSNLEQEKGKDSE
  PKPDDGRKSFLMKRGDVIDYSSSGVSTNDASPLDPITEEDEKSDQSGSKLLPGKKSSERS
  SLFQTDLKLKGSGLRYQKLPSDEDESGTEESDNTPLLKDDKDRKAEGKVERVPKSPEHSA
  EPIRTFIKAKEYLSDALLDKKDSSDSGVRSSESSPNHSLHNEVADDSQLEKANLIELEDD
  SHSGKRGIPHSLSGLQDPIIARMSICSEDKKSPSECSLIASSPEENWPACQKAYNLNRTP
  STVTLNNNSAPANRANQNFDEMEGIRETSQVILRPSSSPNPTTIQNENLKSMTHKRSQRS
  SYTRLSKDPPELHAAASSESTGFGEERESIL
• Function: Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration. Modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway.
• Tissue Specificity: Abundant in developing and adult neural tissues as well as neuroendocrine cells and dendritic cells. Overexpressed in melanoma and melanoma cell lines.
• KEGG Pathway: Neurotrophin sig.ling pathway (hsa04722)
• Reactome Pathway:
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  ARMS-mediated activation (R-HSA-170984)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Altered Expression	[1]
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[4]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[5]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[6]
Beta thalassemia	DIS5RCQK	Strong	Genetic Variation	[7]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[8]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[9]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[10]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[11]
Dementia	DISXL1WY	Strong	Genetic Variation	[12]
Depression	DIS3XJ69	Strong	Genetic Variation	[13]
Familial Mediterranean fever	DISVP5WP	Strong	Genetic Variation	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[15]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[17]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[18]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[18]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[19]
Melanoma	DIS1RRCY	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[23]
Obesity	DIS47Y1K	Strong	Genetic Variation	[16]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[24]
Schizophrenia	DISSRV2N	Strong	Biomarker	[25]
Spastic paraplegia, intellectual disability, nystagmus, and obesity	DISGB8DX	Strong	Autosomal dominant	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Genetic Variation	[28]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[29]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[8]
Ventriculomegaly and arthrogryposis	DISD2F28	Strong	Autosomal recessive	[30]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[31]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[32]
Asthma	DISW9QNS	moderate	Altered Expression	[33]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[34]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[28]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[6]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[6]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[35]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[36]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[37]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[38]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[39]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[39]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[40]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[50]

3 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 decreases the methylation of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Kinase D-interacting substrate of 220 kDa (KIDINS220).	[48]

References

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