Details of Drug Off-Target (DOT)

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

• DOT Name: Serine/threonine-protein kinase ICK (CILK1)
• Synonyms: EC 2.7.11.1; Ciliogenesis associated kinase 1; Intestinal cell kinase; hICK; Laryngeal cancer kinase 2; LCK2; MAK-related kinase; MRK
• Gene Name: CILK1
• Related Disease:
  Breast carcinoma
  Melanoma
  Thyroid gland papillary carcinoma
  Adenoma
  Advanced cancer
  B-cell neoplasm
  Bladder cancer
  Breast neoplasm
  Cerebellar ataxia
  Ciliopathy
  Cleft palate
  Colon cancer
  Colon carcinoma
  Endocrine-cerebro-osteodysplasia syndrome
  Fibrosarcoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Isolated cleft palate
  Lung cancer
  Lung carcinoma
  Matthew-Wood syndrome
  Medulloblastoma
  Non-small-cell lung cancer
  Osteoporosis
  Polydactyly
  T-cell leukaemia
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Ductal breast carcinoma in situ
  Glioblastoma multiforme
  Osteoarthritis
  Triple negative breast cancer
  Juvenile myoclonic epilepsy
  Breast cancer
  Cutaneous melanoma
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Childhood acute lymphoblastic leukemia
  Congenital contractural arachnodactyly
  Pancreatic cancer
  Pneumonia
  Short rib-polydactyly syndrome
• UniProt ID: CILK1_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MNRYTTIRQLGDGTYGSVLLGRSIESGELIAIKKMKRKFYSWEECMNLREVKSLKKLNHA
  NVVKLKEVIRENDHLYFIFEYMKENLYQLIKERNKLFPESAIRNIMYQILQGLAFIHKHG
  FFHRDLKPENLLCMGPELVKIADFGLAREIRSKPPYTDYVSTRWYRAPEVLLRSTNYSSP
  IDVWAVGCIMAEVYTLRPLFPGASEIDTIFKICQVLGTPKKTDWPEGYQLSSAMNFRWPQ
  CVPNNLKTLIPNASSEAVQLLRDMLQWDPKKRPTASQALRYPYFQVGHPLGSTTQNLQDS
  EKPQKGILEKAGPPPYIKPVPPAQPPAKPHTRISSRQHQASQPPLHLTYPYKAEVSRTDH
  PSHLQEDKPSPLLFPSLHNKHPQSKITAGLEHKNGEIKPKSRRRWGLISRSTKDSDDWAD
  LDDLDFSPSLSRIDLKNKKRQSDDTLCRFESVLDLKPSEPVGTGNSAPTQTSYQRRDTPT
  LRSAAKQHYLKHSRYLPGISIRNGILSNPGKEFIPPNPWSSSGLSGKSSGTMSVISKVNS
  VGSSSTSSSGLTGNYVPSFLKKEIGSAMQRVHLAPIPDPSPGYSSLKAMRPHPGRPFFHT
  QPRSTPGLIPRPPAAQPVHGRTDWASKYASRR
• Function: Required for ciliogenesis. Phosphorylates KIF3A. Involved in the control of ciliary length. Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips. May play a key role in the development of multiple organ systems and particularly in cardiac development. Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity.
• Tissue Specificity: Expressed in heart, brain, placenta, pancreas, thymus, prostate, testis, ovary, small intestine and colon, with highest levels in placenta and testis. Not detected in spleen. Also expressed in many cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[3]
Adenoma	DIS78ZEV	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[9]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[10]
Cleft palate	DIS6G5TF	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Endocrine-cerebro-osteodysplasia syndrome	DIS9Y3MA	Strong	Autosomal recessive	[13]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[16]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[17]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[19]
Osteoporosis	DISF2JE0	Strong	Biomarker	[20]
Polydactyly	DIS25BMZ	Strong	Biomarker	[13]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[21]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[7]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[23]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[24]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[25]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[26]
Juvenile myoclonic epilepsy	DISYXV1N	Supportive	Autosomal dominant	[27]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[1]
Cutaneous melanoma	DIS3MMH9	Disputed	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[28]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[28]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Altered Expression	[28]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Genetic Variation	[29]
Pancreatic cancer	DISJC981	Limited	Biomarker	[30]
Pneumonia	DIS8EF3M	Limited	Genetic Variation	[31]
Short rib-polydactyly syndrome	DISY2RES	Limited	Genetic Variation	[32]

1 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 Serine/threonine-protein kinase ICK (CILK1).	[33]

10 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 Serine/threonine-protein kinase ICK (CILK1).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine/threonine-protein kinase ICK (CILK1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine/threonine-protein kinase ICK (CILK1).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine/threonine-protein kinase ICK (CILK1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Serine/threonine-protein kinase ICK (CILK1).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine/threonine-protein kinase ICK (CILK1).	[39]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Serine/threonine-protein kinase ICK (CILK1).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine/threonine-protein kinase ICK (CILK1).	[41]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine/threonine-protein kinase ICK (CILK1).	[42]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Serine/threonine-protein kinase ICK (CILK1).	[43]

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