Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0NIKYM)

• DOT Name: Cyclin-L2 (CCNL2)
• Synonyms: Paneth cell-enhanced expression protein
• Gene Name: CCNL2
• Related Disease:
  Lung adenocarcinoma
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Gallbladder cancer
  Hepatocellular carcinoma
  High blood pressure
  Neoplasm
  Syndactyly-telecanthus-anogenital and renal malformations syndrome
  Chronic obstructive pulmonary disease
  Familial primary hypomagnesemia
• UniProt ID: CCNL2_HUMAN
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MAAAAAAAGAAGSAAPAAAAGAPGSGGAPSGSQGVLIGDRLYSGVLITLENCLLPDDKLR
  FTPSMSSGLDTDTETDLRVVGCELIQAAGILLRLPQVAMATGQVLFQRFFYTKSFVKHSM
  EHVSMACVHLASKIEEAPRRIRDVINVFHRLRQLRDKKKPVPLLLDQDYVNLKNQIIKAE
  RRVLKELGFCVHVKHPHKIIVMYLQVLECERNQHLVQTSWNYMNDSLRTDVFVRFQPESI
  ACACIYLAARTLEIPLPNRPHWFLLFGATEEEIQEICLKILQLYARKKVDLTHLEGEVEK
  RKHAIEEAKAQARGLLPGGTQVLDGTSGFSPAPKLVESPKEGKGSKPSPLSVKNTKRRLE
  GAKKAKADSPVNGLPKGRESRSRSRSREQSYSRSPSRSASPKRRKSDSGSTSGGSKSQSR
  SRSRSDSPPRQAPRSAPYKGSEIRGSRKSKDCKYPQKPHKSRSRSSSRSRSRSRERADNP
  GKYKKKSHYYRDQRRERSRSYERTGRRYERDHPGHSRHRR
• Function: Involved in pre-mRNA splicing. May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Gallbladder cancer	DISXJUAF	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[5]
High blood pressure	DISY2OHH	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Syndactyly-telecanthus-anogenital and renal malformations syndrome	DISZA8BN	Strong	Genetic Variation	[6]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[7]
Familial primary hypomagnesemia	DIS6TTKI	moderate	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cyclin-L2 (CCNL2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-L2 (CCNL2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cyclin-L2 (CCNL2).	[10]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Cyclin-L2 (CCNL2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cyclin-L2 (CCNL2).	[12]

References

• [1] Overexpression of cyclin L2 induces apoptosis and cell-cycle arrest in human lung cancer cells.Chin Med J (Engl). 2007 May 20;120(10):905-9.
• [2] Molecular function and biological importance of CNNM family Mg2+ transporters.J Biochem. 2019 Mar 1;165(3):219-225. doi: 10.1093/jb/mvy095.
• [3] Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library.Oncotarget. 2018 Jan 1;9(26):18559-18569. doi: 10.18632/oncotarget.24963. eCollection 2018 Apr 6.
• [4] miR-433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M.Oncol Lett. 2018 Mar;15(3):3305-3312. doi: 10.3892/ol.2017.7708. Epub 2017 Dec 28.
• [5] Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells.J Biol Chem. 2004 Mar 19;279(12):11639-48. doi: 10.1074/jbc.M312895200. Epub 2003 Dec 17.
• [6] STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis.Cell Cycle. 2016;15(5):678-88. doi: 10.1080/15384101.2016.1147632.
• [7] Upregulation of MicroRNA-214 Contributes to the Development of Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension Via Targeting CCNL2.Sci Rep. 2016 Jul 6;6:24661. doi: 10.1038/srep24661.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.