Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0X95YA)

• DOT Name: Protein cramped-like (CRAMP1)
• Synonyms: Cramped chromatin regulator homolog 1; Hematological and neurological expressed 1-like protein
• Gene Name: CRAMP1
• Related Disease:
  Atrial fibrillation
  Epilepsy
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Triple negative breast cancer
• UniProt ID: CRML_HUMAN
• Sequence:
  MTVKLGDGGSGEDGLKKLGKRAADEESLEGEGAGGADAAEESSGTKRDEKTPRAGADGPP
  APPGAPQAPSPPQGSPQDQHHFLRSSVRPQSKRPRKDPPSAVGSGNAGGSGPRGKGAEGG
  GSSSGNVSGVAPAAPAGGSRSSSRNLGSSGGEKEEGKKVRRQWESWSTEDKNTFFEGLYE
  HGKDFEAIQNNIALKYKKKGKPASMVKNKEQVRHFYYRTWHKITKYIDFDHVFSRGLKKS
  SQELYGLICYGELRKKIGGCMDDKNATKLNELIQVGATTVRYKGRNLRIKAPMCRALKKL
  CDPDGLSDEEDQKPVRLPLKVPIELQPRNNHAWARVQSLAQNPRLRMIVELHRKVSSLIE
  FLKQKWALHEVRVRKTLEERQLQDSCSAPMQEKVTLHLFPGENCTLTPLPGVARVVHSKA
  FCTVHWQEGGRCKQSAKDAHVLPPAQILGIQSGQGTARGQVKCPRSGAEGKGVGRPPPAA
  DALQSSGESSPESAPGEGAALSLSSPDAPDRPPPRHQDTGPCLEKTPAEGRDSPTREPGA
  LPCACGQLPDLEDELSLLDPLPRYLKSCQDLIVPEQCRCADTRPGSEQPPLGGAASPEVL
  APVSKEAADLAPTGPSPRPGPGLLLDVCTKDLADAPAEELQEKGSPAGPPPSQGQPAARP
  PKEVPASRLAQQLREEGWNLQTSESLTLAEVYLMMGKPSKLQLEYDWLGPGRQDPRPGSL
  PTALHKQRLLSCLLKLISTEVNPKLALEANTISTASVRPAQEEQSMTPPGKVVTVSSRSP
  RCPRNQASLRSSKTFPPSSAPCSSGLRNPPRPLLVPGPSSTGSNDSDGGLFAVPTTLPPN
  SRHGKLFSPSKEAELTFRQHLNSISMQSDFFLPKPRKLRNRHLRKPLVVQRTLLPRPSEN
  QSHNVCSFSILSNSSVTGRGSFRPIQSSLTKAALSRPIVPKVLPPQATSHLASAIDLAAT
  SAGILSGNPLPALDTEGLSGISPLSSDEVTGAISGQDSTGTHQDGDTLPTVGGSDPFVSI
  PSRPEQEPVADSFQGSSVLSLSELPKAPLQNGLSIPLSSSESSSTRLSPPDVSALLDISL
  PGPPEDALSQGEPATHISDSIIEIAISSGQYGEGVPLSPAKLNGSDSSKSLPSPSSSPQP
  HWIASPTHDPQWYPSDSTDSSLSSLFASFISPEKSRKMLPTPIGTNSGTSLLGPSLLDGN
  SRDSFVSRSLADVAEVVDSQLVCMMNENSIDYISRFNDLAQELSIAEPGRREALFDGGGG
  GPAVSDLSQ

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Epilepsy	DISBB28L	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[5]

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 Protein cramped-like (CRAMP1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein cramped-like (CRAMP1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein cramped-like (CRAMP1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein cramped-like (CRAMP1).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Protein cramped-like (CRAMP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein cramped-like (CRAMP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein cramped-like (CRAMP1).	[11]

References

• [1] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [2] GWAS identifies two susceptibility loci for lamotrigine-induced skin rash in patients with epilepsy.Epilepsy Res. 2015 Sep;115:88-94. doi: 10.1016/j.eplepsyres.2015.05.014. Epub 2015 Jun 2.
• [3] HN1L-mediated transcriptional axis AP-2/METTL13/TCF3-ZEB1 drives tumor growth and metastasis in hepatocellular carcinoma.Cell Death Differ. 2019 Nov;26(11):2268-2283. doi: 10.1038/s41418-019-0301-1. Epub 2019 Feb 18.
• [4] Overexpression of HN1L promotes cell malignant proliferation in non-small cell lung cancer.Cancer Biol Ther. 2017 Nov 2;18(11):904-915. doi: 10.1080/15384047.2017.1385678. Epub 2017 Oct 20.
• [5] HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway.Stem Cell Reports. 2018 Jan 9;10(1):212-227. doi: 10.1016/j.stemcr.2017.11.010. Epub 2017 Dec 14.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.