Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4PGEVE)

• DOT Name: Cartilage acidic protein 1 (CRTAC1)
• Synonyms: 68 kDa chondrocyte-expressed protein; CEP-68; ASPIC
• Gene Name: CRTAC1
• Related Disease:
  Advanced cancer
  Aortic valve stenosis
  Osteoarthritis
  Polyarteritis nodosa
  Vasculitis due to ADA2 deficiency
  Neurofibromatosis type 1
  Lung carcinoma
• UniProt ID: CRAC1_HUMAN
• Pfam ID: PF07645 ; PF13517 ; PF07593
• Sequence:
  MAPSADPGMSRMLPFLLLLWFLPITEGSQRAEPMFTAVTNSVLPPDYDSNPTQLNYGVAV
  TDVDHDGDFEIVVAGYNGPNLVLKYDRAQKRLVNIAVDERSSPYYALRDRQGNAIGVTAC
  DIDGDGREEIYFLNTNNAFSGVATYTDKLFKFRNNRWEDILSDEVNVARGVASLFAGRSV
  ACVDRKGSGRYSIYIANYAYGNVGPDALIEMDPEASDLSRGILALRDVAAEAGVSKYTGG
  RGVSVGPILSSSASDIFCDNENGPNFLFHNRGDGTFVDAAASAGVDDPHQHGRGVALADF
  NRDGKVDIVYGNWNGPHRLYLQMSTHGKVRFRDIASPKFSMPSPVRTVITADFDNDQELE
  IFFNNIAYRSSSANRLFRVIRREHGDPLIEELNPGDALEPEGRGTGGVVTDFDGDGMLDL
  ILSHGESMAQPLSVFRGNQGFNNNWLRVVPRTRFGAFARGAKVVLYTKKSGAHLRIIDGG
  SGYLCEMEPVAHFGLGKDEASSVEVTWPDGKMVSRNVASGEMNSVLEILYPRDEDTLQDP
  APLECGQGFSQQENGHCMDTNECIQFPFVCPRDKPVCVNTYGSYRCRTNKKCSRGYEPNE
  DGTACVGTLGQSPGPRPTTPTAAAATAAAAAAAGAATAAPVLVDGDLNLGSVVKESCEPS
  C
• Tissue Specificity: Expressed in the interterritorial matrix of articular deep zone cartilage (at protein level). Isoform 1 and isoform 2 are expressed in brain. Isoform 1 is detected in lung and chondrocytes. Detected in cartilage, bone, cultured chondrocytes and lung, and at low levels in heart. Not detected in osteoblasts.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Aortic valve stenosis	DISW7AQ9	Strong	Genetic Variation	[2]
Osteoarthritis	DIS05URM	Strong	Biomarker	[3]
Polyarteritis nodosa	DISRQ5X8	Strong	Biomarker	[1]
Vasculitis due to ADA2 deficiency	DIS1UHPY	Strong	Biomarker	[1]
Neurofibromatosis type 1	DIS53JH9	moderate	Genetic Variation	[4]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[5]

2 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 Cartilage acidic protein 1 (CRTAC1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cartilage acidic protein 1 (CRTAC1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cartilage acidic protein 1 (CRTAC1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cartilage acidic protein 1 (CRTAC1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cartilage acidic protein 1 (CRTAC1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cartilage acidic protein 1 (CRTAC1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cartilage acidic protein 1 (CRTAC1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cartilage acidic protein 1 (CRTAC1).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cartilage acidic protein 1 (CRTAC1).	[14]

References

• [1] LOTUS: A single- and multitask machine learning algorithm for the prediction of cancer driver genes.PLoS Comput Biol. 2019 Sep 30;15(9):e1007381. doi: 10.1371/journal.pcbi.1007381. eCollection 2019 Sep.
• [2] Insights into the need for permanent pacemaker following implantation of the repositionable LOTUS valve for transcatheter aortic valve replacement in 250 patients: results from the REPRISE II trial with extended cohort.EuroIntervention. 2017 Sep 20;13(7):796-803. doi: 10.4244/EIJ-D-16-01025.
• [3] Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.PLoS One. 2016 Jul 14;11(7):e0159157. doi: 10.1371/journal.pone.0159157. eCollection 2016.
• [4] Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.Cancer Res. 2009 Sep 15;69(18):7393-401. doi: 10.1158/0008-5472.CAN-09-1752. Epub 2009 Sep 8.
• [5] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.