Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTSRY39)

• DOT Name: Guided entry of tail-anchored proteins factor CAMLG (CAMLG)
• Synonyms: Calcium signal-modulating cyclophilin ligand
• Gene Name: CAMLG
• Related Disease:
  Adult lymphoma
  Lymphoma
  Pediatric lymphoma
  Breast cancer
  Breast carcinoma
  Common variable immunodeficiency
  leukaemia
  Leukemia
  Melanoma
  Acute myelogenous leukaemia
  Congenital disorder of glycosylation, type IIz
• UniProt ID: CAMLG_HUMAN
• PDB ID: 6SO5; 8CR1
• Pfam ID: PF14963
• Sequence:
  MESMAVATDGGERPGVPAGSGLSASQRRAELRRRKLLMNSEQRINRIMGFHRPGSGAEEE
  SQTKSKQQDSDKLNSLSVPSVSKRVVLGDSVSTGTTDQQGGVAEVKGTQLGDKLDSFIKP
  PECSSDVNLELRQRNRGDLTADSVQRGSRHGLEQYLSRFEEAMKLRKQLISEKPSQEDGN
  TTEEFDSFRIFRLVGCALLALGVRAFVCKYLSIFAPFLTLQLAYMGLYKYFPKSEKKIKT
  TVLTAALLLSGIPAEVINRSMDTYSKMGEVFTDLCVYFFTFIFCHELLDYWGSEVP
• Function: Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. Required for the stability of GET1. Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium. Essential for the survival of peripheral follicular B cells.
• Tissue Specificity: Ubiquitous. Highest levels in brain, testis and ovary.
• Reactome Pathway: Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Altered Expression	[1]
Lymphoma	DISN6V4S	Definitive	Altered Expression	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Common variable immunodeficiency	DISHE7JQ	Strong	Genetic Variation	[3]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Melanoma	DIS1RRCY	moderate	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[5]
Congenital disorder of glycosylation, type IIz	DIS6FSR4	Limited	Autosomal recessive	[6]

9 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 Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[15]

1 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 Guided entry of tail-anchored proteins factor CAMLG (CAMLG).	[12]

References

• [1] A proliferation-inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase-regulated mammalian target of rapamycin activation.Blood. 2009 May 21;113(21):5206-16. doi: 10.1182/blood-2008-09-179762. Epub 2009 Mar 25.
• [2] CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways.Breast Cancer Res Treat. 2011 Nov;130(1):19-27. doi: 10.1007/s10549-010-1274-4. Epub 2010 Dec 3.
• [3] Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes.J Allergy Clin Immunol. 2007 Nov;120(5):1178-85. doi: 10.1016/j.jaci.2007.10.001.
• [4] A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells.Cancer Lett. 2013 Oct 1;339(1):93-101. doi: 10.1016/j.canlet.2013.07.019. Epub 2013 Jul 20.
• [5] Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis.Haematologica. 2002 Jun;87(6):569-77.
• [6] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.