Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF4K46N)

• DOT Name: SPOC domain-containing protein 1 (SPOCD1)
• Gene Name: SPOCD1
• Related Disease:
  Glioma
  Neoplasm
  Urinary bladder cancer
  Bone osteosarcoma
  Gastric cancer
  Osteosarcoma
  Stomach cancer
• UniProt ID: SPOC1_HUMAN
• Pfam ID: PF07744 ; PF07500
• Sequence:
  MSQAGDVEGPSTGDPVLSPQHNCELLQNMEGASSMPGLSPDGPGASSGPGVRAGSRRKIP
  RKEALRGGSSRAAGAAEVRPGVLELLAVVQSRGSMLAPGLHMQLPSVPTQGRALTSKRLQ
  VSLCDILDDSCPRKLCSRSAGLPERALACRERLAGVEEVSCLRPREARDGGMSSPGCDRR
  SPTLSKEEPPGRPLTSSPDPVPVRVRKKWRRQGAHSECEEGAGDFLWLDQSPRGDNLLSV
  GDPPQVADLESLGGPCRPPSPKDTGSGPGEPGGSGAGCASGTEKFGYLPATGDGPQPGSP
  CGPVGFPVPSGGESLSSAAQAPPQSAALCLGASAQASAEQQEAVCVVRTGSDEGQAPAQD
  QEELEAKAQPASRGRLEQGLAAPADTCASSREPLGGLSSSLDTEASRACSGPFMEQRRSK
  GTKNLKKGPVPCAQDRGTDRSSDNSHQDRPEEPSPGGCPRLEEVKIPHGVKLVCYLGSGP
  VIQLLGAISHGQAGGQLPPKLEVLEDLMEVSSPSPAQRLRRKKRPMVQGPAGCQVFQPSP
  SGGTAGDPGGLSDPFYPPRSGSLALGDPSSDPACSQSGPMEAEEDSLPEQPEDSAQLQQE
  KPSLYIGVRGTVVRSMQEVLWTRLRELPDPVLSEEVVEGIAAGIEAALWDLTQGTNGRYK
  TKYRSLLFNLRDPRNLDLFLKVVHGDVTPYDLVRMSSMQLAPQELARWRDQEEKRGLNII
  EQQQKEPCRLPASKMTHKGEVEIQRDMDQTLTLEDLVGPQMFMDCSPQALPIASEDTTGQ
  HDHHFLDPNCHICKDWEPSNELLGSFEAAKSCGDNIFQKALSQTPMPAPEMPKTRELSPT
  EPQDRVPPSGLHVPAAPTKALPCLPPWEGVLDMFSIKRFRARAQLVSGHSCRLVQALPTV
  IRSAGCIPSNIVWDLLASICPAKAKDVCVVRLCPHGARDTQNCRLLYSYLNDRQRHGLAS
  VEHMGMVLLPLPAFQPLPTRLRPLGGPGLWALPVSPLLSPGLEVTHSSLLLAVLLPKEGL
  PDTAGSSPWLGKVQKMVSFNSKVEKRYYQPDDRRPNVPLKGTPPPGGAWQQSQGRGSIAP
  RGISAWQRPPRGRGRLWPEPENWQHPGRGQWPPEPGLRQSQHPYSVAPAGHGFGRGQHFH
  RDSCPHQALLRHLESLATMSHQLQALLCPQTKSSIPRPLQRLSSALAAPEPPGPARDSSL
  GPTDEAGSECPFPRKA
• Function: Essential excecutor of PIWIL4-piRNA pathway directed transposon DNA methylation and silencing in the male embryonic germ cells. Associates with the de novo DNA methylation machinery and repressive chromatin remodeling complexes. Tethering of PIWIL4 to a nascent transposable element transcript recruits repressive chromatin remodeling activities and the de novo methylation apparatus through SPOCD1. Not required for piRNA biosynthesis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[2]
Gastric cancer	DISXGOUK	moderate	Genetic Variation	[3]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[2]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of SPOC domain-containing protein 1 (SPOCD1).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[14]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SPOC domain-containing protein 1 (SPOCD1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SPOC domain-containing protein 1 (SPOCD1).	[20]

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 increases the methylation of SPOC domain-containing protein 1 (SPOCD1).	[16]

References

• [1] SPOCD1 promotes the proliferation and metastasis of glioma cells by up-regulating PTX3.Am J Cancer Res. 2018 Apr 1;8(4):624-635. eCollection 2018.
• [2] SPOCD1 promotes cell proliferation and inhibits cell apoptosis in human osteosarcoma.Mol Med Rep. 2018 Feb;17(2):3218-3225. doi: 10.3892/mmr.2017.8263. Epub 2017 Dec 12.
• [3] Exome Array Analysis Identifies Variants in SPOCD1 and BTN3A2 That Affect Risk for Gastric Cancer.Gastroenterology. 2017 Jun;152(8):2011-2021. doi: 10.1053/j.gastro.2017.02.017. Epub 2017 Feb 27.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
• [13] 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.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [15] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [16] 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.
• [17] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [20] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.