Details of Drug Off-Target (DOT)

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

• DOT Name: Sperm-associated antigen 16 protein (SPAG16)
• Synonyms: Pf20 protein homolog
• Gene Name: SPAG16
• Related Disease:
  Attention deficit hyperactivity disorder
  Chronic obstructive pulmonary disease
  Male infertility
  Neoplasm
  Pneumonitis
  Vascular dementia
  Pemphigus vulgaris
  Rheumatoid arthritis
• UniProt ID: SPG16_HUMAN
• Pfam ID: PF00400
• Sequence:
  MAAQRGMPSSAVRVLEEALGMGLTAAGDARDTADAVAAEGAYYLEQVTITEASEDDYEYE
  EIPDDNFSIPEGEEDLAKAIQMAQEQATDTEILERKTVLPSKHAVPEVIEDFLCNFLIKM
  GMTRTLDCFQSEWYELIQKGVTELRTVGNVPDVYTQIMLLENENKNLKKDLKHYKQAADK
  AREDLLKIQKERDFHRMHHKRIVQEKNKLINDLKGLKLHYASYEPTIRVLHEKHHTLLKE
  KMLTSLERDKVVGQISGLQETLKKLQRGHSYHGPQIKVDHSREKENAPEGPTQKGLREAR
  EQNKCKTKMKGNTKDSEFPIDMQPNPNLNVSKESLSPAKFDYKLKNIFRLHELPVSCVSM
  QPHKDILVSCGEDRLWKVLGLPKCNVLLTGFGHTDWLSDCCFHPSGDKLATSSGDTTVKL
  WDLCKGDCILTFEGHSRAVWSCTWHSCGNFVASSSLDKTSKIWDVNSERCRCTLYGHTDS
  VNSIEFFPFSNTLLTSSADKTLSIWDARTGICEQSLYGHMHSINDAIFDPRGHMIASCDA
  CGVTKLWDFRKLLPIVSIDIGPSPGNEVNFDSSGRVLAQASGNGVIHLLDLKSGEIHKLM
  GHENEAHTVVFSHDGEILFSGGSDGTVRTWS
• Function: Necessary for sperm flagellar function. Plays a role in motile ciliogenesis. May help to recruit STK36 to the cilium or apical surface of the cell to initiate subsequent steps of construction of the central pair apparatus of motile cilia.
• Tissue Specificity: Isoform 1 is detected in testis. Isoform 4 is detected in testis and brain, and at lower levels in kidney, heart, pancreas, thyroid, ovary, adrenal gland, spinal cord, trachea and liver.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Pneumonitis	DIS88E0K	Strong	Biomarker	[5]
Vascular dementia	DISVO82H	Strong	Biomarker	[6]
Pemphigus vulgaris	DISENR62	moderate	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Sperm-associated antigen 16 protein (SPAG16) affects the response to substance of NAPQI.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Sperm-associated antigen 16 protein (SPAG16).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Sperm-associated antigen 16 protein (SPAG16).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Sperm-associated antigen 16 protein (SPAG16).	[13]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Sperm-associated antigen 16 protein (SPAG16).	[17]

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 Sperm-associated antigen 16 protein (SPAG16).	[18]

References

• [1] Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.Nat Genet. 2019 Jan;51(1):63-75. doi: 10.1038/s41588-018-0269-7. Epub 2018 Nov 26.
• [2] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [3] Genetic variation in SPAG16 regions encoding the WD40 repeats is not associated with reduced sperm motility and axonemal defects in a population of infertile males.BMC Urol. 2012 Sep 10;12:27. doi: 10.1186/1471-2490-12-27.
• [4] Sperm-associated antigens as targets for cancer immunotherapy: expression pattern and humoral immune response in cancer patients.J Immunother. 2011 Jan;34(1):28-44. doi: 10.1097/CJI.0b013e3181fb64fa.
• [5] Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging.Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):1255-1264. doi: 10.1016/j.ijrobp.2018.05.051. Epub 2018 Jun 1.
• [6] Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia.Chin J Integr Med. 2017 Sep;23(9):696-702. doi: 10.1007/s11655-015-2124-3. Epub 2015 Nov 17.
• [7] HLA class II polymorphism contributes to specify desmoglein derived peptides in pemphigus vulgaris and pemphigus foliaceus.J Autoimmun. 2000 Aug;15(1):67-73. doi: 10.1006/jaut.2000.0388.
• [8] Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis.Ann Rheum Dis. 2014 Nov;73(11):2038-46. doi: 10.1136/annrheumdis-2013-204050. Epub 2013 Aug 16.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] 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.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [18] 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.
• [19] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.