Details of Drug Off-Target (DOT)

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

• DOT Name: Sperm-associated microtubule inner protein 4 (SPMIP4)
• Gene Name: SPMIP4
• UniProt ID: SMIP4_HUMAN
• Pfam ID: PF15093
• Sequence:
  MEVIHGRPYCCRELEGADILSNTFYSNELHNPLQTVTRPTASEDRYQELRESLQQCRLPW
  GAEREYGGIIPISLPEDHRPKYEPPRVMGKGHQHYGFGGETWPRKLPVEQFYYLTQNKKS
  DVYGNDSLIPKPPNSTVGEICLPYPIEHPYHTHICRGAMFPTFTSPEDLYTGIKARTQQP
  FPPTVPTKAYDSTVLKTRGNPYRYELIDIPMDSKKKALTWPGQGVYYDFPRGVEKNKPVF
  YPKPPKTFAPNTSLNSWDPICSAKEANIQRNLERSHWLTSYTHDFTGLGPMDPLELDDYH
  EKMVAELTRKIGFDPEPQEKFHPVFKPPRPLEGRIARLIQNRRSLEAIVQQRPRSCPDCT
  PRVLCNFHTFVPSSKEMVALSDNIPAGVTHKNQDIEEKIIEEQSLLSTYELPSCYPTKDL
  TSIYDIKPFPKITDTKKTEDLYWRQQSLKTQPTPYCKPDHWIHYENLKSPLRDQYNMCPD
  PVSLSKPSVLQNKQDTEAFTLEHFLSKPEEELFLNMENNEETRPVLGWIPRAGVTKPQTN
  LLELKNSFSKTGAQKRFHKSILEDHKDLRDNEHSGMKHQFYGHNSYYFYN
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella.
• Tissue Specificity: Predominantly expressed in the testes.

Molecular Interaction Atlas (MIA) of This DOT

7 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 Sperm-associated microtubule inner protein 4 (SPMIP4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sperm-associated microtubule inner protein 4 (SPMIP4).	[8]

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 affects the methylation of Sperm-associated microtubule inner protein 4 (SPMIP4).	[6]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] 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.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.