Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ0WQL2)

• DOT Name: Cation channel sperm-associated auxiliary subunit beta (CATSPERB)
• Synonyms: CatSper-beta
• Gene Name: CATSPERB
• Related Disease: Venous thromboembolism
• UniProt ID: CTSRB_HUMAN
• Pfam ID: PF15149 ; PF21541 ; PF21548
• Sequence:
  MESPLIYVSVLLLNIFEFSSGIVYNKDDTEKRFACSNKGFPQENEIIKLYLFLENLKIQC
  FFQTENEIASKAMLSVFTSGGLAPSLGIMNSTYNGIFHFNLTLFSDRILWLVDIPRENIT
  QSTDIAAVEEWLVRITLHHGLNIYATEGTLLDVIREPILQWTPGDVIPESEISKLYPHVV
  DLKVTKCPCANDVALLGFIVDTIVDGVYIGITFGGFWHDYDTTWFNMTQTIYSQLQEEYE
  DLSLVDMVLTNHFLVILTSLGLFVSEDLRYPSRHSLSFSRADFCGFERVDYVKGKLWYNE
  RCFANREHFEVDYVTVTFERNRTLSESSSCFYSQEPFLEWVPCLPHIFKGIKIFPTVLTF
  LVDQERGTGVYLFYNKVRKTAIASVSTLRNNEPNSQSKFPIFRFPSSFSSPVGMVFHPRS
  HFLYAYGNQIWLSVDGGNTFQLIANFHDDIIKKTFHSFYTSAITFVSQRGKVYSTKAGMG
  RYSAVGSVTERIFTLYYDHLGFLHKLTLGRFEASGPPTAFGNSRNLFGQPPDMGFETALA
  PQHTSLDEIIFFAYVPENEPQETIYSKKFGNIHYGKVIHSGKTGRAYIRKVLQHTTPKGF
  LSSVIAEMKEPFGLEEVNESSCLSSSLLINKAGNVYKLTLDSQVVQALFEDTDIEKTVVL
  PGYSSFLITSILDNKNALAIATMPESAPNNMTFLKSTWFLYNFGQRNGRTWKIYSKPCNY
  WFQHDDSPSLNIVKYIDLGNSYVLKAKVIRNAKGFRMLEIPLLTVFVGNPNLLEVTAEVT
  FDDTDSYVITISAASKVLHQGSTSLAFIMWSASTECFVTTMVPTLKSSCSYLRSMHHIPS
  KFIPFEDWISGVHKDSQGFNLIKTLPINYRPPSNMGIAIPLTDNFYHADPSKPIPRNMFH
  MSKKTGKFKQCANVSTREECNCTKDQKFSHAVAFSDCREKVPRFKFPITQYPVSLEIINE
  DGRVPLQSPYLVTVTEVNMRHNWKLKHTVPENIKRMKQLVEPILGAAVYNPSGLNLSIKG
  SELFHFRVTVISGVTFCNLIEEFQIYVDEAPLPFPGHTLIAVATAVVLGGLIFIAFMFQL
  QGIHPWRTFQRWIRRNQEKFSSISLSELIHRSKSEE
• Function: Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization.
• Reactome Pathway: Sperm Motility And Taxes (R-HSA-1300642)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cation channel sperm-associated auxiliary subunit beta (CATSPERB).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cation channel sperm-associated auxiliary subunit beta (CATSPERB).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cation channel sperm-associated auxiliary subunit beta (CATSPERB).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cation channel sperm-associated auxiliary subunit beta (CATSPERB).	[4]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cation channel sperm-associated auxiliary subunit beta (CATSPERB).	[5]

References

• [1] Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.Nat Genet. 2019 Nov;51(11):1574-1579. doi: 10.1038/s41588-019-0519-3. Epub 2019 Nov 1.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [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.