Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TUF6K)

• DOT Name: Cation channel sperm-associated targeting subunit tau (C2CD6)
• Synonyms: CatSper-tau; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 11 protein; C2 calcium-dependent domain-containing protein 6
• Gene Name: C2CD6
• Related Disease: Breast carcinoma
• UniProt ID: CTSRT_HUMAN
• Pfam ID: PF15729
• Sequence:
  MEPPQETNRPFSTLDNRSGQVQVLSATPLLQRNPYSSPDIMHIKGSEASSVPYALNQGTT
  ALPKNKNQEGTGHRLLNMLRKTLKESDSEELEITQETPNLVPFGDVVGCLGIHIKNCRHF
  MPKISLQHYANLFIRISINKAVKCTKMCSLLSKNDEKNTVIKFDEVKYFSVQVPRRYDDK
  RNNILLELIQYDNREKRAFLLGSVQIHLYEVIQKGCFIEEVQVLHGNIFVCRLEVEFMFS
  YGNFGYGFSHQLKPLQKITEPSMFMNLAPPPERTDPVTKVITPQTVEYPAFLSPDLNVTV
  GTPAVQSSNQPSVVRLEKLQQQPRERLEKMKKEYRNLNTWIDKANYLESILMPKLEHKDS
  EETNIDEASENTKSNHPEEELENIVGVDIPLVNEEAETTANELLDNDSEKGLTIPTLNQS
  DQDNSTADASKNDESTPSPTEVHSLCTISNQETIKAGRIPPLGERQSESMPDRKMKNVFF
  PLEVKLKDNYPSILKADSSLSEVAFSPKEYNSPSFRPEYIEFKPKFQFQKFNKNGFDPFL
  RNINKMSVRKRKDQDIYKYRNILGAEVIEHEDQDPPYPAQSKTAGPANTTWAHDPNIFTT
  KMLETENKLAPDPTINTIKGLDTKNSLKENLPNVSLPSIKGESSRAGNVQANTCHLSKSL
  NFTPHIEYLKQSMILKSILSENLQDLSDKLFSKPEVSMNSEAREKSSSPLLSIHDKSSSS
  MEDNVLEKKQDLNNWLSEKDILNSKTTLSQIIKNIPADSFSEGSQIIENIPADSLLEGGQ
  VIKNIPEYSLSEGGQIIKNIPADSFLESGPGQSPEVEEHVSKKHFEADERDFPIKKNSST
  KKKHLISEVPNSKSGSSGTVHDYIMRQIFTAPIFSELEIEVKEPSETPMNLENQLPTPWK
  RSLSSHILFHEENADEIELPQPRSATSQIIQAFPIDTLLESGIIKVIELDKEHHKSSLLG
  TGITSPKGNLKDSQEYYSEIRSETEPLSEQSIPIIPKDTTSVSRAEFIQEDQNMFPQDSS
  YYSIANKELYLPRNGQRLCKDKNDLSSTLESLTNSLMDKLSESDEIMLKSFLKNIFNVFF
  KYNHSERRGQPEKELERLIQPSFTSDTEHLEELQEDFDKADKLDRKPILSPKLRVFLEEL
  SESEVKHLKSELSKQIQHYLVERLSESGHITKEDLPKIYQNLYLMNEKAEQKGPNSFQGK
  YSETVKEIMSFVNNFNHHFIDKHLEIKLRSFLKEILQNYFLKNISESSLFNETASETIYP
  NISSLRTKSVSISFHELEQDISKGSFGRRFEINMKYPLSKSLQNYLIALSENELLHLKAD
  LSKHLQSLFIEKLSKSGLMTKKQLEGINQHINLLNSSSIPLKYIKTHLPFRDDCHFVEKH
  SEKQNKYSRIVQQTTLQTVSEDKLREAELIREKEKKYFPLQNLKGNSSLIKEQKSYYTKE
  EAKTPSLIKVQPSSNENIQASPLSKSSEILTDILLKKLRKEHVFTQLPQAENSVHKTEIQ
  DPYSWGGKSKITQSKAWCEKTLKMKSLDRKEHVNIYKWTVQEKPEAVLTSYPRIPNARMP
  REDEYLNRITFPSWQSSTLTHFNTETGEKSKLEDQYCQTLKGNNNNNKKHLVTFAQYKKE
  IQTLYIKPDEICSEKCAKFPEIQSFQYKVVEDEKNLKPHLFPELFKIEDLKPKVRKERDR
  VAQPKKSFNKIVRILPTTLPTTRIHLKKSVPRTLLHWTARRTIHDCSDKFEDLHDMTSFT
  HLKKVKSRSRLLGKSSDDIHNHARHSARPYTAPEVNKQRESYSGKFTSRRMVSSGLVHIN
  DKTSDYEMHKMRPKKIKRGY
• 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. Required for CatSper complex targeting and trafficking into the quadrilinear nanodomains. Targets the preassembled CatSper complexes to elongating flagella, where it links the channel-carrying vesicles and motor proteins.
• Tissue Specificity: Expressed in testis (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cation channel sperm-associated targeting subunit tau (C2CD6).	[2]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Cation channel sperm-associated targeting subunit tau (C2CD6).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cation channel sperm-associated targeting subunit tau (C2CD6).	[5]

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 Cation channel sperm-associated targeting subunit tau (C2CD6).	[4]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] 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.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] 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.
• [5] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.