Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ZN0K3)

• DOT Name: Capping protein, Arp2/3 and myosin-I linker protein 3 (CARMIL3)
• Synonyms: Capping protein regulator and myosin 1 linker protein 3; Leucine-rich repeat-containing protein 16B
• Gene Name: CARMIL3
• Related Disease:
  Polycystic ovarian syndrome
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CARL3_HUMAN
• Pfam ID: PF17888 ; PF16000 ; PF13516
• Sequence:
  MAKPSVELTRELQDSIRRCLSQGAVLQQHHVKLETKPKKFEDRVLALTSWRLHLFLLKVP
  AKVESSFNVLEIRAFNTLSQNQILVETERGMVSMRLPSAESVDQVTRHVSSALSKVCPGP
  GCLIRRGNADTPEGPRDTSPNSETSTSTTHSVCGGFSETYAALCDYNGLHCREEVQWDVD
  TIYHAEDNREFNLLDFSHLESRDLALMVAALAYNQWFTKLYCKDLRLGSEVLEQVLHTLS
  KSGSLEELVLDNAGLKTDFVQKLAGVFGENGSCVLHALTLSHNPIEDKGFLSLSQQLLCF
  PSGLTKLCLAKTAISPRGLQALGQTFGANPAFASSLRYLDLSKNPGLLATDEANALYSFL
  AQPNALVHLDLSGTDCVIDLLLGALLHGCCSHLTYLNLARNSCSHRKGREAPPAFKQFFS
  SAYTLSHVNLSATKLPLEALRALLQGLSLNSHLSDLHLDLSSCELRSAGAQALQEQLGAV
  TCVGSLDLSDNGFDSDLLTLVPALGKNKSLKHLFLGKNFNVKAKTLEEILHKLVQLIQEE
  DCSLQSLSVADSRLKLRTSILINALGSNTCLAKVDLSGNGMEDIGAKMLSKALQINSSLR
  TILWDRNNTSALGFLDIARALESNHTLRFMSFPVSDISQAYRSAPERTEDVWQKIQWCLV
  RNNHSQTCPQEQAFRLQQGLVTSSAEQMLQRLCGRVQEEVRALRLCPLEPVQDELLYARD
  LIKDAKNSRALFPSLYELGHVLANDGPVRQRLESVASEVSKAVDKELQVILESMVSLTQE
  LCPVAMRVAEGHNKMLSNVAERVTVPRNFIRGALLEQAGQDIQNKLDEVKLSVVTYLTSS
  IVDEILQELYHSHKSLARHLTQLRTLSDPPGCPGQGQDLSSRGRGRNHDHEETTDDELGT
  NIDTMAIKKQKRCRKIRPVSAFISGSPQDMESQLGNLGIPPGWFSGLGGSQPTASGSWEG
  LSELPTHGYKLRHQTQGRPRPPRTTPPGPGRPSMPAPGTRQENGMATRLDEGLEDFFSRR
  VLEESSSYPRTLRTVRPGLSEAPLPPLQKKRRRGLFHFRRPRSFKGDRGPGSPTTGLLLP
  PPPPPPPTQESPPSPDPPSLGNNSSPCWSPEEESSLLPGFGGGRGPSFRRKMGTEGSEPG
  EGGPAPGTAQQPRVHGVALPGLERAKGWSFDGKREGPGPDQEGSTQAWQKRRSSDDAGPG
  SWKPPPPPQSTKPSFSAMRRAEATWHIAEESAPNHSCQSPSPASQDGEEEKEGTLFPERT
  LPARNAKLQDPALAPWPPKPVAVPRGRQPPQEPGVREEAEAGDAAPGVNKPRLRLSSQQD
  QEEPEVQGPPDPGRRTAPLKPKRTRRAQSCDKLEPDRRRPPDPTGTSEPGTD
• Tissue Specificity: Widely expressed, with much higher levels in fetal tissues than in adult ones. Up-regulated in certain cancer tissues.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[2]
Prostate cancer	DISF190Y	Limited	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Capping protein, Arp2/3 and myosin-I linker protein 3 (CARMIL3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Capping protein, Arp2/3 and myosin-I linker protein 3 (CARMIL3).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Capping protein, Arp2/3 and myosin-I linker protein 3 (CARMIL3).	[5]

References

• [1] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [2] Capping Protein Regulator and Myosin 1 Linker 3 Is Required for Tumor Metastasis.Mol Cancer Res. 2020 Feb;18(2):240-252. doi: 10.1158/1541-7786.MCR-19-0722. Epub 2019 Nov 6.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [5] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.