Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0VHIYZ)

• DOT Name: Disheveled-associated activator of morphogenesis 1 (DAAM1)
• Gene Name: DAAM1
• Related Disease:
  Diabetic kidney disease
  Epithelial ovarian cancer
  Essential thrombocythemia
  Lung cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Thrombocytosis disease
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Gastrointestinal stromal tumour
  Urinary bladder cancer
  Adult glioblastoma
  Glioblastoma multiforme
  Pneumocystis pneumonia
• UniProt ID: DAAM1_HUMAN
• PDB ID: 2J1D; 2Z6E
• Pfam ID: PF06367 ; PF06371 ; PF02181
• Sequence:
  MAPRKRGGRGISFIFCCFRNNDHPEITYRLRNDSNFALQTMEPALPMPPVEELDVMFSEL
  VDELDLTDKHREAMFALPAEKKWQIYCSKKKDQEENKGATSWPEFYIDQLNSMAARKSLL
  ALEKEEEEERSKTIESLKTALRTKPMRFVTRFIDLDGLSCILNFLKTMDYETSESRIHTS
  LIGCIKALMNNSQGRAHVLAHSESINVIAQSLSTENIKTKVAVLEILGAVCLVPGGHKKV
  LQAMLHYQKYASERTRFQTLINDLDKSTGRYRDEVSLKTAIMSFINAVLSQGAGVESLDF
  RLHLRYEFLMLGIQPVIDKLREHENSTLDRHLDFFEMLRNEDELEFAKRFELVHIDTKSA
  TQMFELTRKRLTHSEAYPHFMSILHHCLQMPYKRSGNTVQYWLLLDRIIQQIVIQNDKGQ
  DPDSTPLENFNIKNVVRMLVNENEVKQWKEQAEKMRKEHNELQQKLEKKERECDAKTQEK
  EEMMQTLNKMKEKLEKETTEHKQVKQQVADLTAQLHELSRRAVCASIPGGPSPGAPGGPF
  PSSVPGSLLPPPPPPPLPGGMLPPPPPPLPPGGPPPPPGPPPLGAIMPPPGAPMGLALKK
  KSIPQPTNALKSFNWSKLPENKLEGTVWTEIDDTKVFKILDLEDLERTFSAYQRQQDFFV
  NSNSKQKEADAIDDTLSSKLKVKELSVIDGRRAQNCNILLSRLKLSNDEIKRAILTMDEQ
  EDLPKDMLEQLLKFVPEKSDIDLLEEHKHELDRMAKADRFLFEMSRINHYQQRLQSLYFK
  KKFAERVAEVKPKVEAIRSGSEEVFRSGALKQLLEVVLAFGNYMNKGQRGNAYGFKISSL
  NKIADTKSSIDKNITLLHYLITIVENKYPSVLNLNEELRDIPQAAKVNMTELDKEISTLR
  SGLKAVETELEYQKSQPPQPGDKFVSVVSQFITVASFSFSDVEDLLAEAKDLFTKAVKHF
  GEEAGKIQPDEFFGIFDQFLQAVSEAKQENENMRKKKEEEERRARMEAQLKEQRERERKM
  RKAKENSEESGEFDDLVSALRSGEVFDKDLSKLKRNRKRITNQMTDSSRERPITKLNF
• Function: Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation. May play a role as a scaffolding protein to recruit Rho-GDP and Rho-GEF, thereby enhancing Rho-GTP formation. Can direct nucleation and elongation of new actin filaments. Involved in building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Together with DAAM2, required for myocardial maturation and sarcomere assembly.
• Tissue Specificity: Expressed in all tissues examined.
• KEGG Pathway:
  Wnt sig.ling pathway (hsa04310)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  RHO GTPases Activate Formins (R-HSA-5663220)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  PCP/CE pathway (R-HSA-4086400)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Essential thrombocythemia	DISWWK11	Strong	Altered Expression	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[2]
Thrombocytosis disease	DISNG0P4	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[6]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[6]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[7]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[8]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[9]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[10]

19 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 Disheveled-associated activator of morphogenesis 1 (DAAM1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[16]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[13]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[28]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[29]

3 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 Disheveled-associated activator of morphogenesis 1 (DAAM1).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Disheveled-associated activator of morphogenesis 1 (DAAM1).	[25]

References

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• [3] Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.Blood. 2012 Oct 25;120(17):3575-85. doi: 10.1182/blood-2012-02-411264. Epub 2012 Aug 6.
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• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
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• [22] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [23] 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.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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