Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKV0TIK)

• DOT Name: Adenomatous polyposis coli protein (APC)
• Synonyms: Protein APC; Deleted in polyposis 2.5
• Gene Name: APC
• Related Disease:
  Classic or attenuated familial adenomatous polyposis
  Desmoid tumour
  Familial adenomatous polyposis 1
  Gastric adenocarcinoma and proximal polyposis of the stomach
  Lung cancer
  Rectal neoplasm
  Autism
  Colorectal adenocarcinoma
  Colorectal adenoma
  Digestive system neoplasm
  Gastric neoplasm
  Glioma
  Hyperlipidemia
  Intestinal cancer
  Liver cancer
  Lung adenocarcinoma
  Lynch syndrome
  Non-small-cell lung cancer
  Ovarian cancer
  Pancreatic cancer
  Prostate neoplasm
  Rectal carcinoma
  Schizophrenia
  Brain neoplasm
  Carcinoma of esophagus
  Glioblastoma multiforme
  Hereditary diffuse gastric adenocarcinoma
  Intellectual disability
  Lung neoplasm
  Sarcoma
  Stomach cancer
  APC-related attenuated familial adenomatous polyposis
  Cenani-Lenz syndactyly syndrome
  Turcot syndrome with polyposis
  Colon adenocarcinoma
  Adult respiratory distress syndrome
  Medulloblastoma
  Mesothelioma
  Mismatch repair cancer syndrome
  Ovarian neoplasm
  Pancreatic tumour
  Thyroid gland papillary carcinoma
• UniProt ID: APC_HUMAN
• PDB ID: 1DEB; 1EMU; 1JPP; 1M5I; 1T08; 1TH1; 1V18; 2RQU; 3AU3; 3NMW; 3NMX; 3NMZ; 3QHE; 3RL7; 3RL8; 3T7U; 4G69; 4YJE; 4YJL; 4YK6; 5B6G; 5IZ6; 5IZ8; 5IZ9; 5IZA; 5Z8H; 7F6M; 7F7O; 7XTY; 8X2Q
• Pfam ID: PF05972 ; PF05956 ; PF16689 ; PF05923 ; PF18797 ; PF16634 ; PF16635 ; PF16636 ; PF16630 ; PF16633 ; PF00514 ; PF16629 ; PF05937 ; PF05924 ; PF11414
• Sequence:
  MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAM
  ASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPR
  RGFVNGSRESTGYLEELEKERSLLLADLDKEEKEKDWYYAQLQNLTKRIDSLPLTENFSL
  QTDMTRRQLEYEARQIRVAMEEQLGTCQDMEKRAQRRIARIQQIEKDILRIRQLLQSQAT
  EAERSSQNKHETGSHDAERQNEGQGVGEINMATSGNGQGSTTRMDHETASVLSSSSTHSA
  PRRLTSHLGTKVEMVYSLLSMLGTHDKDDMSRTLLAMSSSQDSCISMRQSGCLPLLIQLL
  HGNDKDSVLLGNSRGSKEARARASAALHNIIHSQPDDKRGRREIRVLHLLEQIRAYCETC
  WEWQEAHEPGMDQDKNPMPAPVEHQICPAVCVLMKLSFDEEHRHAMNELGGLQAIAELLQ
  VDCEMYGLTNDHYSITLRRYAGMALTNLTFGDVANKATLCSMKGCMRALVAQLKSESEDL
  QQVIASVLRNLSWRADVNSKKTLREVGSVKALMECALEVKKESTLKSVLSALWNLSAHCT
  ENKADICAVDGALAFLVGTLTYRSQTNTLAIIESGGGILRNVSSLIATNEDHRQILRENN
  CLQTLLQHLKSHSLTIVSNACGTLWNLSARNPKDQEALWDMGAVSMLKNLIHSKHKMIAM
  GSAAALRNLMANRPAKYKDANIMSPGSSLPSLHVRKQKALEAELDAQHLSETFDNIDNLS
  PKASHRSKQRHKQSLYGDYVFDTNRHDDNRSDNFNTGNMTVLSPYLNTTVLPSSSSSRGS
  LDSSRSEKDRSLERERGIGLGNYHPATENPGTSSKRGLQISTTAAQIAKVMEEVSAIHTS
  QEDRSSGSTTELHCVTDERNALRRSSAAHTHSNTYNFTKSENSNRTCSMPYAKLEYKRSS
  NDSLNSVSSSDGYGKRGQMKPSIESYSEDDESKFCSYGQYPADLAHKIHSANHMDDNDGE
  LDTPINYSLKYSDEQLNSGRQSPSQNERWARPKHIIEDEIKQSEQRQSRNQSTTYPVYTE
  STDDKHLKFQPHFGQQECVSPYRSRGANGSETNRVGSNHGINQNVSQSLCQEDDYEDDKP
  TNYSERYSEEEQHEEEERPTNYSIKYNEEKRHVDQPIDYSLKYATDIPSSQKQSFSFSKS
  SSGQSSKTEHMSSSSENTSTPSSNAKRQNQLHPSSAQSRSGQPQKAATCKVSSINQETIQ
  TYCVEDTPICFSRCSSLSSLSSAEDEIGCNQTTQEADSANTLQIAEIKEKIGTRSAEDPV
  SEVPAVSQHPRTKSSRLQGSSLSSESARHKAVEFSSGAKSPSKSGAQTPKSPPEHYVQET
  PLMFSRCTSVSSLDSFESRSIASSVQSEPCSGMVSGIISPSDLPDSPGQTMPPSRSKTPP
  PPPQTAQTKREVPKNKAPTAEKRESGPKQAAVNAAVQRVQVLPDADTLLHFATESTPDGF
  SCSSSLSALSLDEPFIQKDVELRIMPPVQENDNGNETESEQPKESNENQEKEAEKTIDSE
  KDLLDDSDDDDIEILEECIISAMPTKSSRKAKKPAQTASKLPPPVARKPSQLPVYKLLPS
  QNRLQPQKHVSFTPGDDMPRVYCVEGTPINFSTATSLSDLTIESPPNELAAGEGVRGGAQ
  SGEFEKRDTIPTEGRSTDEAQGGKTSSVTIPELDDNKAEEGDILAECINSAMPKGKSHKP
  FRVKKIMDQVQQASASSSAPNKNQLDGKKKKPTSPVKPIPQNTEYRTRVRKNADSKNNLN
  AERVFSDNKDSKKQNLKNNSKVFNDKLPNNEDRVRGSFAFDSPHHYTPIEGTPYCFSRND
  SLSSLDFDDDDVDLSREKAELRKAKENKESEAKVTSHTELTSNQQSANKTQAIAKQPINR
  GQPKPILQKQSTFPQSSKDIPDRGAATDEKLQNFAIENTPVCFSHNSSLSSLSDIDQENN
  NKENEPIKETEPPDSQGEPSKPQASGYAPKSFHVEDTPVCFSRNSSLSSLSIDSEDDLLQ
  ECISSAMPKKKKPSRLKGDNEKHSPRNMGGILGEDLTLDLKDIQRPDSEHGLSPDSENFD
  WKAIQEGANSIVSSLHQAAAAACLSRQASSDSDSILSLKSGISLGSPFHLTPDQEEKPFT
  SNKGPRILKPGEKSTLETKKIESESKGIKGGKKVYKSLITGKVRSNSEISGQMKQPLQAN
  MPSISRGRTMIHIPGVRNSSSSTSPVSKKGPPLKTPASKSPSEGQTATTSPRGAKPSVKS
  ELSPVARQTSQIGGSSKAPSRSGSRDSTPSRPAQQPLSRPIQSPGRNSISPGRNGISPPN
  KLSQLPRTSSPSTASTKSSGSGKMSYTSPGRQMSQQNLTKQTGLSKNASSIPRSESASKG
  LNQMNNGNGANKKVELSRMSSTKSSGSESDRSERPVLVRQSTFIKEAPSPTLRRKLEESA
  SFESLSPSSRPASPTRSQAQTPVLSPSLPDMSLSTHSSVQAGGWRKLPPNLSPTIEYNDG
  RPAKRHDIARSHSESPSRLPINRSGTWKREHSKHSSSLPRVSTWRRTGSSSSILSASSES
  SEKAKSEDEKHVNSISGTKQSKENQVSAKGTWRKIKENEFSPTNSTSQTVSSGATNGAES
  KTLIYQMAPAVSKTEDVWVRIEDCPINNPRSGRSPTGNTPPVIDSVSEKANPNIKDSKDN
  QAKQNVGNGSVPMRTVGLENRLNSFIQVDAPDQKGTEIKPGQNNPVPVSETNESSIVERT
  PFSSSSSSKHSSPSGTVAARVTPFNYNPSPRKSSADSTSARPSQIPTPVNNNTKKRDSKT
  DSTESSGTQSPKRHSGSYLVTSV
• Function: Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton. Plays a role in mediating the organization of F-actin into ordered bundles. Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.
• Tissue Specificity: Expressed in a variety of tissues: brain, small intestine, colon, thymus, skeletal muscle, heart, prostate, lung, spleen, ovary, testis kidney, placenta, blood and liver . Isoform 1A: Very strongly expressed in brain but has relatively low expression levels in other tissues . Isoform 1B: Predominant form in all tissues except for brain, including gastric mucosa and blood .
• KEGG Pathway:
  Wnt sig.ling pathway (hsa04310)
  Hippo sig.ling pathway (hsa04390)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Regulation of actin cytoskeleton (hsa04810)
  Cushing syndrome (hsa04934)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Colorectal cancer (hsa05210)
  Endometrial cancer (hsa05213)
  Basal cell carcinoma (hsa05217)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)
  Beta-catenin phosphorylation cascade (R-HSA-196299)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  Signaling by GSK3beta mutants (R-HSA-5339716)
  CTNNB1 S33 mutants aren't phosphorylated (R-HSA-5358747)
  CTNNB1 S37 mutants aren't phosphorylated (R-HSA-5358749)
  CTNNB1 S45 mutants aren't phosphorylated (R-HSA-5358751)
  CTNNB1 T41 mutants aren't phosphorylated (R-HSA-5358752)
  APC truncation mutants are not K63 polyubiquitinated (R-HSA-5467333)
  APC truncation mutants have impaired AXIN binding (R-HSA-5467337)
  AXIN missense mutants destabilize the destruction complex (R-HSA-5467340)
  Truncations of AMER1 destabilize the destruction complex (R-HSA-5467348)
  Ovarian tumor domain proteases (R-HSA-5689896)
  Apoptotic cleavage of cellular proteins (R-HSA-111465)
• BioCyc Pathway: MetaCyc:ENSG00000134982-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic or attenuated familial adenomatous polyposis	DIS99333	Definitive	Autosomal dominant	[1]
Desmoid tumour	DISGX357	Definitive	Autosomal dominant	[2]
Familial adenomatous polyposis 1	DISM44VR	Definitive	Autosomal dominant	[3]
Gastric adenocarcinoma and proximal polyposis of the stomach	DISGABXU	Definitive	Autosomal dominant	[1]
Lung cancer	DISCM4YA	Definitive	Genetic Variation	[4]
Rectal neoplasm	DISB4UZ0	Definitive	Genetic Variation	[5]
Autism	DISV4V1Z	Strong	Biomarker	[6]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[7]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[8]
Digestive system neoplasm	DISPOJCT	Strong	Biomarker	[9]
Gastric neoplasm	DISOKN4Y	Strong	Genetic Variation	[10]
Glioma	DIS5RPEH	Strong	Genetic Variation	[11]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[12]
Intestinal cancer	DISYCNF1	Strong	Genetic Variation	[13]
Liver cancer	DISDE4BI	Strong	Altered Expression	[14]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Lynch syndrome	DIS3IW5F	Strong	Genetic Variation	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[18]
Pancreatic cancer	DISJC981	Strong	Biomarker	[19]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[20]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[21]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Brain neoplasm	DISY3EKS	moderate	Genetic Variation	[23]
Carcinoma of esophagus	DISS6G4D	moderate	Biomarker	[24]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[25]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	moderate	Genetic Variation	[26]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[27]
Lung neoplasm	DISVARNB	moderate	Biomarker	[28]
Sarcoma	DISZDG3U	Moderate	Autosomal dominant	[29]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[30]
APC-related attenuated familial adenomatous polyposis	DISTNINQ	Supportive	Autosomal dominant	[31]
Cenani-Lenz syndactyly syndrome	DISHZEW1	Supportive	Autosomal recessive	[32]
Turcot syndrome with polyposis	DISDQEL1	Supportive	Autosomal dominant	[33]
Colon adenocarcinoma	DISDRE0J	Disputed	Biomarker	[34]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[35]
Medulloblastoma	DISZD2ZL	Limited	Genetic Variation	[36]
Mesothelioma	DISKWK9M	Limited	Biomarker	[37]
Mismatch repair cancer syndrome	DISIXHJ2	Limited	Genetic Variation	[38]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[18]
Pancreatic tumour	DIS3U0LK	Limited	Genetic Variation	[39]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[40]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Adenomatous polyposis coli protein (APC) affects the response to substance of Temozolomide.	[67]
DTI-015	DMXZRW0	Approved	Adenomatous polyposis coli protein (APC) affects the response to substance of DTI-015.	[67]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Adenomatous polyposis coli protein (APC).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Adenomatous polyposis coli protein (APC).	[42]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Adenomatous polyposis coli protein (APC).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Adenomatous polyposis coli protein (APC).	[44]
Marinol	DM70IK5	Approved	Marinol increases the expression of Adenomatous polyposis coli protein (APC).	[47]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Adenomatous polyposis coli protein (APC).	[48]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Adenomatous polyposis coli protein (APC).	[49]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Adenomatous polyposis coli protein (APC).	[50]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Adenomatous polyposis coli protein (APC).	[51]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Adenomatous polyposis coli protein (APC).	[52]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Adenomatous polyposis coli protein (APC).	[53]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Adenomatous polyposis coli protein (APC).	[54]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Adenomatous polyposis coli protein (APC).	[56]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Adenomatous polyposis coli protein (APC).	[42]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Adenomatous polyposis coli protein (APC).	[57]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenomatous polyposis coli protein (APC).	[60]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adenomatous polyposis coli protein (APC).	[63]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Adenomatous polyposis coli protein (APC).	[64]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Adenomatous polyposis coli protein (APC).	[44]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Adenomatous polyposis coli protein (APC).	[65]
eucalyptol	DME5CK3	Investigative	eucalyptol increases the expression of Adenomatous polyposis coli protein (APC).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Adenomatous polyposis coli protein (APC).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Adenomatous polyposis coli protein (APC).	[46]
Hydralazine	DMU8JGH	Approved	Hydralazine decreases the methylation of Adenomatous polyposis coli protein (APC).	[55]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the methylation of Adenomatous polyposis coli protein (APC).	[58]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Adenomatous polyposis coli protein (APC).	[59]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Adenomatous polyposis coli protein (APC).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adenomatous polyposis coli protein (APC).	[62]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Adenomatous polyposis coli protein (APC).	[61]

References

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