Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3X4QVX)

• DOT Name: Mucin-2 (MUC2)
• Synonyms: MUC-2; Intestinal mucin-2
• Gene Name: MUC2
• Related Disease:
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Hypertrophic cardiomyopathy
  Mucositis
  Adenocarcinoma
  Adenoma
  Breast cancer
  Cardiac failure
  Cholangiocarcinoma
  Colon carcinoma
  Colorectal adenocarcinoma
  Colorectal neoplasm
  Congestive heart failure
  Crohn disease
  Cystic fibrosis
  Escherichia coli infection
  Fetal growth restriction
  Gastric cancer
  Metastatic malignant neoplasm
  Mucinous adenocarcinoma
  Nematode infection
  Pneumonia
  Asthma
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Colitis
  Gastric neoplasm
  Inflammatory bowel disease
  Intestinal cancer
  Intrahepatic cholangiocarcinoma
  Rectal carcinoma
  Rectal neoplasm
  Stomach cancer
  Barrett esophagus
  Colonic neoplasm
  Intestinal neoplasm
  Ischemia
  Liver cirrhosis
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Ulcerative colitis
• UniProt ID: MUC2_HUMAN
• PDB ID: 6RBF; 6TM2; 6TM6; 7A5O; 7POV; 7PP6; 7PRL; 7QCL; 7QCN; 7QCU
• Pfam ID: PF08742 ; PF13330 ; PF01826 ; PF00094
• Sequence:
  MGLPLARLAAVCLALSLAGGSELQTEGRTRNHGHNVCSTWGNFHYKTFDGDVFRFPGLCD
  YNFASDCRGSYKEFAVHLKRGPGQAEAPAGVESILLTIKDDTIYLTRHLAVLNGAVVSTP
  HYSPGLLIEKSDAYTKVYSRAGLTLMWNREDALMLELDTKFRNHTCGLCGDYNGLQSYSE
  FLSDGVLFSPLEFGNMQKINQPDVVCEDPEEEVAPASCSEHRAECERLLTAEAFADCQDL
  VPLEPYLRACQQDRCRCPGGDTCVCSTVAEFSRQCSHAGGRPGNWRTATLCPKTCPGNLV
  YLESGSPCMDTCSHLEVSSLCEEHRMDGCFCPEGTVYDDIGDSGCVPVSQCHCRLHGHLY
  TPGQEITNDCEQCVCNAGRWVCKDLPCPGTCALEGGSHITTFDGKTYTFHGDCYYVLAKG
  DHNDSYALLGELAPCGSTDKQTCLKTVVLLADKKKNVVVFKSDGSVLLNELQVNLPHVTA
  SFSVFRPSSYHIMVSMAIGVRLQVQLAPVMQLFVTLDQASQGQVQGLCGNFNGLEGDDFK
  TASGLVEATGAGFANTWKAQSSCHDKLDWLDDPCSLNIESANYAEHWCSLLKKTETPFGR
  CHSAVDPAEYYKRCKYDTCNCQNNEDCLCAALSSYARACTAKGVMLWGWREHVCNKDVGS
  CPNSQVFLYNLTTCQQTCRSLSEADSHCLEGFAPVDGCGCPDHTFLDEKGRCVPLAKCSC
  YHRGLYLEAGDVVVRQEERCVCRDGRLHCRQIRLIGQSCTAPKIHMDCSNLTALATSKPR
  ALSCQTLAAGYYHTECVSGCVCPDGLMDDGRGGCVVEKECPCVHNNDLYSSGAKIKVDCN
  TCTCKRGRWVCTQAVCHGTCSIYGSGHYITFDGKYYDFDGHCSYVAVQDYCGQNSSLGSF
  SIITENVPCGTTGVTCSKAIKIFMGRTELKLEDKHRVVIQRDEGHHVAYTTREVGQYLVV
  ESSTGIIVIWDKRTTVFIKLAPSYKGTVCGLCGNFDHRSNNDFTTRDHMVVSSELDFGNS
  WKEAPTCPDVSTNPEPCSLNPHRRSWAEKQCSILKSSVFSICHSKVDPKPFYEACVHDSC
  SCDTGGDCECFCSAVASYAQECTKEGACVFWRTPDLCPIFCDYYNPPHECEWHYEPCGNR
  SFETCRTINGIHSNISVSYLEGCYPRCPKDRPIYEEDLKKCVTADKCGCYVEDTHYPPGA
  SVPTEETCKSCVCTNSSQVVCRPEEGKILNQTQDGAFCYWEICGPNGTVEKHFNICSITT
  RPSTLTTFTTITLPTTPTTFTTTTTTTTPTSSTVLSTTPKLCCLWSDWINEDHPSSGSDD
  GDRETFDGVCGAPEDIECRSVKDPHLSLEQLGQKVQCDVSVGFICKNEDQFGNGPFGLCY
  DYKIRVNCCWPMDKCITTPSPPTTTPSPPPTSTTTLPPTTTPSPPTTTTTTPPPTTTPSP
  PITTTTTPPPTTTPSPPISTTTTPPPTTTPSPPTTTPSPPTTTPSPPTTTTTTPPPTTTP
  SPPTTTPITPPASTTTLPPTTTPSPPTTTTTTPPPTTTPSPPTTTPITPPTSTTTLPPTT
  TPSPPPTTTTTPPPTTTPSPPTTTTPSPPTITTTTPPPTTTPSPPTTTTTTPPPTTTPSP
  PTTTPITPPTSTTTLPPTTTPSPPPTTTTTPPPTTTPSPPTTTTPSPPITTTTTPPPTTT
  PSSPITTTPSPPTTTMTTPSPTTTPSSPITTTTTPSSTTTPSPPPTTMTTPSPTTTPSPP
  TTTMTTLPPTTTSSPLTTTPLPPSITPPTFSPFSTTTPTTPCVPLCNWTGWLDSGKPNFH
  KPGGDTELIGDVCGPGWAANISCRATMYPDVPIGQLGQTVVCDVSVGLICKNEDQKPGGV
  IPMAFCLNYEINVQCCECVTQPTTMTTTTTENPTPTPITTTTTVTPTPTPTSTQSTTPTP
  ITTTNTVTPTPTPTGTQTPTPTPITTTTTMVTPTPTITSTQTPTPTPITTTTVTPTPTPT
  STQRTTPTSITTTTTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQTPTTTPISTTT
  MVTPTPTPTGTQTLTPTPITTTTTVTPTPTPTGTQTPTSTPISTTTTVTPTPTPTGTQTP
  TLTPITTTTTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTKSTTPTSITTTTMVTPT
  PPPTGTQTPTTTPITTTTTVTPTPTPTGTQTPTPTPITTTTTVTPTPTPTGTQTPTSTPI
  TTNTTVTPTPTPTGTPSTTLTPITTTTMVTPTPTPTGTQTPTSTPISTTTTVTPTPTPTG
  TQTPTPTPISTTTTVTPTPTPTSTQTPTTTPITTTTTVTPNPTPTGTQTPTTTPITTTTT
  VTPTPTPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTTTAITTTTTVTPTPTPTGTQTPT
  STPITTTTTVTPTPTPTGTQTPTSTPISNTTTVTPTPTPTGTQTPTVTPITTTTTVTPTR
  TPTGTKSTTPTSITTTTMVTPTPTPTGTHTPTTTPITTTTTVTPTPTPTGTQTPTPTPIT
  TTTTVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTTTPITTNTTVTPTPTPTGT
  QTPTTVLITTTTTMTPTPTPTSTKSTTVTPITTTTTVTPTPTPTGTQSTTLTPITTTTTV
  TPTPTPTGTQTPTTTPISTTTTVIPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTS
  TPISTTTTVTPTATPTGTQTPTLTPITTTTTVTSTPTPTGTQTPTPTPITTTTTVTPTPT
  PTSTQTPTSTPITTTTTVTPTPTPTGTQTPTTTHITTTTTVTPTPTPTGTQAPTPTAITT
  TTTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQSPTPTAITTTTTVTPTPTPTGTQ
  TPTTTPITTTTTVTPTPTPTGTQSTTLTPITTTTTVTPIPTPTGTQTPTSTPITTTITVT
  PTPTPTGTQTPTPTPISTTTTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQTPTTT
  PISTTTTVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTPTPITTTTTVTPTPTP
  TGTQTPTSTPITTTTTVTPTPTPTGTQTPTPTPITTTTTVTPTPTPTGTQTPTSTPITTT
  TTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQSTTLTPITTTTTVTPTPTPTGTQT
  PTSTPITTTTTVTPTPTGTQTPTPTPISTTTTVTPTPTPTGTQTPTMTPITTTTTVTPTP
  TPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTTTPIT
  TTTTVTPTPTPTGTQSTTLTPITTTTTVTPTPTPTGTQTPTPTPISTTTTVTPTPTPTGT
  QTPTTTPITTTTTVTPTPTPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTSTPITTTTTV
  TPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQAPTPTAITTTTTVTPTPTPTGTQTPTT
  TPITTTTMVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTPTPISTTTTVTPTPT
  PTGTQTPTTTPITTTTTVTPTPTPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTSTPITT
  TTTVTPTPTPTGTQTPTPTPITTTTTVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQ
  TPTTTPITTTTTVTPTPTPTGTQSTTLTPITTTTTVTPTPTPTGTQTPTSTPITTTTTVT
  PTPTPTGTQTPTPTPISTTSTVTPTPTPTGTQTPTMTPITTTTTVTPTPTPTGTQTPTST
  PITTTTTVTPTPTPTGTQTPTMTPITTTTTVTPTPTPTGTQAPTPTAITTTTTVTPTPTP
  TGTQTPTTTPITTTTTVTPTPTPTGTQSTTLTPITTTTTVTPTPTPTGTQTPTPTPISTT
  TTVTPTPTPTGTQTPTMTPITTTTTVTPTPTPTGTQTPTTTPISTTTTVTPTPTPTGTQT
  PTTTPITTTTTVTPTPTPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTTTPITTTTTVTP
  TPTPTGTQTPTTTPISTTTTVTPTPTPTGTQTPTSTPITTTTTVTPTPTPTGTQTPTTTP
  ITTTTTVTPTPTPTGTQAPTPTAITTTSTVTPTPTPTGTQTPTTTPITTTTTVTPTPTPT
  GTQSPTPTAITTTTTVTPTPTPTGTQTPTLTPITTTTTVTPTPTPTGTQTPTPTPISTTT
  TVTPTPTPTGTQTPTTTPITTTTTVTPTPTPTGTQTPTTVLITTTTTMTPTPTPTSTKST
  TVTPITTTTTVTATPTPTGTQTPTMIPISTTTTVTPTPTPTTGSTGPPTHTSTAPIAELT
  TSNPPPESSTPQTSRSTSSPLTESTTLLSTLPPAIEMTSTAPPSTPTAPTTTSGGHTLSP
  PPSTTTSPPGTPTRGTTTGSSSAPTPSTVQTTTTSAWTPTPTPLSTPSIIRTTGLRPYPS
  SVLICCVLNDTYYAPGEEVYNGTYGDTCYFVNCSLSCTLEFYNWSCPSTPSPTPTPSKST
  PTPSKPSSTPSKPTPGTKPPECPDFDPPRQENETWWLCDCFMATCKYNNTVEIVKVECEP
  PPMPTCSNGLQPVRVEDPDGCCWHWECDCYCTGWGDPHYVTFDGLYYSYQGNCTYVLVEE
  ISPSVDNFGVYIDNYHCDPNDKVSCPRTLIVRHETQEVLIKTVHMMPMQVQVQVNRQAVA
  LPYKKYGLEVYQSGINYVVDIPELGVLVSYNGLSFSVRLPYHRFGNNTKGQCGTCTNTTS
  DDCILPSGEIVSNCEAAADQWLVNDPSKPHCPHSSSTTKRPAVTVPGGGKTTPHKDCTPS
  PLCQLIKDSLFAQCHALVPPQHYYDACVFDSCFMPGSSLECASLQAYAALCAQQNICLDW
  RNHTHGACLVECPSHREYQACGPAEEPTCKSSSSQQNNTVLVEGCFCPEGTMNYAPGFDV
  CVKTCGCVGPDNVPREFGEHFEFDCKNCVCLEGGSGIICQPKRCSQKPVTHCVEDGTYLA
  TEVNPADTCCNITVCKCNTSLCKEKPSVCPLGFEVKSKMVPGRCCPFYWCESKGVCVHGN
  AEYQPGSPVYSSKCQDCVCTDKVDNNTLLNVIACTHVPCNTSCSPGFELMEAPGECCKKC
  EQTHCIIKRPDNQHVILKPGDFKSDPKNNCTFFSCVKIHNQLISSVSNITCPNFDASICI
  PGSITFMPNGCCKTCTPRNETRVPCSTVPVTTEVSYAGCTKTVLMNHCSGSCGTFVMYSA
  KAQALDHSCSCCKEEKTSQREVVLSCPNGGSLTHTYTHIESCQCQDTVCGLPTGTSRRAR
  RSPRHLGSG
• Function: Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. Major constituent of the colon mucus, which is mainly formed by large polymeric networks of MUC2 secreted by goblet cells that cover the exposed surfaces of intestine. MUC2 networks form hydrogels that guard the underlying epithelium from pathogens and other hazardous matter entering from the outside world, while permitting nutrient absorption and gas exchange. Acts as a divalent copper chaperone that protects intestinal cells from copper toxicity and facilitates nutritional copper unptake into cells. Binds both Cu(2+) and its reduced form, Cu(1+), at two juxtaposed binding sites: Cu(2+), once reduced to Cu(1+) by vitamin C (ascorbate) or other dietary antioxidants, transits to the other binding site. MUC2-bound Cu(1+) is protected from oxidation in aerobic environments, and can be released for nutritional delivery to cells. Mucin gels store antimicrobial molecules that participate in innate immunity. Mucin glycoproteins also house and feed the microbiome, lubricate tissue surfaces, and may facilitate the removal of contaminants and waste products from the body. Goblet cells synthesize two forms of MUC2 mucin that differ in branched chain O-glycosylation and the site of production in the colon: a (1) 'thick' mucus that wraps the microbiota to form fecal pellets is produced in the proximal, ascending colon. 'Thick' mucus transits along the descending colon and is lubricated by a (2) 'thin' MUC2 mucus produced in the distal colon which adheres to the 'thick' mucus.
• Tissue Specificity: Colon, small intestine, colonic tumors, bronchus, cervix and gall bladder.
• KEGG Pathway:
  Amoebiasis (hsa05146)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Defective C1GALT1C1 causes TNPS (R-HSA-5083632)
  Defective GALNT12 causes CRCS1 (R-HSA-5083636)
  Dectin-2 family (R-HSA-5621480)
  O-linked glycosylation of mucins (R-HSA-913709)
  Termination of O-glycan biosynthesis (R-HSA-977068)
  Defective GALNT3 causes HFTC (R-HSA-5083625)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Definitive	Genetic Variation	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Definitive	Genetic Variation	[1]
Hypertrophic cardiomyopathy	DISQG2AI	Definitive	Biomarker	[1]
Mucositis	DIS3FXDI	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Colorectal adenocarcinoma	DISPQOUB	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Escherichia coli infection	DISPP65M	Strong	Biomarker	[12]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[15]
Mucinous adenocarcinoma	DISKNFE8	Strong	Altered Expression	[16]
Nematode infection	DISVFLRK	Strong	Biomarker	[17]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[18]
Asthma	DISW9QNS	moderate	Biomarker	[19]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[20]
Colitis	DISAF7DD	moderate	Altered Expression	[21]
Gastric neoplasm	DISOKN4Y	moderate	Altered Expression	[22]
Inflammatory bowel disease	DISGN23E	moderate	Biomarker	[23]
Intestinal cancer	DISYCNF1	moderate	Biomarker	[24]
Intrahepatic cholangiocarcinoma	DIS6GOC8	moderate	Biomarker	[25]
Rectal carcinoma	DIS8FRR7	moderate	Biomarker	[24]
Rectal neoplasm	DISB4UZ0	moderate	Biomarker	[24]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[14]
Barrett esophagus	DIS416Y7	Limited	Altered Expression	[26]
Colonic neoplasm	DISSZ04P	Limited	Altered Expression	[27]
Intestinal neoplasm	DISK0GUH	Limited	Altered Expression	[28]
Ischemia	DIS5XOOY	Limited	Biomarker	[29]
Liver cirrhosis	DIS4G1GX	Limited	Biomarker	[30]
Pancreatic cancer	DISJC981	Limited	Posttranslational Modification	[31]
Prostate cancer	DISF190Y	Limited	Biomarker	[32]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[32]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Mucin-2 (MUC2).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mucin-2 (MUC2).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mucin-2 (MUC2).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mucin-2 (MUC2).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mucin-2 (MUC2).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Mucin-2 (MUC2).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Mucin-2 (MUC2).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Mucin-2 (MUC2).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Mucin-2 (MUC2).	[41]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Mucin-2 (MUC2).	[42]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Mucin-2 (MUC2).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mucin-2 (MUC2).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mucin-2 (MUC2).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mucin-2 (MUC2).	[47]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Mucin-2 (MUC2).	[48]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Nicotinamide-Adenine-Dinucleotide increases the expression of Mucin-2 (MUC2).	[48]
Deamido-NAD	DMDFRTI	Investigative	Deamido-NAD increases the expression of Mucin-2 (MUC2).	[48]

References

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