Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3LGT6K)

• DOT Name: Protein jagged-1 (JAG1)
• Synonyms: Jagged1; hJ1; CD antigen CD339
• Gene Name: JAG1
• Related Disease:
  Alagille syndrome due to a JAG1 point mutation
  Alagille syndrome due to a NOTCH2 point mutation
  Acute myelogenous leukaemia
  Adenocarcinoma
  Aorta coarctation
  Artery stenosis
  Asthma
  Bone disease
  Bone osteosarcoma
  Cervical cancer
  Cervical carcinoma
  Charcot-Marie-Tooth disease, axonal, Type 2HH
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Glioma
  High blood pressure
  Liver cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Osteoarthritis
  Osteosarcoma
  Ovarian cancer
  Plasma cell myeloma
  Schizophrenia
  Stomach cancer
  Type-1/2 diabetes
  Adult glioblastoma
  Breast neoplasm
  Glioblastoma multiforme
  Tetralogy of fallot
  Cataract
  Metastatic malignant neoplasm
  Moyamoya disease
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: JAG1_HUMAN
• PDB ID: 2KB9; 2VJ2; 4CBZ; 4CC0; 4CC1; 4XI7; 5BO1
• Pfam ID: PF21700 ; PF01414 ; PF00008 ; PF07645 ; PF12661 ; PF07657
• Sequence:
  MRSPRTRGRSGRPLSLLLALLCALRAKVCGASGQFELEILSMQNVNGELQNGNCCGGARN
  PGDRKCTRDECDTYFKVCLKEYQSRVTAGGPCSFGSGSTPVIGGNTFNLKASRGNDRNRI
  VLPFSFAWPRSYTLLVEAWDSSNDTVQPDSIIEKASHSGMINPSRQWQTLKQNTGVAHFE
  YQIRVTCDDYYYGFGCNKFCRPRDDFFGHYACDQNGNKTCMEGWMGPECNRAICRQGCSP
  KHGSCKLPGDCRCQYGWQGLYCDKCIPHPGCVHGICNEPWQCLCETNWGGQLCDKDLNYC
  GTHQPCLNGGTCSNTGPDKYQCSCPEGYSGPNCEIAEHACLSDPCHNRGSCKETSLGFEC
  ECSPGWTGPTCSTNIDDCSPNNCSHGGTCQDLVNGFKCVCPPQWTGKTCQLDANECEAKP
  CVNAKSCKNLIASYYCDCLPGWMGQNCDININDCLGQCQNDASCRDLVNGYRCICPPGYA
  GDHCERDIDECASNPCLNGGHCQNEINRFQCLCPTGFSGNLCQLDIDYCEPNPCQNGAQC
  YNRASDYFCKCPEDYEGKNCSHLKDHCRTTPCEVIDSCTVAMASNDTPEGVRYISSNVCG
  PHGKCKSQSGGKFTCDCNKGFTGTYCHENINDCESNPCRNGGTCIDGVNSYKCICSDGWE
  GAYCETNINDCSQNPCHNGGTCRDLVNDFYCDCKNGWKGKTCHSRDSQCDEATCNNGGTC
  YDEGDAFKCMCPGGWEGTTCNIARNSSCLPNPCHNGGTCVVNGESFTCVCKEGWEGPICA
  QNTNDCSPHPCYNSGTCVDGDNWYRCECAPGFAGPDCRININECQSSPCAFGATCVDEIN
  GYRCVCPPGHSGAKCQEVSGRPCITMGSVIPDGAKWDDDCNTCQCLNGRIACSKVWCGPR
  PCLLHKGHSECPSGQSCIPILDDQCFVHPCTGVGECRSSSLQPVKTKCTSDSYYQDNCAN
  ITFTFNKEMMSPGLTTEHICSELRNLNILKNVSAEYSIYIACEPSPSANNEIHVAISAED
  IRDDGNPIKEITDKIIDLVSKRDGNSSLIAAVAEVRVQRRPLKNRTDFLVPLLSSVLTVA
  WICCLVTAFYWCLRKRRKPGSHTHSASEDNTTNNVREQLNQIKNPIEKHGANTVPIKDYE
  NKNSKMSKIRTHNSEVEEDDMDKHQQKARFAKQPAYTLVDREEKPPNGTPTKHPNWTNKQ
  DNRDLESAQSLNRMEYIV
• Function: Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation. Enhances fibroblast growth factor-induced angiogenesis (in vitro).
• Tissue Specificity: Widely expressed in adult and fetal tissues. In cervix epithelium expressed in undifferentiated subcolumnar reserve cells and squamous metaplasia. Expression is up-regulated in cervical squamous cell carcinoma. Expressed in bone marrow cell line HS-27a which supports the long-term maintenance of immature progenitor cells.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  Notch sig.ling pathway (hsa04330)
  Apelin sig.ling pathway (hsa04371)
  Th1 and Th2 cell differentiation (hsa04658)
  TNF sig.ling pathway (hsa04668)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Breast cancer (hsa05224)
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 t(7 (R-HSA-2660826)
  Constitutive Signaling by NOTCH1 HD Domain Mutants (R-HSA-2691232)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096)
  RUNX3 regulates NOTCH signaling (R-HSA-8941856)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC3 GTPase cycle (R-HSA-9013423)
  NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507)
  NOTCH4 Activation and Transmission of Signal to the Nucleus (R-HSA-9013700)
  M1580_K2555) Translocation Mutant (9)(NOTCH1)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alagille syndrome due to a JAG1 point mutation	DISNUZCL	Definitive	Autosomal dominant	[1]
Alagille syndrome due to a NOTCH2 point mutation	DISZGPUX	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Aorta coarctation	DISAFXDJ	Strong	Altered Expression	[5]
Artery stenosis	DISQU4Q5	Strong	Genetic Variation	[6]
Asthma	DISW9QNS	Strong	Biomarker	[7]
Bone disease	DISE1F82	Strong	Altered Expression	[8]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Charcot-Marie-Tooth disease, axonal, Type 2HH	DISWZXRQ	Strong	Autosomal dominant	[11]
Colon adenocarcinoma	DISDRE0J	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Altered Expression	[13]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Biomarker	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
High blood pressure	DISY2OHH	Strong	Biomarker	[18]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[19]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[19]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[19]
Lung neoplasm	DISVARNB	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[9]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[22]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[23]
Stomach cancer	DISKIJSX	Strong	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[24]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[25]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[26]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[25]
Tetralogy of fallot	DISMHFNW	Supportive	Autosomal dominant	[27]
Cataract	DISUD7SL	Limited	Biomarker	[28]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[29]
Moyamoya disease	DISO62CA	Limited	Biomarker	[30]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[15]
Prostate cancer	DISF190Y	Limited	Biomarker	[31]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein jagged-1 (JAG1).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein jagged-1 (JAG1).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein jagged-1 (JAG1).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein jagged-1 (JAG1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein jagged-1 (JAG1).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein jagged-1 (JAG1).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein jagged-1 (JAG1).	[38]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein jagged-1 (JAG1).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein jagged-1 (JAG1).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein jagged-1 (JAG1).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein jagged-1 (JAG1).	[42]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein jagged-1 (JAG1).	[43]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein jagged-1 (JAG1).	[44]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein jagged-1 (JAG1).	[45]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein jagged-1 (JAG1).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein jagged-1 (JAG1).	[46]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein jagged-1 (JAG1).	[47]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Protein jagged-1 (JAG1).	[48]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Protein jagged-1 (JAG1).	[49]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Protein jagged-1 (JAG1).	[50]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Protein jagged-1 (JAG1).	[51]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Protein jagged-1 (JAG1).	[52]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Protein jagged-1 (JAG1).	[53]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein jagged-1 (JAG1).	[54]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Protein jagged-1 (JAG1).	[55]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Protein jagged-1 (JAG1).	[56]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Protein jagged-1 (JAG1).	[57]
Glycyrrhizin	DM8M2N3	Phase 3	Glycyrrhizin decreases the expression of Protein jagged-1 (JAG1).	[58]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Protein jagged-1 (JAG1).	[59]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein jagged-1 (JAG1).	[60]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein jagged-1 (JAG1).	[61]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein jagged-1 (JAG1).	[62]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Protein jagged-1 (JAG1).	[64]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein jagged-1 (JAG1).	[65]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein jagged-1 (JAG1).	[66]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein jagged-1 (JAG1).	[67]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein jagged-1 (JAG1).	[68]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein jagged-1 (JAG1).	[69]
Paraquat	DMR8O3X	Investigative	Paraquat affects the expression of Protein jagged-1 (JAG1).	[70]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Protein jagged-1 (JAG1).	[71]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Protein jagged-1 (JAG1).	[72]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Protein jagged-1 (JAG1).	[73]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Protein jagged-1 (JAG1).	[74]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone decreases the expression of Protein jagged-1 (JAG1).	[47]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Protein jagged-1 (JAG1).	[75]
9-phenanthrol	DMJFBQ1	Investigative	9-phenanthrol decreases the expression of Protein jagged-1 (JAG1).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein jagged-1 (JAG1).	[63]

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