Details of Drug Off-Target (DOT)

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

• DOT Name: Major vault protein (MVP)
• Synonyms: MVP; Lung resistance-related protein
• Gene Name: MVP
• Related Disease:
  Adult glioblastoma
  Melanoma
  Wilms tumor
  Acute monocytic leukemia
  Adenocarcinoma
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Astrocytoma
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Glioma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung neoplasm
  Lymphoma
  Mitral valve prolapse
  Obesity
  Osteosarcoma
  Pancreatic cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Small-cell lung cancer
  T-cell leukaemia
  Acute lymphocytic leukaemia
  Atherosclerosis
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  High blood pressure
  Metastatic malignant neoplasm
  Epilepsy
  Focal epilepsy
  Acute myelogenous leukaemia
  Colorectal carcinoma
  Coronary heart disease
  Head-neck squamous cell carcinoma
  Neuroblastoma
  Osteoarthritis
  Type-1/2 diabetes
• UniProt ID: MVP_HUMAN
• PDB ID: 1Y7X
• Pfam ID: PF11978 ; PF01505 ; PF17794 ; PF17795 ; PF17796
• Sequence:
  MATEEFIIRIPPYHYIHVLDQNSNVSRVEVGPKTYIRQDNERVLFAPMRMVTVPPRHYCT
  VANPVSRDAQGLVLFDVTGQVRLRHADLEIRLAQDPFPLYPGEVLEKDITPLQVVLPNTA
  LHLKALLDFEDKDGDKVVAGDEWLFEGPGTYIPRKEVEVVEIIQATIIRQNQALRLRARK
  ECWDRDGKERVTGEEWLVTTVGAYLPAVFEEVLDLVDAVILTEKTALHLRARRNFRDFRG
  VSRRTGEEWLVTVQDTEAHVPDVHEEVLGVVPITTLGPHNYCVILDPVGPDGKNQLGQKR
  VVKGEKSFFLQPGEQLEQGIQDVYVLSEQQGLLLRALQPLEEGEDEEKVSHQAGDHWLIR
  GPLEYVPSAKVEVVEERQAIPLDENEGIYVQDVKTGKVRAVIGSTYMLTQDEVLWEKELP
  PGVEELLNKGQDPLADRGEKDTAKSLQPLAPRNKTRVVSYRVPHNAAVQVYDYREKRARV
  VFGPELVSLGPEEQFTVLSLSAGRPKRPHARRALCLLLGPDFFTDVITIETADHARLQLQ
  LAYNWHFEVNDRKDPQETAKLFSVPDFVGDACKAIASRVRGAVASVTFDDFHKNSARIIR
  TAVFGFETSEAKGPDGMALPRPRDQAVFPQNGLVVSSVDVQSVEPVDQRTRDALQRSVQL
  AIEITTNSQEAAAKHEAQRLEQEARGRLERQKILDQSEAEKARKELLELEALSMAVESTG
  TAKAEAESRAEAARIEGEGSVLQAKLKAQALAIETEAELQRVQKVRELELVYARAQLELE
  VSKAQQLAEVEVKKFKQMTEAIGPSTIRDLAVAGPEMQVKLLQSLGLKSTLITDGSTPIN
  LFNTAFGLLGMGPEGQPLGRRVASGPSPGEGISPQSAQAPQAPGDNHVVPVLR
• Function: Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases.
• Tissue Specificity: Present in most normal tissues. Higher expression observed in epithelial cells with secretory and excretory functions, as well as in cells chronically exposed to xenobiotics, such as bronchial cells and cells lining the intestine. Overexpressed in many multidrug-resistant cancer cells.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Wilms tumor	DISB6T16	Definitive	Altered Expression	[3]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Astrocytoma	DISL3V18	Strong	Altered Expression	[8]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[9]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Strong	Biomarker	[11]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[11]
Carcinoma	DISH9F1N	Strong	Altered Expression	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[15]
Leukemia	DISNAKFL	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[16]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Lymphoma	DISN6V4S	Strong	Altered Expression	[6]
Mitral valve prolapse	DISNCHQ3	Strong	Genetic Variation	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[9]
Pancreatic cancer	DISJC981	Strong	Biomarker	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[21]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[22]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[22]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[23]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[24]
Acute lymphocytic leukaemia	DISPX75S	moderate	Biomarker	[25]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[19]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[26]
Childhood acute lymphoblastic leukemia	DISJ5D6U	moderate	Biomarker	[25]
High blood pressure	DISY2OHH	moderate	Biomarker	[27]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[11]
Epilepsy	DISBB28L	Disputed	Genetic Variation	[28]
Focal epilepsy	DIS4LY5L	Disputed	Genetic Variation	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[30]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[31]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[32]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[20]
Osteoarthritis	DIS05URM	Limited	Biomarker	[33]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mercaptopurine	DMTM2IK	Approved	Major vault protein (MVP) decreases the response to substance of Mercaptopurine.	[64]

30 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 Major vault protein (MVP).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Major vault protein (MVP).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Major vault protein (MVP).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Major vault protein (MVP).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Major vault protein (MVP).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Major vault protein (MVP).	[40]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Major vault protein (MVP).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Major vault protein (MVP).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Major vault protein (MVP).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Major vault protein (MVP).	[45]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Major vault protein (MVP).	[45]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Major vault protein (MVP).	[46]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Major vault protein (MVP).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of Major vault protein (MVP).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Major vault protein (MVP).	[49]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Major vault protein (MVP).	[50]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Major vault protein (MVP).	[51]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Major vault protein (MVP).	[52]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Major vault protein (MVP).	[53]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Major vault protein (MVP).	[54]
CMS-024-02	DMC4X7L	Phase 3	CMS-024-02 decreases the expression of Major vault protein (MVP).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Major vault protein (MVP).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Major vault protein (MVP).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Major vault protein (MVP).	[58]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Major vault protein (MVP).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Major vault protein (MVP).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Major vault protein (MVP).	[50]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Major vault protein (MVP).	[61]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Major vault protein (MVP).	[62]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Major vault protein (MVP).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Major vault protein (MVP).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Major vault protein (MVP).	[57]

References

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