Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZA7RJB)

DOT Name Charged multivesicular body protein 2b (CHMP2B)
Synonyms CHMP2.5; Chromatin-modifying protein 2b; CHMP2b; Vacuolar protein sorting-associated protein 2-2; Vps2-2; hVps2-2
Gene Name CHMP2B
Related Disease
Familial hypocalciuric hypercalcemia 1 ( )
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 ( )
Alzheimer disease ( )
Amyloidosis ( )
Amyotrophic lateral sclerosis type 1 ( )
Amyotrophic lateral sclerosis-parkinsonism-dementia complex ( )
Anemia, hypochromic microcytic with iron overload ( )
Coeliac disease ( )
Congenital diaphragmatic hernia ( )
Dystonia ( )
Epithelial ovarian cancer ( )
Frontotemporal dementia ( )
Hepatocellular carcinoma ( )
Hereditary hemochromatosis ( )
Hyperglycemia ( )
Inflammatory bowel disease ( )
Iron-deficiency anemia ( )
Kidney cancer ( )
Motor neurone disease ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Parkinsonian disorder ( )
Pick disease ( )
Renal carcinoma ( )
Semantic dementia ( )
Triple negative breast cancer ( )
Ulcerative colitis ( )
Wilson disease ( )
Adrenoleukodystrophy ( )
Age-related macular degeneration ( )
Anemia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Behavioral variant of frontotemporal dementia ( )
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 ( )
Nephropathy ( )
Obsolete amyotrophic lateral sclerosis type 17 ( )
Progressive non-fluent aphasia ( )
Retinopathy ( )
Stroke ( )
Type-1/2 diabetes ( )
Amyotrophic lateral sclerosis ( )
Hypochromic microcytic anemia ( )
Dementia ( )
Intellectual disability ( )
Lewy body dementia ( )
Thalassemia ( )
Tuberculosis ( )
UniProt ID
CHM2B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2JQK
Pfam ID
PF03357
Sequence
MASLFKKKTVDDVIKEQNRELRGTQRAIIRDRAALEKQEKQLELEIKKMAKIGNKEACKV
LAKQLVHLRKQKTRTFAVSSKVTSMSTQTKVMNSQMKMAGAMSTTAKTMQAVNKKMDPQK
TLQTMQNFQKENMKMEMTEEMINDTLDDIFDGSDDEEESQDIVNQVLDEIGIEISGKMAK
APSAARSLPSASTSKATISDEEIERQLKALGVD
Function
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.
Tissue Specificity
Widely expressed. Expressed in brain, heart, skeletal muscle, spleen, kidney, liver, small intestine, pancreas, lung, placenta and leukocytes. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal chord, occipital lobe, frontal lobe, temporal lobe and putamen.
KEGG Pathway
Endocytosis (hsa04144 )
Necroptosis (hsa04217 )
Amyotrophic lateral sclerosis (hsa05014 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Reactome Pathway
Macroautophagy (R-HSA-1632852 )
Pyroptosis (R-HSA-5620971 )
Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729 )
HCMV Late Events (R-HSA-9610379 )
Late endosomal microautophagy (R-HSA-9615710 )
Sealing of the nuclear envelope (NE) by ESCRT-III (R-HSA-9668328 )
Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9679504 )
Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9694676 )
Budding and maturation of HIV virion (R-HSA-162588 )

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Familial hypocalciuric hypercalcemia 1 DISPW6O5 Definitive Altered Expression [1]
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 DISDD18L Definitive Autosomal dominant [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Amyloidosis DISHTAI2 Strong Biomarker [4]
Amyotrophic lateral sclerosis type 1 DIS5A2M0 Strong Biomarker [5]
Amyotrophic lateral sclerosis-parkinsonism-dementia complex DISTHQI1 Strong Biomarker [6]
Anemia, hypochromic microcytic with iron overload DIST0BXW Strong Genetic Variation [7]
Coeliac disease DISIY60C Strong Genetic Variation [8]
Congenital diaphragmatic hernia DIS0IPVU Strong Biomarker [9]
Dystonia DISJLFGW Strong Biomarker [10]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [11]
Frontotemporal dementia DISKYHXL Strong Genetic Variation [12]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [13]
Hereditary hemochromatosis DISVG5MT Strong Biomarker [14]
Hyperglycemia DIS0BZB5 Strong Altered Expression [15]
Inflammatory bowel disease DISGN23E Strong Biomarker [16]
Iron-deficiency anemia DIS0VQYF Strong Biomarker [14]
Kidney cancer DISBIPKM Strong Altered Expression [17]
Motor neurone disease DISUHWUI Strong Genetic Variation [18]
Neoplasm DISZKGEW Strong Biomarker [13]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Ovarian cancer DISZJHAP Strong Biomarker [11]
Ovarian neoplasm DISEAFTY Strong Biomarker [11]
Parkinson disease DISQVHKL Strong Genetic Variation [20]
Parkinsonian disorder DISHGY45 Strong Genetic Variation [21]
Pick disease DISP6X50 Strong Biomarker [22]
Renal carcinoma DISER9XT Strong Altered Expression [17]
Semantic dementia DISA7775 Strong SusceptibilityMutation [23]
Triple negative breast cancer DISAMG6N Strong Altered Expression [24]
Ulcerative colitis DIS8K27O Strong Altered Expression [25]
Wilson disease DISVS9H7 Strong Genetic Variation [26]
Adrenoleukodystrophy DISTUD1F moderate Altered Expression [27]
Age-related macular degeneration DIS0XS2C moderate Genetic Variation [28]
Anemia DISTVL0C moderate Genetic Variation [8]
Arteriosclerosis DISK5QGC moderate Biomarker [29]
Atherosclerosis DISMN9J3 moderate Biomarker [29]
Behavioral variant of frontotemporal dementia DISQHX2V moderate SusceptibilityMutation [23]
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 DIS8SB8X moderate Biomarker [10]
Nephropathy DISXWP4P moderate Biomarker [29]
Obsolete amyotrophic lateral sclerosis type 17 DISDGTDX Moderate Autosomal dominant [30]
Progressive non-fluent aphasia DIS9HZET moderate SusceptibilityMutation [23]
Retinopathy DISB4B0F moderate Biomarker [29]
Stroke DISX6UHX moderate Altered Expression [31]
Type-1/2 diabetes DISIUHAP moderate Genetic Variation [29]
Amyotrophic lateral sclerosis DISF7HVM Supportive Autosomal dominant [32]
Hypochromic microcytic anemia DIS0RMTQ Disputed Genetic Variation [33]
Dementia DISXL1WY Limited Genetic Variation [34]
Intellectual disability DISMBNXP Limited Genetic Variation [35]
Lewy body dementia DISAE66J Limited Biomarker [36]
Thalassemia DIS76XZB Limited Biomarker [37]
Tuberculosis DIS2YIMD Limited Genetic Variation [38]
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⏷ Show the Full List of 51 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Charged multivesicular body protein 2b (CHMP2B). [39]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Charged multivesicular body protein 2b (CHMP2B). [40]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Charged multivesicular body protein 2b (CHMP2B). [41]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Charged multivesicular body protein 2b (CHMP2B). [42]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Charged multivesicular body protein 2b (CHMP2B). [43]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Charged multivesicular body protein 2b (CHMP2B). [44]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Charged multivesicular body protein 2b (CHMP2B). [45]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Charged multivesicular body protein 2b (CHMP2B). [46]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Charged multivesicular body protein 2b (CHMP2B). [49]
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⏷ Show the Full List of 9 Drug(s)
2 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 decreases the phosphorylation of Charged multivesicular body protein 2b (CHMP2B). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Charged multivesicular body protein 2b (CHMP2B). [48]
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References

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23 Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review.Transl Neurodegener. 2013 Apr 19;2(1):8. doi: 10.1186/2047-9158-2-8.
24 Deferoxamine-inducedhigh expression of TfR1 and DMT1 enhanced iron uptake intriple-negative breast cancer cells by activatingIL-6/PI3K/AKTpathway.Onco Targets Ther. 2019 May 31;12:4359-4377. doi: 10.2147/OTT.S193507. eCollection 2019.
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32 Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS One. 2010 Mar 24;5(3):e9872. doi: 10.1371/journal.pone.0009872.
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