1. Home
  2. Targets
  3. enzyme modulator
  4. Charged multivesicular body protein 3

Tbio Charged multivesicular body protein 3

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. Selectively binds to phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other phosphoinositides tested. Involved in late stages of cytokinesis. Plays a role in endosomal sorting/trafficking of EGF receptor. Isoform 2 prevents stress-mediated cell death and accumulation of reactive oxygen species when expressed in yeast cells.

This gene encodes a protein that sorts transmembrane proteins into lysosomes/vacuoles via the multivesicular body (MVB) pathway. This protein, along with other soluble coiled-coil containing proteins, forms part of the ESCRT-III protein complex that binds to the endosomal membrane and recruits additional cofactors for protein sorting into the MVB. This protein may also co-immunoprecipitate with a member of the IFG-binding protein superfamily. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ring finger protein 103 (RNF103) gene. [provided by RefSeq, Nov 2010]

 Comments

Property Summary

NCBI Gene PubMed Count 46
Grant Count 10
Funding $1,551,346.26
PubMed Score 32.75
PubTator Score 24.61

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (9)

Disease Z-score Confidence
Brain glioma 10 3.111 1.6
Breast cancer 3,094
Multiple myeloma 1,327
atypical teratoid / rhabdoid tumor 4,369
lung adenocarcinoma 2,713
lung cancer 4,466
medulloblastoma, large-cell 6,234
osteosarcoma 7,933
ovarian cancer 8,484

Expression

  Differential Expression (8)

Disease log2 FC p
Multiple myeloma 1.007 0.006
osteosarcoma 2.180 0.000
atypical teratoid / rhabdoid tumor -1.300 0.000
medulloblastoma, large-cell -1.200 0.000
lung cancer -1.200 0.003
Breast cancer 2.700 0.043
lung adenocarcinoma -1.600 0.000
ovarian cancer -2.000 0.000

Synonym

Accession Q9Y3E7 A8K3W0 B4DG34 B8ZZM0 B8ZZX5 Q3ZTS9 Q53S71 Q53SU5 Q9NZ51
Symbols NEDF
VPS24
CGI-149

Gene

CHMP3

PANTHER Protein Class (1)

 Grant Application (10)

PDB

2GD5   2XZE   3FRT   3FRV  

 GO Function (3)

 GO Component (8)

 GO Process (19)

See all...

 Compartment GO Term (49)

See all...

 IMPC Term (2)

 MGI Term (2)

Pathway (14)

See all...

 UniProt Keyword (18)

See all...

Gene RIF (16)

PMID Text
24440309 Protein kinase CK2 alpha is involved in the phosphorylation of the ESCRT-III subunits CHMP3 and CHMP2B, as well as of VPS4B/SKD1, an ATPase that mediates ESCRT-III disassembly.
23051622 Recruitment of CHMP2A and CHMP3 by CHMP4B to HIV-1 Gag puncta is observed in in-vitro membrane model
23027949 Recruitment of CHMP2A and CHMP3 by CHMP4B to HIV-1 Gag puncta is observed in in-vitro membrane model
21827950 tight coupling of ESCRT-III CHMP3 and AMSH functions and provide insight into the regulation of ESCRT-III
20427536 Recruitment of CHMP2A and CHMP3 by CHMP4B to HIV-1 Gag puncta is observed in in-vitro membrane model
19525971 Data show that the N-terminal core domains of increased sodium tolerance-1 (IST1) and charged multivesicular body protein-3 (CHMP3) form equivalent four-helix bundles, revealing that IST1 is a previously unrecognized ESCRT-III family member.
18687924 study found the ESCRT-III proteins CHMP2A & CHMP3 could assemble in vitro into helical tubular structures that expose their membrane interaction sites on the outside of the tubule; VPS4 could bind on the inside of the tubule & disassemble the tubes
17711858 UBPY MIT domain and another ubiquitin isopeptidase, AMSH, reveals common interactions with CHMP1A and CHMP1B but a distinct selectivity of AMSH for CHMP3/VPS24, a core subunit of the ESCRT-III complex, and UBPY for CHMP7.
17686835 expression of dominant negative forms of Vps4 and Vps24, two components of the MVB pathway, rresult in an impairment in infectious herpes simplex virus assembly/egress
17331679 Data demonstrate that the VPS24 gene gives rise to two functionally distinct proteins, one of which is involved in the ESCRT pathway and another novel protein that serves an anti-apoptotic role.
More...

AA Sequence 

MGLFGKTQEKPPKELVNEWSLKIRKEMRVVDRQIRDIQREEEKVKRSVKDAAKKGQKDVCIVLAKEMIRS      1 - 70
RKAVSKLYASKAHMNSVLMGMKNQLAVLRVAGSLQKSTEVMKAMQSLVKIPEIQATMRELSKEMMKAGII     71 - 140
EEMLEDTFESMDDQEEMEEEAEMEIDRILFEITAGALGKAPSKVTDALPEPEPPGAMAASEDEEEEEEAL    141 - 210
EAMQSRLATLRS                                                              211 - 222
//

Text Mined References (55)

PMID Year Title
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
25416956 2014 A proteome-scale map of the human interactome network.
24878737 2014 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
24440309 2014 CK2 involvement in ESCRT-III complex phosphorylation.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23105106 2012 Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport.
23051622 2013 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
22660413 2012 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
21827950 2011 Structural basis for ESCRT-III CHMP3 recruitment of AMSH.
More...