Charged multivesicular body protein 6 (CHMP6)

The protein contains 201 amino acids for an estimated molecular weight of 23485 Da.

 

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. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 34%
Model score: 0
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs61037507

The reference OMIM entry for this protein is 610901

Chmp family, member 6; chmp6
Chromatin-modifying protein 6
Charged multivesicular body protein 6
Vps20, yeast, homolog of; vps20

DESCRIPTION

CHMP6 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006).

CLONING

Using PCR, Yorikawa et al. (2005) cloned CHMP6 from a human fetus cDNA library. The deduced 201-amino acid protein contains 2 coiled-coil domains, an N-myristoylation site, and clusters of basic and acidic residues in its N- and C-terminal regions, respectively. Metabolic labeling confirmed that CHMP6 is myristoylated. Fluorescence-tagged CHMP6 localized in a punctate distribution in HeLa cells, mostly in the perinuclear area. It colocalized with an early endosomal marker and partially colocalized with a marker of both late endosomes and lysosomes.

GENE FUNCTION

By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293 cells, Yorikawa et al. (2005) showed that CHMP6 interacted with CHMP4B (610897) and EAP20 (VPS25; 610907). In vitro pull-down assays using recombinant proteins demonstrated direct physical interaction that was mediated by the N-terminal basic half of CHMP6. In transfected HeLa cells, CHMP6 colocalized with lysobisphosphatidic acid, a major phospholipid of internal vesicles of the MVB. Immunoelectron microscopy showed that CHMP6 localized in internal membranes of MVB-like structures, as well as on limiting membranes. Overexpression of CHMP6 interfered with transferrin receptor (TFRC; 190010) recycling from the plasma membrane and caused it to accumulate in the cytoplasm. Ubiquitinated proteins and endocytosed EGF (131530) also accumulated in CHMP6-expressing cells. Yorikawa et al. (2005) concluded that CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting. In S. cerevisiae, ESCRT-III consists of Vps20, Snf7 (610051), Vps24 (610052), and Vps2 (610893), which assemble in that order and require the ATPase Vps4 (see 609982) for their disassembly. Wollert et al. (2009) reconstituted and visualized by fluorescence microscopy the ESCRT-III-dependent budding and scission of intralumenal vesicles into giant unilamellar vesicles. Wollert et al. (2009) showed that 3 subunits of ESCRT-III, Vps20, Snf7, and Vps24, are sufficient to detach intralumenal vesicles. Vps2, the ESCRT-III subunit responsible for recruiting Vps4, and the ATPase activity of Vps4 were required for ESCRT-III recycling and supported additional rounds of budding. The minimum set of ESCRT-III and Vps4 proteins capable of multiple cycles of vesicle detachment corresponds to the ancient set of ESCRT proteins conserved from archaea to animals.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the CHMP6 gene to chromosome 17 (TMAP RH102270). ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 26, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610901 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed