Charged multivesicular body protein 2a (CHMP2A)

The protein contains 222 amino acids for an estimated molecular weight of 25104 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 (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.', '(Microbial infection) The ESCRT machinery functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Involved in HIV-1 p6- and p9-dependent virus release. (updated: Oct. 25, 2017)

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.

Interpro domains
Total structural coverage: 24%
Model score: 34

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The reference OMIM entry for this protein is 610893

Chmp family, member 2a; chmp2a
Chromatin-modifying protein 2a
Charged multivesicular body protein 2a
Vacuolar protein sorting 2, yeast, homolog of, a; vps2a
Vps2
Bc2

DESCRIPTION

CHMP2A 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

By yeast 2-hybrid screening using mouse Skd1 (VPS4B; 609983) as bait, Fujita et al. (2004) cloned mouse Chmp2a, which they called Vps2. They identified human CHMP2A by database analysis. The deduced 222-amino acid mouse protein contains N- and C-terminal coiled-coil regions. Northern blot analysis detected Chmp2a expression in most mouse tissues examined, with highest levels in heart, brain, liver, and kidney. Immunofluorescence microscopy localized Chmp1a mainly to the cytoplasm.

GENE FUNCTION

Fujita et al. (2004) found that deletion of the N-terminal coiled-coil domain of mouse Chmp2a caused Chmp2a to localize mainly to the nucleus rather than the cytoplasm. Pull-down assays showed that Chmp2a interacted with Skd1 in transfected HeLa cells, and the interaction did not require the N- or C-terminal coiled-coil domains of Chmp2a. Experiments using an ATPase-negative Skd1 mutant suggested that Chmp2a may play a role in associating Skd1 with the ESCRT-III complex. Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of human ESCRT-III components, including CHMP2A. CHMP2A interacted with VPS4A (609982) and LOC129531 (MITD1). Coimmunoprecipitation assays confirmed the interaction between CHMP2A and LOC129531, and the 2 proteins partially colocalized with M6PR (154540) on late endosomal membranes. The AAA ATPase Vps4 (see 609982) is central to endosomal traffic to lysosomes, retroviral budding, and cytokinesis, and dissociates ESCRT complexes from membranes. Obita et al. (2007) showed that, of the 6 ESCRT-III-related subunits in yeast, only Vps2 and Did2 bind the MIT (microtubule interacting and transport) domain of Vps4, and that the C-terminal 30 residues of the subunits are both necessary and sufficient for interaction. Lata et al. (2008) found that ESCRT-III proteins CHMP2A and CHMP3 (610052) could assemble in vitro into helical tubular structures that expose their membrane-interaction sites on the outside of the tubule, whereas the AAA-type adenosine triphosphatase VPS4 (609982) could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. CHMP2A and CHMP3 copolymerized in solution, and their membrane targeting was cooperatively enhanced on planar lipid bilayers. Lata et al. (2008) concluded that such helical CHMP structures could thus assemble within the neck of an inwardly budding vesicle, catalyzing late steps in budding under the control of VPS4. Olmos et al. (2015) demonstrated that the ESCRT-III machinery localizes to sites of annular fusion in the forming nuclear envelope in human cells, and is necessary for proper postmitotic nucleocytoplasmic compartmentalization. The ESCRT-III component CHMP2A is directed to the forming nuclear envelope through binding to CHMP4B (610897), and provides an activity essential for nuclear envelope reformation. Localization also requires the p97 complex (see 601023) member UFD1 ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610893 was added.