Charged multivesicular body protein 4a (CHMP4A)

The protein contains 222 amino acids for an estimated molecular weight of 25098 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. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). (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. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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: 46%
Model score: 48
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs2295322

The reference OMIM entry for this protein is 610051

Chmp family, member 4a; chmp4a
Chromatin-modifying protein 4a
Charged multivesicular body protein 4a
Chmp4
Snf7, yeast, homolog of, 1
Snf7-1
Hspc134

DESCRIPTION

CHMP4A 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 the N-terminal region of ALIX (PDCD6IP; 608074) as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, Katoh et al. (2003) cloned CHMP4A. The deduced 223-amino acid protein has 3 coiled-coil regions, a basic N-terminal half, and an acidic C-terminal half. By Northern blot analysis, Katoh et al. (2004) detected a 1-kb CHMP4A transcript in all tissues examined, with highest expression in heart and moderate expression in skeletal muscle, kidney, and liver. By PCR of a human melanoma cDNA library, Lin et al. (2005) cloned CHMP4A, which they designated SNF7-1. They identified 2 PxxP motifs near the C terminus of CHMP4A. Northern blot analysis detected CHMP4A expression in all tissues examined, with highest levels in kidney, liver, skeletal muscle, and heart.

GENE FUNCTION

By yeast 2-hybrid analysis, Katoh et al. (2003) found that CHMP4A interacted with ALIX. Lin et al. (2005) found that overexpressed SNF7-1 associated with COS-7 cell membranes and perturbed normal multivesicular body biogenesis. The N-terminal half of SNF7-1 localized to membranes and formed detergent-resistant polymers, whereas the C-terminal half associated with the ESCRT-III component SKD1 (VPS4B; 609983). Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of human ESCRT-III components, including CHMP4A. CHMP4A interacted with the ESCRT-III protein VPS4A (609982) and with the signal transduction molecule CC2D1A (610055). In S. cerevisiae, ESCRT-III consists of Vps20 (610901), Snf7, Vps24 (610052), and Vps2 (610893), which assemble in that order and require the ATPase Vps4 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

By genomic sequence analysis, Katoh et al. (2003) mapped the CHMP4A gene to chromosome 14q11.2. ... 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 610051 was added.

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