Charged multivesicular body protein 4b (CHMP4B)

The protein contains 224 amino acids for an estimated molecular weight of 24950 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 (PubMed:12860994, PubMed:18209100). 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). Plays a role in the endosomal sorting pathway. 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 CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).', '(Microbial infection) The ESC (updated: Nov. 22, 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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 46%
Model score: 37
MODL_I-TASSER-3.0

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VariantDescription
CTRCT31
CTRCT31

The reference OMIM entry for this protein is 605387

Cataract 31, multiple types; ctrct31
Cataract, posterior polar, 3; ctpp3; cpp3

A number sign (#) is used with this entry because of evidence that multiple types of cataract are caused by heterozygous mutation in the CHMP4B gene (610897) on chromosome 20q11.

DESCRIPTION

Mutations in the CHMP4B gene have been found to cause multiple types of cataract, which have been described as posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular. The preferred title/symbol of this entry was formerly 'Cataract, Posterior Polar, 3; CTPP3.'

CLINICAL FEATURES

Yamada et al. (2000) described a Japanese family in which 10 members in 4 generations were affected with autosomal dominant posterior polar cataract. The cataract was characterized by progressive, disc-shaped, posterior subcapsular opacity. Shiels et al. (2007) reported 15 affected individuals in a large 6-generation Caucasian family with progressive childhood posterior subcapsular cataracts. Cataracts progressed with age to affect the nucleus and anterior subcapsular regions of the lens. Age at diagnosis varied from 4 to 20 years.

MAPPING

By linkage analysis of the Japanese family with cataract described by Yamada et al. (2000), Yamada et al. (2000) assigned the locus, which they designated CPP3, to chromosome 20p12-q12. Shiels et al. (2007) performed linkage analysis in a large 6-generation Caucasian family with autosomal dominant progressive childhood posterior subcapsular cataract and, after excluding known autosomal dominant cataract loci, found significant linkage on chromosome 20q with a maximum 2-point lod score of 5.50 at D20S847. Analysis of recombinant events in affected individuals followed by genotyping with biallelic SNP markers narrowed the region of interest to a 0.9-Mb interval containing approximately 80 genes, none of which were obvious functional candidates for cataracts.

MOLECULAR GENETICS

In a large 6-generation Caucasian family with autosomal dominant progressive childhood posterior subcapsular cataract mapping to chromosome 20q, Shiels et al. (2007) sequenced positional candidate genes and identified a heterozygous mutation in the CHMP4B gene (D129V; 610897.0001) that cosegregated with disease and was not found in 384 control chromosomes. The mutation was not found in unaffected family members except for a 17-year-old male who was believed to be either nonpenetrant or presymptomatic. Shiels et al. (2007) also identified a heterozygous mutation (E161K; 610897.0002) in the CHMP4B gene in affected individuals of the Japanese family previously reported by Yamada et al. (2000) and Yamada et al. (2000). - Exclusion Studies In a Japanese family with cataract mapping to chromosome 20p12-q12, Yamada et al. (2000) performed sequence analysis on the entire coding region of the BFSP1 gene (603307), but found no base substitutions or deletions. ... 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 605387 was added.

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