Charged multivesicular body protein 1b (CHMP1B)

The protein contains 199 amino acids for an estimated molecular weight of 22109 Da.

 

Probable peripherally associated 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. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B and SPAST to the midbody of dividing cells. Involved in HIV-1 p6- and p9-dependent virus release. (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.

Interpro domains
Total structural coverage: 26%
Model score: 0

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The reference OMIM entry for this protein is 606486

Chmp family, member 1b; chmp1b
Chromatin-modifying protein 1b
Charged multivesicular body protein 1b
Chromosome 18 open reading frame 2; c18orf2

DESCRIPTION

CHMP1B 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 in silico gene trapping, Vuoristo et al. (2001) identified a novel gene, designated C18ORF2, embedded in exon 5 of the GNAL gene (139312) on chromosome 18p11. The C18ORF2 gene encodes a deduced 199-amino acid protein with a predicted molecular mass of 22.1 kD. The protein is highly conserved across several species and shares 55% sequence identity with the PRSM1 gene (CHMP1A). RT-PCR analysis detected moderate expression of C18ORF2 in all tissues tested.

GENE FUNCTION

Scott et al. (2005) found that the C-terminal half of the endosomal sorting complex protein CHMP1B bound the microtubule-interacting and transport (MIT) domain of VPS4A (609982). Using a yeast 2-hybrid approach, Reid et al. (2005) identified CHMP1B as a binding partner of spastin (SPAST; 604277), mutations in which are the most common cause of hereditary spastic paraplegia, which results in degeneration of long axons. CHMP1B and spastin proteins showed clear cytoplasmic colocalization in transfected cells; CHMP1B and spastin proteins interacted specifically in vitro and in vivo in complementation assays, and spastin coimmunoprecipitated with CHMP1B. The interaction was mediated by a region of spastin lying between residues 80 and 196 and containing an MIT domain. Expression of epitope-tagged CHMP1B in mammalian cells prevented the development of the abnormal microtubule phenotype associated with expression of ATPase-defective spastin. The authors suggested a role for spastin in intracellular membrane traffic events, and proposed that defects in intracellular membrane traffic may be a significant cause of motor neuron pathology. Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of human ESCRT-III components, including CHMP1B. The novel CHMP1B-binding partners included SSRP1 (604328), which may be involved in chromatin remodeling, TRAF4AF1, which may be involved in signal transduction, and AMSH (606247). Coimmunoprecipitation assays confirmed the interaction between CHMP1B and AMSH, and the 2 proteins partially colocalized with M6PR (154540) on late endosomal membranes. Using yeast 2-hybrid screens, followed by coimmunoprecipitation and protein-binding assays, Bajorek et al. (2009) found that human IST1 (616434) interacted with several ESCRT proteins, including CHMP1A and CHMP1B, as well as with VPS4A and VPS4B (609983). IST1 bound CHMP1 directly, and like IST1, CHMP1 has a C-terminal MIM element that bound VPS4 MIT domains. Depletion of either IST1 or CHMP1 in HeLa cells blocked VPS4 recruitment to the midbody during cytokinesis and blocked cell division. Time-lapse imaging revealed that IST1 depletion caused dividing cells to arrest during the abscission stage. Cells remained tethered together through their midbodies before eventually recoalescing into a single cell with multiple nuclei. Bajorek et al. (2009) concluded that IST1 is specifically required for the cytokinesis function of ESC ... 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 606486 was added.

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