Tumor susceptibility gene 101 protein (TSG101)
The protein contains 390 amino acids for an estimated molecular weight of 43944 Da.
Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs34385327 |
Biological Process
Autophagosome maturation
Cell cycle arrest
Cell division
Cellular protein modification process
Endosomal transport
Endosome to lysosome transport
Exosomal secretion
Extracellular transport
Intracellular transport of virus
Keratinocyte differentiation
Macroautophagy
Membrane organization
Multivesicular body assembly
Negative regulation of cell population proliferation
Negative regulation of epidermal growth factor receptor signaling pathway
Negative regulation of epidermal growth factor-activated receptor activity
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription, DNA-templated
Positive regulation of exosomal secretion
Positive regulation of ubiquitin-dependent endocytosis
Positive regulation of viral budding via host ESCRT complex
Positive regulation of viral process
Positive regulation of viral release from host cell
Protein monoubiquitination
Protein transport
Regulation of cell growth
Regulation of extracellular exosome assembly
Regulation of MAP kinase activity
Regulation of viral budding via host ESCRT complex
Ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Viral budding
Viral budding via host ESCRT complex
Viral life cycle
Viral process
Viral protein processing
Virion assembly
The reference OMIM entry for this protein is 601387
Tumor susceptibility gene 101; tsg101
Vacuolar protein sorting 23, yeast, homolog of; vps23
CLONING
Using a strategy that enabled the isolation of previously unknown genes encoding selectable recessive phenotypes, Li and Cohen (1996) identified in the mouse a gene whose homozygous functional disruption by insertional mutagenesis and antisense RNA synthesis produced cell transformation. In their strategy, expression of a selectable marker in mouse 3T3 cells was dependent upon insertion of a gene search vector downstream of the promoter of randomly targeted chromosomal genes. Transactivation of a promoter on the noncoding strand of the search vector resulted in expression of antisense RNA that was complementary to the coding strand of the targeted allele, resulting in functional inactivation of the other allele. They subsequently selected for clonal colonies that gained the ability to grow in 0.5% agar and formed metastatic tumors in nude mice. Li and Cohen (1996) isolated such a clonal colony and designated the inactivated gene Tsg101. Removal of the transactivator required for antisense RNA expression restored normal growth, presumably because of subsequent loss of expression of the antisense transcripts complementary to Tsg101. The protein encoded by the Tsg101 cDNA contains a coiled-coil domain that interacts with stathmin (151442), a cytosolic phosphoprotein implicated in tumorigenesis. Li and Cohen (1996) observed that overexpression of Tsg101 antisense transcripts in NIH 3T3 cells resulted in cell transformation and increased stathmin-specific mRNA. Li et al. (1997) determined that the human TSG101 gene encodes a 381-amino acid polypeptide of 42.8 kD which is 94% identical to the mouse protein. By database searching and comparison of the TSG101 proteins of yeast and other organisms, Koonin and Abagyan (1997) concluded that TSG101 may belong to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. Wagner et al. (2003) stated that many of the TSG101 transcripts associated with human malignancies are actually alternatively spliced forms generated by exon skipping.GENE FUNCTION
Like other enveloped viruses, human immunodeficiency virus (HIV)-1 uses cellular machinery to bud from infected cells. Garrus et al. (2001) showed that TSG101, which functions in vacuolar protein sorting (VPS), is required for HIV-1 budding. The ubiquitin enzyme-2 variant (UEV) domain of TSG101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein of HIV-1 and also to ubiquitin. Depletion of cellular TSG101 by small interfering RNA arrested HIV-1 budding at a late stage, and budding was rescued by reintroduction of TSG101. Dominant-negative mutant VPS4 proteins that inhibit vacuolar protein sorting also arrested HIV-1 and MLV (murine leukemia virus) budding. These observations suggested that retroviruses bud by appropriating cellular machinery normally used in the VPS pathway to form multivesicular bodies. Amit et al. (2004) showed that LRSAM1 (610933) binds the TSG101 SB (steadiness box) and UEV regions. LRSAM1 ubiquitylates TSG101 both in HEK293T cells and in vitro, and multiple monomeric ubiquitylation of TSG101 results in inactivation of TSG101 sorting function. Studies of receptor endocytosis and virus budding suggested that LRSAM1 enables recycling of TSG101-containing sorting complexes and cargo reloading. In Drosophila cells, Moberg et al. (2005) showed that Tsg101 mutations activated Notch (see NOTCH1; 190198) signaling and caused overproduction of a secret ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601387 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed