TSG101

TSG101
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KPP, 1KPQ, 1M4P, 1M4Q, 1S1Q, 2F0R, 3IV1, 3OBQ, 3OBS, 3OBU, 3OBX, 3P9G, 3P9H, 4EJE, 4YC1, 4ZNY
Identifiers
Aliases	TSG101, TSG10, VPS23, tumor susceptibility 101
External IDs	OMIM: 601387; MGI: 106581; HomoloGene: 4584; GeneCards: TSG101; OMA:TSG101 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.1 Start 18,468,336 bp[1] End 18,526,951 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B3 Start 46,538,697 bp[2] End 46,569,717 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte ganglionic eminence islet of Langerhans amniotic fluid gastrocnemius muscle rectum parotid gland right uterine tube left adrenal gland Top expressed in ganglionic eminence maxillary prominence neural tube medial ganglionic eminence lip abdominal wall esophagus primitive streak superior cervical ganglion atrium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein homodimerization activity transcription corepressor activity calcium-dependent protein binding ubiquitin binding protein binding nuclear receptor coactivator activity virion binding ubiquitin protein ligase binding protein-containing complex binding Cellular component cytoplasm multivesicular body endosome late endosome membrane late endosome membrane plasma membrane early endosome nucleolus endosome membrane extracellular exosome ESCRT I complex nucleus cytosol host cell microtubule organizing center cytoskeleton early endosome membrane Flemming body Biological process intracellular transport of virus cell differentiation positive regulation of ubiquitin-dependent endocytosis regulation of extracellular exosome assembly viral budding via host ESCRT complex viral life cycle endosome to lysosome transport multivesicular body assembly protein monoubiquitination viral budding keratinocyte differentiation cell division endosomal transport autophagosome maturation regulation of cell growth protein transport ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway regulation of MAP kinase activity positive regulation of exosomal secretion cell cycle regulation of growth negative regulation of transcription, DNA-templated negative regulation of cell population proliferation viral process exosomal secretion macroautophagy negative regulation of epidermal growth factor receptor signaling pathway negative regulation of epidermal growth factor-activated receptor activity transport extracellular transport positive regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7251 22088 Ensembl ENSG00000074319 ENSMUSG00000014402 UniProt Q99816 Q61187 RefSeq (mRNA) NM_006292 NM_021884 NM_001348088 NM_001348089 RefSeq (protein) NP_006283 NP_068684 NP_001335017 NP_001335018 Location (UCSC) Chr 11: 18.47 – 18.53 Mb Chr 7: 46.54 – 46.57 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.

Function

The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.^[5]

The main role of TSG101 is to participate in ESCRT pathway. This pathway facilitates reverse topology budding and formation of multivesicular bodies (MVB) which delivers cargo destined for degradation to the lysosomes.^[6] TSG101 recognises short linear motif : P(T/S)AP via the UEV protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions.^[7][8]

Viral Hijacking

TSG101 plays an important role in the pathogenesis of HIV and other viruses. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB),^[9] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.^[10]

Interactions

TSG101 has been shown to interact with:

• EP300,^[11]
• HGS,^[12][13]
• LRSAM1,^[12][14]
• P21,^[15]
• P53,^[16] and
• VPS28.^[12][17][18]

Orthologue, Vps23

Vps23_core
escrt-i core
Identifiers
Symbol	Vps23_core
Pfam	PF09454
InterPro	IPR017916
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

In humans, the orthologue of vps23 which has a component of ESCRT-1 is called Tsg101. Mutations in Tsg-101 have been linked to cervical, breast, prostate and gastrointestinal cancers. In molecular biology, vps23 (vacuolar protein sorting) is a protein domain. Vps proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. More specifically, vps23 is a component of ESCRT-I. The ESCRT complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis and budding of HIV.

Structure

Yeast ESCRT-I consists of three protein subunits, VPS23, VPS28, and VPS37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues.

See also

• FGI-104 - an ESCRT inhibitor being researched as a broad spectrum antiviral

References

Further reading