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Tumor susceptibility 101
Protein TSG101 PDB 1kpp.png
PDB rendering based on 1kpp.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TSG101 ; TSG10; VPS23
External IDs OMIM601387 MGI106581 HomoloGene4584 ChEMBL: 6157 GeneCards: TSG101 Gene
RNA expression pattern
PBB GE TSG101 201758 at tn.png
More reference expression data
Species Human Mouse
Entrez 7251 22088
Ensembl ENSG00000074319 ENSMUSG00000014402
UniProt Q99816 Q61187
RefSeq (mRNA) NM_006292 NM_021884
RefSeq (protein) NP_006283 NP_068684
Location (UCSC) Chr 11:
18.49 – 18.55 Mb
Chr 7:
46.89 – 46.92 Mb
PubMed search [1] [2]

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


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.[1]

The main role of ESCRT-I is to recognise ubiquitinated cargo 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.[2][3]


TSG101 seems to play an important role in the pathogenesis of HIV. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB),[4] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.[5]


TSG101 has been shown to interact with:

Orthologue, Vps23[edit]

PDB 2caz EBI.jpg
escrt-i core
Symbol Vps23_core
Pfam PF09454
InterPro IPR017916

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.


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[edit]


  1. ^ "Entrez Gene: TSG101 tumor susceptibility gene 101". 
  2. ^ Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB, Vallis Y et al. (April 2006). "ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes". Cell 125 (1): 99–111. doi:10.1016/j.cell.2006.01.047. PMID 16615893. 
  3. ^ Kostelansky MS, Sun J, Lee S, Kim J, Ghirlando R, Hierro A et al. (April 2006). "Structural and functional organization of the ESCRT-I trafficking complex". Cell 125 (1): 113–26. doi:10.1016/j.cell.2006.01.049. PMC 1576341. PMID 16615894. 
  4. ^ Katzmann DJ, Odorizzi G, Emr SD (2002). "Receptor downregulation and multivesicular-body sorting". Nat. Rev. Mol. Cell Biol. 3 (12): 893–905. doi:10.1038/nrm973. PMID 12461556. 
  5. ^ von Schwedler UK, Stuchell M, Müller B, Ward DM, Chung HY, Morita E et al. (2003). "The protein network of HIV budding". Cell 114 (6): 701–13. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570. 
  6. ^ Sun Z, Pan J, Hope WX, Cohen SN, Balk SP (August 1999). "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer 86 (4): 689–96. doi:10.1002/(sici)1097-0142(19990815)86:4<689::aid-cncr19>3.0.co;2-p. PMID 10440698. 
  7. ^ a b c Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  8. ^ Lu Q, Hope LW, Brasch M, Reinhard C, Cohen SN (June 2003). "TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation". Proc. Natl. Acad. Sci. U.S.A. 100 (13): 7626–31. doi:10.1073/pnas.0932599100. PMC 164637. PMID 12802020. 
  9. ^ Amit I, Yakir L, Katz M, Zwang Y, Marmor MD, Citri A et al. (July 2004). "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding". Genes Dev. 18 (14): 1737–52. doi:10.1101/gad.294904. PMC 478194. PMID 15256501. 
  10. ^ Oh H, Mammucari C, Nenci A, Cabodi S, Cohen SN, Dotto GP (April 2002). "Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1)". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5430–5. doi:10.1073/pnas.082123999. PMC 122786. PMID 11943869. 
  11. ^ Li L, Liao J, Ruland J, Mak TW, Cohen SN (February 2001). "A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1619–24. doi:10.1073/pnas.98.4.1619. PMC 29306. PMID 11172000. 
  12. ^ Stuchell MD, Garrus JE, Müller B, Stray KM, Ghaffarian S, McKinnon R et al. (August 2004). "The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding". J. Biol. Chem. 279 (34): 36059–71. doi:10.1074/jbc.M405226200. PMID 15218037. 
  13. ^ Bishop N, Woodman P (April 2001). "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. 276 (15): 11735–42. doi:10.1074/jbc.M009863200. PMID 11134028. 

Further reading[edit]