Description: Homo sapiens tumor susceptibility gene 101 (TSG101), mRNA. RefSeq Summary (NM_006292): 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. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr11:18,501,858-18,548,503 Size: 46,646 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr11:18,502,093-18,548,363 Size: 46,271 Coding Exon Count: 10
ID:TS101_HUMAN DESCRIPTION: RecName: Full=Tumor susceptibility gene 101 protein; AltName: Full=ESCRT-I complex subunit TSG101; FUNCTION: 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. SUBUNIT: Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and a FAM125/MVB12 protein (FAM125A or -B) in a 1:1:1:1 stoechiometry. Interacts with VPS37A, VPS37B and VPS37C. Interacts with ubiquitin, stathmin, GMCL, DMAP1 and AATF (By similarity). Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex. Interacts with GGA1 and GGA3. Interacts (via UEV domain) with PDCD6IP/AIP1. Interacts with VPS28, SNF8 and VPS36. Self-associates. Interacts with FAM125A/MVB12A; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts with CEP55; the interaction is required for cytokinesis but not for viral budding. Interacts with PDCD6. Interacts with HIV-1 p6. Interacts with human spumavirus Gag. Interacts with HTLV-1 Gag. Interacts with Ebola virus VP40. Interacts with EIAV p9; the interaction has been shown in vitro. Interacts with MGRN1. INTERACTION: Q9UER7:DAXX; NbExp=4; IntAct=EBI-346882, EBI-77321; Q99732:LITAF; NbExp=3; IntAct=EBI-346882, EBI-725647; Q9UK41:VPS28; NbExp=3; IntAct=EBI-346882, EBI-727424; SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Late endosome membrane; Peripheral membrane protein. Note=Mainly cytoplasmic. Membrane-associated when active and soluble when inactive. Depending on the stage of the cell cycle, detected in the nucleus. Colocalized with CEP55 in the midbody during cytokinesis. TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas. DOMAIN: The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein. DOMAIN: The coiled coil domain may interact with stathmin. DOMAIN: The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently. PTM: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1. SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily. SIMILARITY: Contains 1 SB (steadiness box) domain. SIMILARITY: Contains 1 UEV (ubiquitin E2 variant) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99816
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003677 DNA binding GO:0003714 transcription corepressor activity GO:0005515 protein binding GO:0030374 ligand-dependent nuclear receptor transcription coactivator activity GO:0031625 ubiquitin protein ligase binding GO:0042803 protein homodimerization activity GO:0043130 ubiquitin binding GO:0044877 macromolecular complex binding GO:0046790 virion binding GO:0048306 calcium-dependent protein binding
Biological Process: GO:0001558 regulation of cell growth GO:0006464 cellular protein modification process GO:0006513 protein monoubiquitination GO:0006858 extracellular transport GO:0007049 cell cycle GO:0007050 cell cycle arrest GO:0007175 negative regulation of epidermal growth factor-activated receptor activity GO:0008285 negative regulation of cell proliferation GO:0008333 endosome to lysosome transport GO:0015031 protein transport GO:0016032 viral process GO:0016197 endosomal transport GO:0016236 macroautophagy GO:0019058 viral life cycle GO:0030154 cell differentiation GO:0030216 keratinocyte differentiation GO:0036258 multivesicular body assembly GO:0039702 viral budding via host ESCRT complex GO:0040008 regulation of growth GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway GO:0043405 regulation of MAP kinase activity GO:0045892 negative regulation of transcription, DNA-templated GO:0046755 viral budding GO:0048524 positive regulation of viral process GO:0051301 cell division GO:0097352 autophagosome maturation GO:1902188 positive regulation of viral release from host cell GO:1903543 positive regulation of exosomal secretion GO:1903551 regulation of extracellular exosome assembly GO:1903772 regulation of viral budding via host ESCRT complex GO:1903774 positive regulation of viral budding via host ESCRT complex GO:1990182 exosomal secretion GO:2000397 positive regulation of ubiquitin-dependent endocytosis GO:1902186 regulation of viral release from host cell
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
