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FLASH GENE
Symbol TSG101 contributors: mct/npt - updated : 23-09-2015
HGNC name tumor susceptibility gene 101
HGNC id 15971
Location 11p15.1      Physical location : 18.501.859 - 18.548.489
Synonym name
  • vesicular protein sorting 23
  • endometrial, hormone refractory prostate cancer
  • tumor susceptibility gene 10
  • ESCRT-I complex subunit TSG101
    • Synonym symbol(s) CC2, D11S2247E, VPS23, TSG10
    DNA
    TYPE functioning gene
    STRUCTURE 46.63 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D11S921 - TSG101 - D11S899 - D11S1308 - D11S1359 - cen
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1550 43.8 390 - 2009 19520058
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
     parathyroid   highly
    Reproductivefemale systemovary  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • proline-rich domain
  • DNA binding motifs
  • a coiled-coil domain
  • Pro-rich regions that are bound by PDCD6 Ca2+-dependently (Okumura 2009)
  • putative dominant negative ubiquitin regulator with alternatively spliced isoforms (an isoform of 17kDa TSG101B without the C terminal leucine zipper, detected in Burkitt lymphoma)
  • C-terminal lysines are targets for polyubiquitination, but they are not required for any additional function necessary for ESCRT activity (McDonald 2008), and C-terminal steadiness box (SB) involved in the repression of CDKN1A promoter activity
    • HOMOLOGY
    interspecies homolog to murine tumor susceptibility gene 101 (Tsg101)
    Homologene
    FAMILY
  • ubiquitin-conjugating enzyme family
  • UEV subfamily
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • involved in cell cycle regulation
  • transcriptional suppressor for ESRR and other nuclear hormone receptors
  • playing a crucial role for cell proliferation and cell survival
  • activating androgen receptor-induced transcription by transient stabilization of the monoubiquitinated state (novel regulatory mechanism for nuclear receptors)
  • function at the endosome to help sort membrane proteins into vesicles that bud into the lumen to create multivesicular bodies
  • regulates vesicular trafficking processes (Amit 2004)
  • essential for endosomal sorting, membrane receptor degradation and the final stages of cytokinesis (McDonald 2008)
  • is one of the cellular proteins involved in the budding process of HIV-1, and plays an important role in the cellular vacuolar protein sorting (Vps) pathway
  • essential ESCRT component, that is central to endosomal sorting
  • is recruited by a late domain of the nucleocapsid protein to support budding of Marburg virus-like particles
  • may play a biological role through modulation of the MAPK/ERK signaling pathway in breast cancer
  • is involved in numerous cellular processes, including apoptotic resistance
  • RAB7A and TSG101 are required for the constitutive recycling of unliganded EGFRs via distinct mechanisms
  • multi-domain protein known to act in the cell nucleus, cytoplasm, and periplasmic membrane
  • its functions additionally are recruited for viral and microvesicle budding and for intracellular survival of invading bacteria
    • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with DAXX through its coiled-coil domain and co-localized in the nucleus
  • functions as a subunit of the heterotetrameric ESCRT-I complex (Endosomal Sorting Complex Required for Transport-I), together with two other MVB (multivesicular body) pathway proteins: VPS28, VPS37B
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DAXX
  • interacting with AATF (functioning as cooperative coactivators in androgen receptor-mediated transcription)
  • with three proteins involved in cytokinesis, CD2AP, ROCK1, and IQGAP
  • interacting with PDCD6IP (Ca2+-loaded PDCD6 bridges PDCD6IP and TSG101 as an adaptor protein) (Okumura 2009)
  • is a novel RAB11FIP4-binding protein, which we find can also bind RAB11FIP3
  • specific interaction of TSG101 with a tetrapeptide PSAP motif of ARRDC1, which is localized to the plasma membrane through its arrestin domain
  • UBAP1, a subunit of human ESCRT-I, coassembles in a stable 1:1:1:1 complex with TSG101, VPS28, and VPS37A
  • LITAF interacted and colocalized with endosomal sorting complex required for transport (ESCRT) components STAM1, HGS, and TSG101 on early endosomes and functioned with the ESCRT machinery in the control of endosome-to-lysosome trafficking
  • interacts with and down-regulates the promoter of CDKN1A tumor suppressor gene
  • genetic interaction of BBS1 and BBS4 with the endosomal sorting complexes required for transport (ESCRT) gene TSG101 and accumulation of receptor in late endosomes, reduced endosomal recycling and reduced receptor degradation in lysosomes
  • BLOC1S1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking
  • LRSAM1 is a regulator of TSG101 expression
    • cell & other
    REGULATION
    Other regulated by LRSAM1 (polyubiquitinates lysine residues in the C-terminus of uncomplexed TSG101, resulting in proteasomal degradation) (McDonald 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    mutated in primary breast carcinoma
    tumoral     --over  
    overexpressed in papillary thyroid carcinomas
    tumoral somatic mutation      
    in small cell lung carcinoma and in cervical, endometrial, hormone refractory prostate cancers
    tumoral     --over  
    in colorectal carcinoma (Ma 2008)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • positive expression of PEG10 or TSG101 is a predictor of poor prognosis in gallbladder adenocarcinoma
    • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    is a potentially new attractive target for therapeutic intervention in AIDS
    ANIMAL & CELL MODELS