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    TSG101 tumor susceptibility 101 [ Homo sapiens (human) ]

    Gene ID: 7251, updated on 19-Sep-2024

    Summary

    Official Symbol
    TSG101provided by HGNC
    Official Full Name
    tumor susceptibility 101provided by HGNC
    Primary source
    HGNC:HGNC:15971
    See related
    Ensembl:ENSG00000074319 MIM:601387; AllianceGenome:HGNC:15971
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TSG10; VPS23
    Summary
    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]
    Expression
    Ubiquitous expression in testis (RPKM 34.7), adrenal (RPKM 31.6) and 25 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    See TSG101 in Genome Data Viewer
    Location:
    11p15.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (18480311..18526942, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (18578331..18624993, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (18501858..18548489, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene lactate dehydrogenase C Neighboring gene lactate dehydrogenase A like 6A Neighboring gene ReSE screen-validated silencer GRCh37_chr11:18507685-18507894 Neighboring gene tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4502 Neighboring gene UEV and lactate/malate dehyrogenase domains Neighboring gene ReSE screen-validated silencer GRCh37_chr11:18600575-18600756 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4504 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4505 Neighboring gene Sharpr-MPRA regulatory region 13786 Neighboring gene uncharacterized LOC112268073 Neighboring gene MTCH1 pseudogene 2

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 incorporates PDCD6IP (ALIX) and TSG101 into virions, which is sensitive to mutations in YP and PTAP domains respectively PubMed
    siRNA knockdown of TSG101 impairs terminal cleavage of p24/p2 to p24 and HIV release is impaired (from sequential transfection of siRNA followed by plasmid HIVdeltaEnv (pBH10)); HIV release is enhanced by TSG101 PubMed
    siRNA knockdown of TSG101 in U1/HIV-1 cells (chronically infected monocytoid cells harboring 2 integrated copies of HIV provirus per cell) decreases CA (p24) levels in supernatants but not intracellular CA (p24) levels PubMed
    Knockdown of tumor susceptibility gene 101 (TSG101) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef induces release of TSG101 (MAL-dependent exosome marker) from Jurkat T cells transfected with DNA constructs coding for Nef-GFP PubMed
    nef HIV-1 Nef is detected in detergent-insoluble AChE+/CD81 low/TSG101 low exosomes, but not in detergent-soluble AChE-/CD81 high/TSG101 high exosomes in Nef-transfected 293T cells PubMed
    nef HIV-1 Nef associates with TSG101 in extracellular vesicles isolated from HIV-1-infected patients PubMed
    Pr55(Gag) gag HIV-1 Gag incorporates PDCD6IP (ALIX) and TSG101 into virions PubMed
    gag Knockdown of TSG101 impairs terminal cleavage of p24/p2 to p24 PubMed
    gag Superresolution imaging of HIV-1 Gag and ESCRT proteins (TSG101, ALIX, CHMP4B, and CHMP4C) demonstrates in HeLa cells that Gag assemblages often has ESCRT proteins in their direct vicinity PubMed
    gag Three-dimensional superresolution microscopy and correlative electron microscopy demonstrate that the ESCRT proteins TSG101, CHMP2A, and CHMP4B co-cluster with membrane-localized HIV-1 Gag at assembly sites PubMed
    gag Tsg 101, VPS 28, and VPS 37B form the human endosomal sorting complex required for transport (ESCRT-I), which is required for HIV-1 Gag budding and virus infectivity PubMed
    gag Deletion of HIV-1 NC zinc-finger 2 motif in HIV-1 Gag impairs the recruitment of TSG101 at the plasma membrane and its incorporation into virions PubMed
    gag Released Gag VLPs contain TSG101 and CHMP4B, but reduced levels of CHMP2A relative to CHMP4B PubMed
    gag Fusion protein Dub-TSG101, the catalytic domain of the Herpes Simplex UL36 deubiquitinating enzyme (DUb) fused onto TSG101, inhibits HIV-1 release, which involes the interaction between HIV-1 Gag and TSG101 PubMed
    gag The interaction between HIV-1 Gag and TSG101 enhances tetherin recruitment in HeLa cells. Both TSG101 and ALIX binding sites within the p6 domain of Gag enhance tetherin recruitment to Gag assembly sites in T cells PubMed
    gag AIP1 binds to the LXXLF motif in HIV-1 p6 (amino acids 41-44) and also binds to TSG101 to act as a component of the viral budding machinery PubMed
    gag The direct binding of the UEV domain (amino acids 1-145) of TSG101 to the L domain (amino acids 7-10) of HIV-1 p6-Gag is essential for the p6 directed budding of HIV-1 virions from infected cells PubMed
    gag TSG101 binding to HIV-1 Gag correlates with redistribution of IP3R to the plasma membrane PubMed
    gag Tal, a Tsg101-associated ligase, binds and ubiquitylates Tsg101; Tal-mediated binding and ubiquitylation of Tsg101 cooperatively regulate release of HIV-1 Gag PubMed
    gag The p1 spacer peptide in HIV-1 Gag can confer a requirement for Tsg101 binding. Removal of NC-p1 region from authentic HIV-1 alleviates sensitivity to dominant-negative CHMP3 PubMed
    gag The PTAP sequence (179-182) in the GAT domain and the PSAP sequence (310-313) in the C-terminal region of Tom1L1 are required for its interaction with the UEV domain (1-145) of Tsg101 and competes with HIV-1 Gag PubMed
    gag Expression of HIV-1 Gag attenuates SDF-1-mediated downregulation of CXCR4. The effect of Gag is dependent on a TSG101 interacting motif within the C-terminal p6 region of Gag PubMed
    gag The Bro1 domain of Alix inhibits HIV budding by targeting both PTAP/TSG101 and LYPXnL/Alix pathways. The NC domain of Gag is the primary target for Bro1 inhibition by Gag-mediated recruitment of Bro1 to the plasma membrane PubMed
    gag A genetically selected cyclic peptide IYWNVSGW inhibits HIV budding by targeting the interaction between the p6 domain of Gag and TSG101. The inhibitory activity of the peptide is PT/SAP dependent PubMed
    gag The hydroxyl of the Thr or Ser residue in the P(S/T)AP motif of HIV-1 Gag forms hydrogen bonds with the main chain of Asn69. Mutation of the Asn to Pro abrogates PTAP motif binding to TSG101 and blocks budding of HIV-1 from cells PubMed
    gag The p6 domain of HIV-1 Gag mimics the Tsg101-recruiting activity of the human Hrs protein PubMed
    Vpr vpr HIV-1 Vpr competes with TSG101 to bind Gag PubMed
    vpr HIV-1 Vpr abrogates the effect of TSG101 overexpression to support virus like particle release PubMed
    Vpu vpu Physiological levels of Vpu requires the core ESCRT pathway (TSG1010 and UBAP1) and HGA (HRS) for Vpu-mediated BST-2 (tetherin) degradation but does not require these proteins for counteraction of BST2 (tetherin's) physical antiviral activity PubMed
    capsid gag siRNA knockdown of TSG101 in U1/HIV-1 cells (chronically infected monocytoid cells harboring 2 integrated copies of HIV provirus per cell) affects (decreases) CA (p24) levels in supernatants but not intracellular CA (p24) levels PubMed
    gag Knockdown of TSG101 impairs terminal cleavage of p24/p2 to p24 PubMed
    nucleocapsid gag Deletion of HIV-1 NC zinc-finger 2 motif in HIV-1 Gag impairs the recruitment of TSG101 at the plasma membrane (PM) and its incorporation into virions, suggesting NC-mediated recruitment of TSG101 to Gag assembly sites occur at the PM PubMed
    p2 gag A computational approach, based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions, predicts that HIV-1 gp41, IN, and the p2 region of Gag may all be able to interact with TSG101 PubMed
    gag Knockdown of TSG101 impairs terminal cleavage of p24/p2 to p24 PubMed
    p6 gag The direct binding of the UEV domain (amino acids 1-145) of TSG101 to the L domain (amino acids 7-10) of HIV-1 p6-Gag is essential for the p6 directed budding of HIV-1 virions from infected cells PubMed
    gag AIP1 binds to the LXXLF motif in HIV-1 p6 (amino acids 41-44) and also binds to TSG101 to act as a component of the viral budding machinery PubMed
    gag ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37), and a fourth subunit MVB12. Recombinant ESCRT-I complexes bind HIV-1 p6 PubMed
    gag Employing N-alkylglycine ('peptoid') residues to the p6-derived 9-mer sequence 'PEPTAPPEE' improves peptide binding affinity to the ubiquitin E2 variant domain of TSG101 PubMed
    gag NEDD4L-mediated stimulation of virus budding is dependent upon the ubiquitin ligase activity of NEDD4L and requires only the minimal HIV-1 Gag assembly regions and TSG101 PubMed
    gag Expression of HIV-1 Gag attenuates SDF-1-mediated downregulation of CXCR4. This effect of Gag is dependent on a TSG101 interacting motif within the C-terminal p6 region of Gag PubMed
    gag A genetically selected cyclic peptide IYWNVSGW inhibits HIV budding by targeting the interaction between the p6 domain of Gag and TSG101. The inhibitory activity of the peptide is PT/SAP dependent PubMed
    gag The hydroxyl of the Thr or Ser residue in the P(S/T)AP motif of HIV-1 p6 forms hydrogen bonds with the main chain of Asn69. Mutation of the Asn to Pro abrogates PTAP motif binding to TSG101 and blocks budding of HIV-1 from cells PubMed
    gag The p6 domain of HIV-1 Gag mimics the Tsg101-recruiting activity of the human Hrs protein PubMed
    gag A short helix (helix-1; amino acid residues 14-18) in HIV-1 p6 enhances the binding of the p6 PTAP motif (residues 7-10) to TSG101 PubMed
    reverse transcriptase gag-pol HIV-1 late RT activity is specifically increased by siRNA-mediated knockdown of TSG101 expression, showing that TSG101 inhibits HIV-1 from reverse transcribing its genome into DNA prior to virus release PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables calcium-dependent protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein-containing complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transcription corepressor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ubiquitin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables virion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in autophagosome maturation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endosome to lysosome transport IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in exosomal secretion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in extracellular transport IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in keratinocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in macroautophagy TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in membrane fission NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in multivesicular body assembly NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in multivesicular body assembly TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of epidermal growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of epidermal growth factor-activated receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of exosomal secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of ubiquitin-dependent endocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of viral budding via host ESCRT complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein modification process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of MAP kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of cell growth IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of extracellular exosome assembly IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IC
    Inferred by Curator
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in viral budding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in viral budding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in viral budding via host ESCRT complex TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in viral release from host cell IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of ESCRT I complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of ESCRT I complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of ESCRT I complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of ESCRT I complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of ESCRT I complex TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in Flemming body IEA
    Inferred from Electronic Annotation
    more info
     
    located_in centrosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in early endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in early endosome membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endosome membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in late endosome IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    located_in late endosome membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in multivesicular body TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    tumor susceptibility gene 101 protein
    Names
    ESCRT-I complex subunit TSG101
    tumor susceptibility gene 10
    tumor susceptibility gene 101
    tumor susceptibility protein

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012138.2 RefSeqGene

      Range
      5001..51632
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006292.4NP_006283.1  tumor susceptibility gene 101 protein

      See identical proteins and their annotated locations for NP_006283.1

      Status: REVIEWED

      Source sequence(s)
      BP347883, CB528488, U82130
      Consensus CDS
      CCDS7842.1
      UniProtKB/Swiss-Prot
      Q99816, Q9BUM5
      UniProtKB/TrEMBL
      F5H442
      Related
      ENSP00000251968.3, ENST00000251968.4
      Conserved Domains (3) summary
      pfam05743
      Location:21139
      UEV; UEV domain
      pfam07798
      Location:236292
      DUF1640; Protein of unknown function (DUF1640)
      pfam09454
      Location:316375
      Vps23_core; Vps23 core domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      18480311..18526942 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005253108.5XP_005253165.1  tumor susceptibility gene 101 protein isoform X1

      See identical proteins and their annotated locations for XP_005253165.1

      UniProtKB/TrEMBL
      F5H442
      Conserved Domains (3) summary
      pfam05743
      Location:187
      UEV; UEV domain
      pfam07798
      Location:184240
      DUF1640; Protein of unknown function (DUF1640)
      pfam09454
      Location:264323
      Vps23_core; Vps23 core domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      18578331..18624993 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369804.1XP_054225779.1  tumor susceptibility gene 101 protein isoform X1

      UniProtKB/TrEMBL
      F5H442