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TSG101 tumor susceptibility 101 [ Homo sapiens (human) ]

Gene ID: 7251, updated on 8-Jul-2018
Official Symbol
TSG101provided by HGNC
Official Full Name
tumor susceptibility 101provided by HGNC
Primary source
HGNC:HGNC:15971
See related
Ensembl:ENSG00000074319 MIM:601387; Vega:OTTHUMG00000167725
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
See TSG101 in Genome Data Viewer
Location:
11p15.1
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (18480311..18526956, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (18501858..18548503, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene lactate dehydrogenase C Neighboring gene lactate dehydrogenase A like 6A Neighboring gene tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta pseudogene 2 Neighboring gene UEV and lactate/malate dehyrogenase domains Neighboring gene uncharacterized LOC112268073 Neighboring gene mitochondrial carrier 1 pseudogene

  • Project title: 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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

  • Assembly Of The HIV Virion, organism-specific biosystem (from REACTOME)
    Assembly Of The HIV Virion, organism-specific biosystemVirion assembly packages all the components required for infectivity. These steps include two copies of the positive sense genomic viral RNA, cellular tRNALys, the viral envelope (Env) protein, the G...
  • Budding and maturation of HIV virion, organism-specific biosystem (from REACTOME)
    Budding and maturation of HIV virion, organism-specific biosystemWith the virus components precariously assembled on the inner leaflet of the plasma membrane, the host cell machinery is required for viral budding. The virus takes advantage of the host ESCRT pathwa...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • ESCRT-I complex, organism-specific biosystem (from KEGG)
    ESCRT-I complex, organism-specific biosystemStructural complex; Genetic information processing; Protein processing
  • ESCRT-I complex, conserved biosystem (from KEGG)
    ESCRT-I complex, conserved biosystemStructural complex; Genetic information processing; Protein processing
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystem (from REACTOME)
    Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystemMany plasma membrane proteins are in a constant flux throughout the internal trafficking pathways of the cell. Some receptors are continuously internalized into recycling endosomes and returned to th...
  • Glucocorticoid receptor regulatory network, organism-specific biosystem (from Pathway Interaction Database)
    Glucocorticoid receptor regulatory network, organism-specific biosystem
    Glucocorticoid receptor regulatory network
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • HIV Life Cycle, organism-specific biosystem (from REACTOME)
    HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Internalization of ErbB1, organism-specific biosystem (from Pathway Interaction Database)
    Internalization of ErbB1, organism-specific biosystem
    Internalization of ErbB1
  • Late Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
    Late Phase of HIV Life Cycle, organism-specific biosystemThe late phase of the HIV-1 life cycle includes the regulated expression of the HIV gene products and the assembly of viral particles. The assembly of viral particles will be covered in a later relea...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Membrane binding and targetting of GAG proteins, organism-specific biosystem (from REACTOME)
    Membrane binding and targetting of GAG proteins, organism-specific biosystemOne of the mysteries of Gag protein involvement in HIV virion assembly is how the proteins are targeted to the proper membrane for budding. Infectious retroviruses do not bud from all of the availabl...
  • Synthesis And Processing Of GAG, GAGPOL Polyproteins, organism-specific biosystem (from REACTOME)
    Synthesis And Processing Of GAG, GAGPOL Polyproteins, organism-specific biosystemEvidence suggests that the RNA molecules used for the synthesis of Gag and Gag-Pro-Pol are not the same molecules that are packaged into virions. Gag proteins do not appear to aggregate around and ca...
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding TAS
Traceable Author Statement
more info
PubMed 
calcium-dependent protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
nuclear receptor transcription coactivator activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IDA
Inferred from Direct Assay
more info
PubMed 
transcription corepressor activity IEA
Inferred from Electronic Annotation
more info
 
ubiquitin binding IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin binding TAS
Traceable Author Statement
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
virion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
autophagosome maturation TAS
Traceable Author Statement
more info
PubMed 
cell cycle arrest IEA
Inferred from Electronic Annotation
more info
 
cell division IEA
Inferred from Electronic Annotation
more info
 
endosomal transport TAS
Traceable Author Statement
more info
 
endosome to lysosome transport IEA
Inferred from Electronic Annotation
more info
 
exosomal secretion IEA
Inferred from Electronic Annotation
more info
 
extracellular transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
keratinocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
macroautophagy TAS
Traceable Author Statement
more info
PubMed 
multivesicular body assembly TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of epidermal growth factor receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epidermal growth factor-activated receptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
positive regulation of exosomal secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of nucleic acid-templated transcription IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ubiquitin-dependent endocytosis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of viral budding via host ESCRT complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral release from host cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein monoubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein transport IEA
Inferred from Electronic Annotation
more info
 
regulation of MAP kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cell growth IEA
Inferred from Electronic Annotation
more info
 
regulation of extracellular exosome assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of viral budding via host ESCRT complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
NOT regulation of viral release from host cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IC
Inferred by Curator
more info
PubMed 
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
viral budding IMP
Inferred from Mutant Phenotype
more info
PubMed 
viral budding ISS
Inferred from Sequence or Structural Similarity
more info
 
viral budding via host ESCRT complex TAS
Traceable Author Statement
more info
PubMed 
viral life cycle TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
ESCRT I complex IDA
Inferred from Direct Assay
more info
PubMed 
ESCRT I complex TAS
Traceable Author Statement
more info
PubMed 
Flemming body IEA
Inferred from Electronic Annotation
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol IDA
Inferred from Direct Assay
more info
 
early endosome IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
endosome IDA
Inferred from Direct Assay
more info
PubMed 
endosome membrane TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
late endosome IMP
Inferred from Mutant Phenotype
more info
PubMed 
late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
microtubule organizing center IEA
Inferred from Electronic Annotation
more info
 
multivesicular body TAS
Traceable Author Statement
more info
PubMed 
nucleolus IDA
Inferred from Direct Assay
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
tumor susceptibility gene 101 protein
Names
ESCRT-I complex subunit TSG101
tumor susceptibility gene 10
tumor susceptibility gene 101
tumor susceptibility protein

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_012138.1 RefSeqGene

    Range
    4987..51632
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_006292.3NP_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
    Related
    ENSP00000251968.3, OTTHUMP00000236662, ENST00000251968.3, OTTHUMT00000395906
    Conserved Domains (4) summary
    PHA03369
    Location:93323
    PHA03369; capsid maturational protease; Provisional
    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: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    18480311..18526956 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005253108.4XP_005253165.1  tumor susceptibility gene 101 protein isoform X1

    See identical proteins and their annotated locations for XP_005253165.1

    Conserved Domains (3) summary
    pfam05743
    Location:187
    UEV; UEV domain
    pfam07798
    Location:184240
    DUF1640; Protein of unknown function (DUF1640)
    pfam09454
    Location:264319
    Vps23_core; Vps23 core domain
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