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Protein

Tumor susceptibility gene 101 protein

Gene

TSG101

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426).7 Publications

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • DNA binding Source: ProtInc
  • ligand-dependent nuclear receptor transcription coactivator activity Source: Ensembl
  • protein-containing complex binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transcription corepressor activity Source: ProtInc
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • virion binding Source: UniProtKB

GO - Biological processi

  • autophagosome maturation Source: ParkinsonsUK-UCL
  • cell cycle arrest Source: Ensembl
  • cell division Source: UniProtKB-KW
  • endosomal transport Source: Reactome
  • endosome to lysosome transport Source: Ensembl
  • exosomal secretion Source: Ensembl
  • extracellular transport Source: UniProtKB
  • keratinocyte differentiation Source: Ensembl
  • macroautophagy Source: ParkinsonsUK-UCL
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of cell proliferation Source: Ensembl
  • negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • negative regulation of epidermal growth factor receptor signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of transcription, DNA-templated Source: Ensembl
  • positive regulation of exosomal secretion Source: UniProtKB
  • positive regulation of ubiquitin-dependent endocytosis Source: Ensembl
  • positive regulation of viral budding via host ESCRT complex Source: UniProtKB
  • positive regulation of viral process Source: UniProtKB
  • positive regulation of viral release from host cell Source: UniProtKB
  • protein monoubiquitination Source: Ensembl
  • protein transport Source: UniProtKB-KW
  • regulation of cell growth Source: Ensembl
  • regulation of extracellular exosome assembly Source: UniProtKB
  • regulation of MAP kinase activity Source: UniProtKB
  • regulation of viral budding via host ESCRT complex Source: UniProtKB
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: HGNC
  • viral budding Source: BHF-UCL
  • viral budding via host ESCRT complex Source: ParkinsonsUK-UCL
  • viral life cycle Source: Reactome

Keywordsi

Biological processCell cycle, Cell division, Growth regulation, Host-virus interaction, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-162588 Budding and maturation of HIV virion
R-HSA-174490 Membrane binding and targetting of GAG proteins
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)

Protein family/group databases

MoonDBiQ99816 Curated

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor susceptibility gene 101 protein
Alternative name(s):
ESCRT-I complex subunit TSG101
Gene namesi
Name:TSG101
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000074319.12
HGNCiHGNC:15971 TSG101
MIMi601387 gene
neXtProtiNX_Q99816

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi43V → A: Reduces interaction with ubiquitin; inhibits down-regulation of EGFR. 1 Publication1
Mutagenesisi45N → A: Reduces interaction with ubiquitin. No effect on MGRN1-binding. 3 Publications1
Mutagenesisi46D → A: Reduces interaction with ubiquitin. 1 Publication1
Mutagenesisi63Y → A: Reduces interaction with HIV-1 p6; impairs HIV-1 budding. 1 Publication1
Mutagenesisi88F → A: Reduces interaction with ubiquitin; no effect on in interaction with HIV-1 p6. 1 Publication1
Mutagenesisi89V → A: No change in interaction with p6; no effect on HIV-1 budding. 1 Publication1
Mutagenesisi95M → A: Reduces interaction with VPS37B and HIV-1 p6; abolishes interaction with PDCD6IP; impairs HIV-1 budding; inhibits down-regulation of EGFR. Abolishes MGRN1-binding. Loss of interaction with ARRDC1. 6 Publications1
Mutagenesisi141V → A: Reduces interaction with HIV-1 p6. 1 Publication1
Mutagenesisi158 – 162Missing : Abolishes interaction with CEP55 and midbody localization; no effect on interaction with ESCRT-I proteins, PDCD6IP and viral proteins. 1 Publication5
Mutagenesisi158 – 160PPN → AAA: Abolishes interaction with CEP55. 1 Publication3
Mutagenesisi368 – 371RKQF → AAAA: Loss of interaction with VPS28. No effect on interaction with VPS37C. 1 Publication4

Organism-specific databases

DisGeNETi7251
MalaCardsiTSG101
OpenTargetsiENSG00000074319
PharmGKBiPA38068

Chemistry databases

ChEMBLiCHEMBL6157

Polymorphism and mutation databases

BioMutaiTSG101
DMDMi9789790

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000826062 – 390Tumor susceptibility gene 101 proteinAdd BLAST389

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei220PhosphothreonineCombined sources1

Post-translational modificationi

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 UBE2D1.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99816
MaxQBiQ99816
PaxDbiQ99816
PeptideAtlasiQ99816
PRIDEiQ99816
ProteomicsDBi78490
78491 [Q99816-2]

PTM databases

iPTMnetiQ99816
PhosphoSitePlusiQ99816

Expressioni

Tissue specificityi

Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.

Gene expression databases

BgeeiENSG00000074319
CleanExiHS_TSG101
ExpressionAtlasiQ99816 baseline and differential
GenevisibleiQ99816 HS

Organism-specific databases

HPAiCAB004283
HPA006161

Interactioni

Subunit structurei

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 MVB12A or MVB12B in a 1:1:1:1 stoichiometry (PubMed:18005716). Interacts with VPS37A, VPS37B and VPS37C (PubMed:15218037, PubMed:15509564). Interacts with DMAP1 (PubMed:10888872). Interacts with ubiquitin (PubMed:11595185). Interacts with stathmin, GMCL and AATF (By similarity). Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry (PubMed:21757351). Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex. Interacts with GGA1 and GGA3 (PubMed:15143060, PubMed:15039775). Interacts (via UEV domain) with PDCD6IP/AIP1 (PubMed:14505570, PubMed:14519844). Interacts with VPS28, SNF8 and VPS36 (PubMed:14505570). Self-associates (PubMed:14505570, PubMed:14519844). Interacts with 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 (PubMed:17853893). Interacts with PDCD6 (PubMed:18256029). Interacts with LITAF (PubMed:23166352). Interacts with MGRN1 (PubMed:17229889). Interacts with ARRDC1; recruits TSG101 to the plasma membrane (PubMed:21191027, PubMed:22315426).By similarity19 Publications
(Microbial infection) Interacts with HIV-1 p6.5 Publications
(Microbial infection) Interacts with human spumavirus Gag.1 Publication
(Microbial infection) Interacts with HTLV-1 Gag.1 Publication
(Microbial infection) Interacts with Ebola virus VP40.1 Publication
(Microbial infection) Interacts with EIAV p9; the interaction has been shown in vitro.1 Publication
(Microbial infection) Interacts with Lassa virus protein Z.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113102, 174 interactors
CORUMiQ99816
DIPiDIP-31809N
ELMiQ99816
IntActiQ99816, 137 interactors
MINTiQ99816
STRINGi9606.ENSP00000251968

Chemistry databases

BindingDBiQ99816

Structurei

Secondary structure

1390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 11Combined sources7
Turni12 – 14Combined sources3
Helixi18 – 31Combined sources14
Beta strandi35 – 42Combined sources8
Turni47 – 49Combined sources3
Beta strandi51 – 62Combined sources12
Beta strandi67 – 75Combined sources9
Turni78 – 82Combined sources5
Beta strandi86 – 89Combined sources4
Beta strandi95 – 97Combined sources3
Beta strandi100 – 103Combined sources4
Beta strandi107 – 109Combined sources3
Helixi112 – 115Combined sources4
Turni119 – 121Combined sources3
Helixi124 – 137Combined sources14
Beta strandi140 – 143Combined sources4
Helixi230 – 299Combined sources70

3D structure databases

ProteinModelPortaliQ99816
SMRiQ99816
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99816

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 145UEVPROSITE-ProRule annotationAdd BLAST144
Domaini322 – 390SBPROSITE-ProRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni158 – 162Interaction with CEP555

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili235 – 316Sequence analysisAdd BLAST82

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi320 – 323PTAP motif4

Domaini

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.
The coiled coil domain may interact with stathmin.
The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently.

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2391 Eukaryota
ENOG410XT2Q LUCA
GeneTreeiENSGT00530000064004
HOGENOMiHOG000247008
HOVERGENiHBG057450
InParanoidiQ99816
KOiK12183
OMAiDHNGKVY
OrthoDBiEOG091G0HRA
PhylomeDBiQ99816
TreeFamiTF312917

Family and domain databases

Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR037202 ESCRT_assembly_dom
IPR017916 SB_dom
IPR016135 UBQ-conjugating_enzyme/RWD
IPR008883 UEV_N
PfamiView protein in Pfam
PF05743 UEV, 1 hit
PF09454 Vps23_core, 1 hit
SUPFAMiSSF140111 SSF140111, 1 hit
SSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS51312 SB, 1 hit
PS51322 UEV, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Several shorter isoforms are detected in primary breast cancers and other tumors.
Isoform 1 (identifier: Q99816-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVSESQLKK MVSKYKYRDL TVRETVNVIT LYKDLKPVLD SYVFNDGSSR
60 70 80 90 100
ELMNLTGTIP VPYRGNTYNI PICLWLLDTY PYNPPICFVK PTSSMTIKTG
110 120 130 140 150
KHVDANGKIY LPYLHEWKHP QSDLLGLIQV MIVVFGDEPP VFSRPISASY
160 170 180 190 200
PPYQATGPPN TSYMPGMPGG ISPYPSGYPP NPSGYPGCPY PPGGPYPATT
210 220 230 240 250
SSQYPSQPPV TTVGPSRDGT ISEDTIRASL ISAVSDKLRW RMKEEMDRAQ
260 270 280 290 300
AELNALKRTE EDLKKGHQKL EEMVTRLDQE VAEVDKNIEL LKKKDEELSS
310 320 330 340 350
ALEKMENQSE NNDIDEVIIP TAPLYKQILN LYAEENAIED TIFYLGEALR
360 370 380 390
RGVIDLDVFL KHVRLLSRKQ FQLRALMQKA RKTAGLSDLY
Length:390
Mass (Da):43,944
Last modified:August 1, 1998 - v2
Checksum:iADD6912FC22DF162
GO
Isoform 2 (identifier: Q99816-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     15-119: Missing.

Note: Detected in normal as well as cancer tissues.
Show »
Length:285
Mass (Da):31,732
Checksum:i035C70BEC887273D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti343F → L in AAH02487 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034572167M → I. Corresponds to variant dbSNP:rs34385327Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00444015 – 119Missing in isoform 2. CuratedAdd BLAST105

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82130 mRNA Translation: AAC52083.1
BC002487 mRNA Translation: AAH02487.1
CCDSiCCDS7842.1 [Q99816-1]
RefSeqiNP_006283.1, NM_006292.3 [Q99816-1]
UniGeneiHs.523512

Genome annotation databases

EnsembliENST00000251968; ENSP00000251968; ENSG00000074319 [Q99816-1]
GeneIDi7251
KEGGihsa:7251
UCSCiuc001mor.4 human [Q99816-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTS101_HUMAN
AccessioniPrimary (citable) accession number: Q99816
Secondary accession number(s): Q9BUM5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 1, 1998
Last modified: July 18, 2018
This is version 205 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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