TS101_MOUSE
ID TS101_MOUSE Reviewed; 391 AA.
AC Q61187;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Tumor susceptibility gene 101 protein;
DE AltName: Full=ESCRT-I complex subunit TSG101;
GN Name=Tsg101;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=8616888; DOI=10.1016/s0092-8674(00)81111-3;
RA Li L., Cohen S.N.;
RT "Tsg101: a novel tumor susceptibility gene isolated by controlled
RT homozygous functional knockout of allelic loci in mammalian cells.";
RL Cell 85:319-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ; TISSUE=Mammary gland;
RX PubMed=9840940; DOI=10.1038/sj.onc.1202529;
RA Wagner K.-U., Dierisseau P., Rucker E.B. III, Robinson G.W.,
RA Hennighausen L.;
RT "Genomic architecture and transcriptional activation of the mouse and human
RT tumor susceptibility gene TSG101: common types of shorter transcripts are
RT true alternative splice variants.";
RL Oncogene 17:2761-2770(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Colon, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH DMAP1.
RX PubMed=10888872; DOI=10.1038/77023;
RA Rountree M.R., Bachman K.E., Baylin S.B.;
RT "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at
RT replication foci.";
RL Nat. Genet. 25:269-277(2000).
RN [5]
RP INTERACTION WITH GMCL.
RX PubMed=12927808; DOI=10.1016/s0006-291x(03)01497-9;
RA Masuhara M., Nagao K., Nishikawa M., Kimura T., Nakano T.;
RT "Enhanced degradation of MDM2 by a nuclear envelope component, mouse germ
RT cell-less.";
RL Biochem. Biophys. Res. Commun. 308:927-932(2003).
RN [6]
RP INTERACTION WITH HGS.
RX PubMed=12802020; DOI=10.1073/pnas.0932599100;
RA Lu Q., Hope L.W., Brasch M., Reinhard C., Cohen S.N.;
RT "TSG101 interaction with HRS mediates endosomal trafficking and receptor
RT down-regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7626-7631(2003).
RN [7]
RP INTERACTION WITH MURINE LEUKEMIA VIRUS GAG POLYPROTEIN.
RX PubMed=15908698; DOI=10.1074/jbc.m413735200;
RA Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R., Bertrand E.,
RA Basyuk E.;
RT "Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with
RT Nedd4 ubiquitin ligases during budding.";
RL J. Biol. Chem. 280:27004-27012(2005).
RN [8]
RP INTERACTION WITH MGRN1, AND UBIQUITINATION BY MGRN1.
RX PubMed=19703557; DOI=10.1016/j.bbadis.2009.08.009;
RA Jiao J., Sun K., Walker W.P., Bagher P., Cota C.D., Gunn T.M.;
RT "Abnormal regulation of TSG101 in mice with spongiform neurodegeneration.";
RL Biochim. Biophys. Acta 1792:1027-1035(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Component of the ESCRT-I complex, a regulator of vesicular
CC trafficking process. Binds to ubiquitinated cargo proteins and is
CC required for the sorting of endocytic ubiquitinated cargos into
CC multivesicular bodies (MVBs). Mediates the association between the
CC ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis;
CC the function requires CEP55. May be involved in cell growth and
CC differentiation. Acts as a negative growth regulator. Required for the
CC exosomal release of SDCBP, CD63 and syndecan (By similarity). It may
CC also play a role in the extracellular release of microvesicles that
CC differ from the exosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q99816}.
CC -!- SUBUNIT: Component of the ESCRT-I complex (endosomal sorting complex
CC required for transport I) which consists of TSG101, VPS28, a VPS37
CC protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry.
CC Interacts with VPS37A, VPS37B and VPS37C. Component of an ESCRT-I
CC complex (endosomal sorting complex required for transport I) which
CC consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry.
CC Interacts with DMAP1 (PubMed:10888872). Interacts with GMCL
CC (PubMed:12927808). Interacts with ubiquitin, stathmin and AATF (By
CC similarity). Interacts with HGS; the interaction mediates the
CC association with the ESCRT-0 complex (PubMed:12802020). Interacts with
CC GGA1 and GGA3. Interacts (via UEV domain) with PDCD6IP/AIP1. Interacts
CC with VPS28, SNF8 and VPS36. Self-associates. Interacts with MVB12A; the
CC association appears to be mediated by the TSG101-VPS37 binary
CC subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts
CC with CEP55; the interaction is required for cytokinesis (By
CC similarity). Interacts with PDCD6. Interacts with LITAF (By
CC similarity). Interacts with murine leukemia virus Gag polyprotein (via
CC PSAP motif) (PubMed:15908698). Interacts with MGRN1 (PubMed:19703557).
CC Interacts with ARRDC1; recruits TSG101 to the plasma membrane (By
CC similarity). {ECO:0000250|UniProtKB:Q6IRE4,
CC ECO:0000250|UniProtKB:Q99816, ECO:0000269|PubMed:10888872,
CC ECO:0000269|PubMed:12802020, ECO:0000269|PubMed:12927808,
CC ECO:0000269|PubMed:15908698, ECO:0000269|PubMed:19703557}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99816}. Early
CC endosome membrane {ECO:0000250|UniProtKB:Q99816}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q99816}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q99816}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q99816}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q99816}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q99816}. Midbody,
CC Midbody ring {ECO:0000250|UniProtKB:Q99816}. Nucleus
CC {ECO:0000250|UniProtKB:Q99816}. Note=Mainly cytoplasmic. Membrane-
CC associated when active and soluble when inactive. Nuclear localization
CC is cell cycle-dependent. Interaction with CEP55 is required for
CC localization to the midbody during cytokinesis.
CC {ECO:0000250|UniProtKB:Q99816}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Higher expression in brain and mammary
CC gland. Lower expression in liver and tumoral tissues.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of mammary gland
CC development, but at lower rate at early and mid pregnancy. Expressed in
CC 1-cell and 2-cell stage embryos.
CC -!- DOMAIN: The UEV domain is required for the interaction of the complex
CC with ubiquitin.
CC -!- DOMAIN: The coiled coil domain may interact with stathmin.
CC -!- PTM: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1.
CC Ubiquitination inactivates it, possibly by regulating its shuttling
CC between an active membrane-bound protein and an inactive soluble form.
CC Ubiquitination by MGRN1 requires the presence of UBE2D1.
CC {ECO:0000250|UniProtKB:Q99816}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UEV
CC subfamily. {ECO:0000305}.
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DR EMBL; U52945; AAC53586.1; -; mRNA.
DR EMBL; AF060868; AAC83576.1; -; Genomic_DNA.
DR EMBL; BC005424; AAH05424.1; -; mRNA.
DR EMBL; BC085308; AAH85308.1; -; mRNA.
DR CCDS; CCDS21291.1; -.
DR RefSeq; NP_068684.1; NM_021884.4.
DR AlphaFoldDB; Q61187; -.
DR SMR; Q61187; -.
DR BioGRID; 204341; 53.
DR ELM; Q61187; -.
DR IntAct; Q61187; 24.
DR MINT; Q61187; -.
DR STRING; 10090.ENSMUSP00000014546; -.
DR iPTMnet; Q61187; -.
DR PhosphoSitePlus; Q61187; -.
DR EPD; Q61187; -.
DR jPOST; Q61187; -.
DR MaxQB; Q61187; -.
DR PaxDb; Q61187; -.
DR PRIDE; Q61187; -.
DR ProteomicsDB; 300031; -.
DR Antibodypedia; 1752; 490 antibodies from 40 providers.
DR DNASU; 22088; -.
DR Ensembl; ENSMUST00000014546; ENSMUSP00000014546; ENSMUSG00000014402.
DR GeneID; 22088; -.
DR KEGG; mmu:22088; -.
DR UCSC; uc009gzq.1; mouse.
DR CTD; 7251; -.
DR MGI; MGI:106581; Tsg101.
DR VEuPathDB; HostDB:ENSMUSG00000014402; -.
DR eggNOG; KOG2391; Eukaryota.
DR GeneTree; ENSGT00940000153903; -.
DR HOGENOM; CLU_017548_1_1_1; -.
DR InParanoid; Q61187; -.
DR OMA; YMNFPQP; -.
DR OrthoDB; 1435538at2759; -.
DR PhylomeDB; Q61187; -.
DR TreeFam; TF312917; -.
DR Reactome; R-MMU-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR BioGRID-ORCS; 22088; 28 hits in 80 CRISPR screens.
DR ChiTaRS; Tsg101; mouse.
DR PRO; PR:Q61187; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q61187; protein.
DR Bgee; ENSMUSG00000014402; Expressed in cortical plate and 249 other tissues.
DR ExpressionAtlas; Q61187; baseline and differential.
DR Genevisible; Q61187; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0000813; C:ESCRT I complex; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:MGI.
DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0046790; F:virion binding; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:1990182; P:exosomal secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006858; P:extracellular transport; ISO:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:MGI.
DR GO; GO:2000397; P:positive regulation of ubiquitin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:1903774; P:positive regulation of viral budding via host ESCRT complex; ISO:MGI.
DR GO; GO:0006513; P:protein monoubiquitination; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
DR GO; GO:0001558; P:regulation of cell growth; IDA:MGI.
DR GO; GO:1903551; P:regulation of extracellular exosome assembly; ISO:MGI.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; ISS:UniProtKB.
DR GO; GO:0046755; P:viral budding; IMP:UniProtKB.
DR GO; GO:0019076; P:viral release from host cell; ISO:MGI.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR037202; ESCRT_assembly_dom.
DR InterPro; IPR017916; SB_dom.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR InterPro; IPR008883; UEV_N.
DR Pfam; PF05743; UEV; 1.
DR Pfam; PF09454; Vps23_core; 1.
DR SUPFAM; SSF140111; SSF140111; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS51312; SB; 1.
DR PROSITE; PS51322; UEV; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Cell division; Coiled coil; Cytoplasm;
KW Cytoskeleton; Endosome; Growth regulation; Host-virus interaction;
KW Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q99816"
FT CHAIN 2..391
FT /note="Tumor susceptibility gene 101 protein"
FT /id="PRO_0000082607"
FT DOMAIN 2..145
FT /note="UEV"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00652"
FT DOMAIN 323..391
FT /note="SB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00644"
FT REGION 159..163
FT /note="Interaction with CEP55"
FT /evidence="ECO:0000250"
FT REGION 197..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 237..317
FT /evidence="ECO:0000255"
FT MOTIF 321..324
FT /note="PTAP/PSAP motif"
FT COMPBIAS 200..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q99816"
FT MOD_RES 221
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99816"
SQ SEQUENCE 391 AA; 44124 MW; 79558EC535093492 CRC64;
MAVSESQLKK MMSKYKYRDL TVRQTVNVIA MYKDLKPVLD SYVFNDGSSR ELVNLTGTIP
VRYRGNIYNI PICLWLLDTY PYNPPICFVK PTSSMTIKTG KHVDANGKIY LPYLHDWKHP
RSELLELIQI MIVIFGEEPP VFSRPTVSAS YPPYTATGPP NTSYMPGMPS GISAYPSGYP
PNPSGYPGCP YPPAGPYPAT TSSQYPSQPP VTTVGPSRDG TISEDTIRAS LISAVSDKLR
WRMKEEMDGA QAELNALKRT EEDLKKGHQK LEEMVTRLDQ EVAEVDKNIE LLKKKDEELS
SALEKMENQS ENNDIDEVII PTAPLYKQIL NLYAEENAIE DTIFYLGEAL RRGVIDLDVF
LKHVRLLSRK QFQLRALMQK ARKTAGLSDL Y
