Endosomal sorting complex required for transport (Homo sapiens)

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3, 4, 712, 61, 85, 9endosome membranecytosolUBB(153-228) UBC(229-304) VPS37D UBC(609-684) ESCRT-III/CargoComplexUBB(1-76) UBA52(1-76) VPS25 VPS37C ATPCHMP4B UBC(153-228) VPS37A ESCRT-II/CargoComplexCHMP2A UBB(77-152) UBC(533-608) ESCRT-IIIUBC(1-76) UBC(77-152) UBC(609-684) UBC(457-532) UBC(457-532) UBC(381-456) VPS37A SNF8 UBC(305-380) UBC(153-228) CHMP4UBB(153-228) TSG101 STAM2 UBB(1-76) HGS UBC(1-76) VPS36 CHMP4B CHMP4B STAM2 ESCRT-ICHMP2B RPS27A(1-76) VPS37C CHMP4A UBC(533-608) UBB(77-152) PI(3,4,5)P3 UBC(305-380) PI(3,4,5)P3 UBC(77-152) UBC(1-76) RPS27A(1-76) UBA52(1-76) CHMP3 UBC(77-152) VPS37B VPS37B UBC(609-684) STAM CHMP6 CHMP4C UBC(533-608) CHMP4A VPS28 ESCRT-IIUBC(1-76) UBC(381-456) RPS27A(1-76) UBA52(1-76) UBC(381-456) VPS25 CHMP2A CHMP7 TSG101 UBC(153-228) UBC(77-152) Ubiquinated and PIP3Endosmal MembraneBound CargoCHMP4C PI(3,4,5)P3 ESCRT-0/CargoComplexUBC(457-532) ESCRT-0UBB(153-228) PI(3,4,5)P3 CHMP6 CHMP3 VPS4B UBA52(1-76) CHMP4C CHMP3ADPCHMP2CHMP4A UBC(77-152) UBC(229-304) CHMP7 VPS28 UBB(77-152) UBB(153-228) UBC(533-608) CHMP7UBC(609-684) RPS27A(1-76) CHMP5 HGS VPS4A UBC(1-76) CHMP2B UBC(229-304) UBC(457-532) Vps/Vta1UBC(533-608) UBC(457-532) RPS27A(1-76) VTA1 UBC(381-456) CHMP2B UBB(153-228) CHMP6UBC(609-684) UBC(305-380) UBC(381-456) VPS37D STAM SNF8 UBC(153-228) VPS36 UBC(305-380) UBC(229-304) UBB(77-152) UBB(1-76) UBC(229-304) UBB(1-76) UBB(77-152) UBB(1-76) ESCRT-I/CargoComplexCHMP2A PI(3,4,5)P3 UBC(305-380) UBC(153-228) PiUBA52(1-76)


Description

Many 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 the cell surface. Others are sorted into intralumenal vesicles of morphologically distinctive endosomes that are known as multivesicular bodies (MVBs). These MVBs fuse with lysosomes, resulting in degradation of their cargo by lysosomal acidic hydrolases.

Endosomes can be operationally defined as being either early or late, referring to the relative time it takes for endocytosed material to reach either stage. Ultrastructural studies indicate that early endosomes are predominantly tubulovesicular structures, which constitute a major sorting platform in the cell, whereas late endosomes show the characteristics of typical MVBs and are capable of fusing with lysosomes.

A well characterized signal for shunting membrane proteins into the degradative MVB pathway is the ubiquitylation of these cargoes. At the center of a vast protein:protein and protein:lipid interaction network that underpins ubiquitin mediated sorting to the lysosome are the endosomal sorting complexes required for transport (ESCRTs), which are conserved throughout all major eukaryotic taxa.

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Bibliography

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  1. Clague MJ, Urbé S.; ''Hrs function: viruses provide the clue.''; PubMed Europe PMC Scholia
  2. Teis D, Saksena S, Emr SD.; ''SnapShot: the ESCRT machinery.''; PubMed Europe PMC Scholia
  3. Stuchell MD, Garrus JE, Müller B, Stray KM, Ghaffarian S, McKinnon R, Kräusslich HG, Morham SG, Sundquist WI.; ''The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding.''; PubMed Europe PMC Scholia
  4. Saksena S, Sun J, Chu T, Emr SD.; ''ESCRTing proteins in the endocytic pathway.''; PubMed Europe PMC Scholia
  5. Langelier C, von Schwedler UK, Fisher RD, De Domenico I, White PL, Hill CP, Kaplan J, Ward D, Sundquist WI.; ''Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release.''; PubMed Europe PMC Scholia
  6. Morita E, Sandrin V, Alam SL, Eckert DM, Gygi SP, Sundquist WI.; ''Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.''; PubMed Europe PMC Scholia
  7. Stefani F, Zhang L, Taylor S, Donovan J, Rollinson S, Doyotte A, Brownhill K, Bennion J, Pickering-Brown S, Woodman P.; ''UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.''; PubMed Europe PMC Scholia
  8. Williams RL, Urbé S.; ''The emerging shape of the ESCRT machinery.''; PubMed Europe PMC Scholia
  9. Bowers K, Piper SC, Edeling MA, Gray SR, Owen DJ, Lehner PJ, Luzio JP.; ''Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII.''; PubMed Europe PMC Scholia
  10. Sachse M, Strous GJ, Klumperman J.; ''ATPase-deficient hVPS4 impairs formation of internal endosomal vesicles and stabilizes bilayered clathrin coats on endosomal vacuoles.''; PubMed Europe PMC Scholia
  11. de Souza RF, Aravind L.; ''UMA and MABP domains throw light on receptor endocytosis and selection of endosomal cargoes.''; PubMed Europe PMC Scholia
  12. Scheuring S, Röhricht RA, Schöning-Burkhardt B, Beyer A, Müller S, Abts HF, Köhrer K.; ''Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking.''; PubMed Europe PMC Scholia
  13. Agromayor M, Soler N, Caballe A, Kueck T, Freund SM, Allen MD, Bycroft M, Perisic O, Ye Y, McDonald B, Scheel H, Hofmann K, Neil SJ, Martin-Serrano J, Williams RL.; ''The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
123637view09:43, 7 August 2022EgonwModified title
117709view12:27, 22 May 2021EweitzModified title
114641view16:10, 25 January 2021ReactomeTeamReactome version 75
113089view11:15, 2 November 2020ReactomeTeamReactome version 74
112323view15:24, 9 October 2020ReactomeTeamReactome version 73
101222view11:11, 1 November 2018ReactomeTeamreactome version 66
100760view20:37, 31 October 2018ReactomeTeamreactome version 65
100304view19:14, 31 October 2018ReactomeTeamreactome version 64
99851view15:58, 31 October 2018ReactomeTeamreactome version 63
99408view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99097view12:39, 31 October 2018ReactomeTeamreactome version 62
93961view13:48, 16 August 2017ReactomeTeamreactome version 61
93557view11:27, 9 August 2017ReactomeTeamreactome version 61
87437view13:37, 22 July 2016MkutmonOntology Term : 'transport pathway' added !
86660view09:23, 11 July 2016ReactomeTeamreactome version 56
83465view12:29, 18 November 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CHMP2A ProteinO43633 (Uniprot-TrEMBL)
CHMP2B ProteinQ9UQN3 (Uniprot-TrEMBL)
CHMP2ComplexR-HSA-917705 (Reactome)
CHMP3 ProteinQ9Y3E7 (Uniprot-TrEMBL)
CHMP3ProteinQ9Y3E7 (Uniprot-TrEMBL)
CHMP4A ProteinQ9BY43 (Uniprot-TrEMBL)
CHMP4B ProteinQ9H444 (Uniprot-TrEMBL)
CHMP4C ProteinQ96CF2 (Uniprot-TrEMBL)
CHMP4ComplexR-HSA-917714 (Reactome)
CHMP5 ProteinQ9NZZ3 (Uniprot-TrEMBL)
CHMP6 ProteinQ96FZ7 (Uniprot-TrEMBL)
CHMP6ProteinQ96FZ7 (Uniprot-TrEMBL)
CHMP7 ProteinQ8WUX9 (Uniprot-TrEMBL)
CHMP7ProteinQ8WUX9 (Uniprot-TrEMBL)
ESCRT-0/Cargo ComplexComplexR-HSA-917704 (Reactome)
ESCRT-0ComplexR-HSA-917726 (Reactome)
ESCRT-I/Cargo ComplexComplexR-HSA-917702 (Reactome)
ESCRT-II/Cargo ComplexComplexR-HSA-917698 (Reactome)
ESCRT-III/Cargo ComplexComplexR-HSA-917699 (Reactome)
ESCRT-IIIComplexR-HSA-917723 (Reactome)
ESCRT-IIComplexR-HSA-917707 (Reactome)
ESCRT-IComplexR-HSA-184398 (Reactome)
HGS ProteinO14964 (Uniprot-TrEMBL)
PI(3,4,5)P3 MetaboliteCHEBI:16618 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SNF8 ProteinQ96H20 (Uniprot-TrEMBL)
STAM ProteinQ92783 (Uniprot-TrEMBL)
STAM2 ProteinO75886 (Uniprot-TrEMBL)
TSG101 ProteinQ99816 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ubiquinated and PIP3

Endosmal Membrane

Bound Cargo		ComplexR-HSA-917712 (Reactome)
VPS25 ProteinQ9BRG1 (Uniprot-TrEMBL)
VPS28 ProteinQ9UK41 (Uniprot-TrEMBL)
VPS36 ProteinQ86VN1 (Uniprot-TrEMBL)
VPS37A ProteinQ8NEZ2 (Uniprot-TrEMBL)
VPS37B ProteinQ9H9H4 (Uniprot-TrEMBL)
VPS37C ProteinA5D8V6 (Uniprot-TrEMBL)
VPS37D ProteinQ86XT2 (Uniprot-TrEMBL)
VPS4A ProteinQ9UN37 (Uniprot-TrEMBL)
VPS4B ProteinO75351 (Uniprot-TrEMBL)
VTA1 ProteinQ9NP79 (Uniprot-TrEMBL)
Vps/Vta1ComplexR-HSA-917724 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-917693 (Reactome)
ATPR-HSA-917693 (Reactome)
CHMP2ArrowR-HSA-917693 (Reactome)
CHMP3ArrowR-HSA-917693 (Reactome)
CHMP4ArrowR-HSA-917693 (Reactome)
CHMP6ArrowR-HSA-917693 (Reactome)
CHMP7ArrowR-HSA-917693 (Reactome)
ESCRT-0/Cargo ComplexR-HSA-917730 (Reactome)
ESCRT-0ArrowR-HSA-917730 (Reactome)
ESCRT-I/Cargo ComplexArrowR-HSA-917730 (Reactome)
ESCRT-I/Cargo ComplexR-HSA-917696 (Reactome)
ESCRT-IArrowR-HSA-917696 (Reactome)
ESCRT-II/Cargo ComplexArrowR-HSA-917696 (Reactome)
ESCRT-II/Cargo ComplexR-HSA-917700 (Reactome)
ESCRT-IIArrowR-HSA-917700 (Reactome)
ESCRT-III/Cargo ComplexArrowR-HSA-917700 (Reactome)
ESCRT-III/Cargo ComplexR-HSA-917693 (Reactome)
ESCRT-IIIR-HSA-917700 (Reactome)
ESCRT-IIR-HSA-917696 (Reactome)
ESCRT-IR-HSA-917730 (Reactome)
PiArrowR-HSA-917693 (Reactome)
R-HSA-917693 (Reactome) Disassembly Phase
The AAA-ATPase, Vps4 disassembles ESCRT-III and catalyzes the final step of the MVB pathway. The microtubule interacting and trafficking (MIT) domain of Vps4 interacts directly with the C-terminal region of Vps2 (MIM1) and Vps20 (MIM2). The association of Vta1, which contains two MIT domains, greatly enhances the activity of Vps4. Please note that the recomended names of the Vacuolar protein sorting-associated proteins (Vps) are Charged multivesicular body proteins or CHMPs.
R-HSA-917696 (Reactome) ESCRT-0 recruits ESCRT-I and thereby initiates the MVB pathway. Cargo Sorting ESCRT-I is a heterotetramer consisting of Vps23, Vps28, Vps37, and Mvb12. The UEV domain of Vps23 binds ubiquitinated membrane proteins. Vps28 interacts with the GLUE domain of Vps36 in ESCRT-II. Cargo Sorting ESCRT-II is a heterotetramer formed of Vps36, Vps22, and two Vps25 molecules. The GLUE domain of Vps36 binds PI3P, Vps28, and ubiquitinated membrane proteins. Vps25 interacts with Vps20 of ESCRT-III.
R-HSA-917700 (Reactome) ESCRT-III assembles into a highly ordered filament-like hetero-oligomer. Vps20 nucleates the homo-oligomerization of Snf7 that is capped by Vps24. Vps24 recruits Vps2 and initiates Vps4-dependent ESCRT-III disassembly. ESCRT-III is required for the last steps of MVB sorting, cargo sequestration, and MVB vesicle formation.
R-HSA-917730 (Reactome) Initiation/Cargo Recognition is mediated by ESCRT-0, a heterodimer consisting of Vps27 and Hse1. ESCRT-0 binds Phosphatidyl inositol 3- phosphate (PI3P) on endosomes via a FVYE domain and ubiquitinated cargo via two UIM domains.
Ubiquinated and PIP3

Endosmal Membrane

Bound Cargo		ArrowR-HSA-917693 (Reactome)
Vps/Vta1mim-catalysisR-HSA-917693 (Reactome)
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