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Vacuolar protein sorting-associated protein: Difference between revisions

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<StructureSection load='3q66' size='400' side='right' caption='Vps75 (deepskyblue and green) complex with histone acetyltransferase (magenta) and sulfate (PDB code [[3q68]])' scene='80/803271/Cv/4'>
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>


== Function ==
== Function ==


'''Vacuolar protein sorting-associated protein''' (Vps) are part of '''E'''ndosomal '''S'''orting '''C'''omplex '''R'''equired for '''T'''ransport ('''ESCRT''') that performs the topologically unique membrane bending and scission reaction away from the cytoplasm.  This process is required for the multivesicular body pathway, cytokinesis and HIV budding.  There are five distinct ESCRT complexes (0,I,II,III,Vps4) with distinct functions<ref>PMID:22361144</ref>.
'''Vacuolar protein sorting-associated protein''' (Vps) are part of '''E'''ndosomal '''S'''orting '''C'''omplex '''R'''equired for '''T'''ransport ('''ESCRT''') that performs the topologically unique membrane bending and scission reaction away from the cytoplasm.  This process is required for the multivesicular body (MVP) pathway, cytokinesis and HIV budding.  There are five distinct ESCRT complexes (0,I,II,III,Vps4) with distinct functions<ref>PMID:22361144</ref>. The '''retromer''' comprises 2 functional subcomplexes: the cargo-selective one which contains Vps35, Vps29 and Vps26 and the sorting nexin subcomplex which tubulate the endosomal membrane<ref>PMID:19531583</ref>. The Vps proteins are found in yeast.  The human homologs are called also '''chromatin-modifying protein''' or [[Charged multivesicular body protein]] ('''CHMP''')<ref>PMID:16730941</ref>.
*'''Vps4''', '''Vps4A''', ''Vps4B'' complex catalyzes the disassembly of the ESCRT-III filament in an ATP-driven reaction.  Vps4 proteins are required for centrosome and spindle maintenance<ref>PMID:20616062</ref>.<br />
*'''Vps9A''' activates Rab5 to GTP-bound form<ref>PMID:18055610</ref>.<br />
*'''Vps15''' may function as a G protein β subunit at the endosome <ref>PMID:19445518</ref>.<br />
*'''Vps23''' is involved in appropriate sorting of receptors within the yast endocytic pathway and is part of the ESCRT-I complex<ref>PMID:11134028</ref><br />
*'''Vps25''' is part of the ESCRT-II complex which contains two copies of the protein.  It induces a conformational switch that converts inactive Vps20 into an active nucleator for Snf7 oligomerization<ref>PMID:20134403</ref>.<br />
*'''Vps26A''' and '''Vps26B''' are part of the '''Vps29'''-'''Vps35'''-Vps26 retromer which mediates transport of transmembrane proteins from endosomes to the trans-Golgi network<ref>PMID:21920005</ref>.<br />
*'''Vps27''' interacts with the lipid phosphatidylinositol-3-phosphate and this interaction activates the MVP sorting pathway.  Vps27 is part of the ESCRT-I complex<ref>PMID:12900393</ref>.<br />
*'''Vps28''' C-terminal links ESCRT-I and ESCRT-II<ref>PMID:17215868</ref>.<br />
*'''Vps29''', '''Vps30''' and '''Vps35''' are required for the recycling of Vps10p from the prevacuolar endosome back to the Golgi<ref>PMID:9105038</ref>.<br />
*'''Vps33''' binds SNARE domains<ref>PMID:23051737</ref>.<br />
*'''Vps33A''' is part of the homotypic fusion and vacuole sorting comples which is required for fusion of intracellular compartments with lysosomes<ref>PMID:25783203</ref>.<br />
*'''Vps34''' is a class III [[Phosphoinositide 3-Kinases]]<ref>PMID:21835792</ref>.<br />
*'''Vps36''' contains a ubiquitin-binding domain and is required for vacuolar sorting of ubiqinated membrane proteins.  Vps36 is part of the ESCRT-II complex<ref>PMID:15755741</ref>.<br />
*'''Vps46''' is part of the ESCRT-II complex<ref>PMID:29046462</ref>.<br />
*'''Vps53''' C-terminal is important for binding endosome-derived vesicles<ref>PMID:20660722</ref>.<br />
*'''Vps54''' is part of the Golgi-associated retrograde protein complex (GARP) of vesicle sorting proteins<ref>PMID:18574757</ref>.<br />
*'''Vps60''' is involved in filament maturation<ref>PMID:12940986</ref>.<br />
*'''Vps74''' is a sensor of phosphatidylinositol 4-kinase level on medial Golgi cisternae<ref>PMID:22553372</ref>.<br />
*'''Vps75''' is a histone chaperone which functions in chromatin assembly and disassembly<ref>PMID:23401858</ref>.<br />
*'''Vps Vta1''' is a cofactor ov Vps4<ref>PMID:20696398</ref>.<br />


== Disease ==
== Disease ==
Mutations in '''Vps53''' cause progressive cerebello-cerebral atrophy type 2<ref>PMID:24577744</ref>.  Mutations in '''Vps54''' in mice cause motor neuron disease<ref>PMID:16244655</ref>. Dysfunction of the '''retromer''' is implicated in neurodegenerative disease like Alzheimer disease, Parkinson's disease and Frontotemporal lobar degeneration<ref>PMID:29755290</ref>.


== Relevance ==
== Relevance ==


Vps25 in ''Drosophila'' possesses several properties of tumor repressor<ref>PMID:16256745</ref>.  Vps36 is downregulated in advanced prostate cancer<ref>PMID:28197629</ref>.
*Vps26A
== Structural highlights ==
== Structural highlights ==


 
Vps75 interacts with histone acetyltransferase through three interfacing areas. <scene name='80/803271/Cv/12'>The main interface area contains a globular motif that surrounds Vps75 Leu223 and several hydrogen bonds and salt bridges</scene>. The other two interfaces are on each side of the catalytic enclosure and contain hydrophobic contacts and salt bridges<ref>PMID:21454705</ref>.
*<scene name='80/803271/Cv/13'>2nd interface</scene>.
*<scene name='80/803271/Cv/14'>3rd interface</scene>.
==3D structures of vacuolar protein sorting-associated protein==
[[Vacuolar protein sorting-associated protein 3D structures]]
</StructureSection>
</StructureSection>


==3D structures of vacuolar protein sorting-associated protein==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
*Vps4
**[[5xmi]] – yVps4 + ATP – yeast - Cryo EM<br />
**[[2rko]] – yVps4 AAA ATPase domain 124-437<br />
**[[3eie]] – yVps4 AAA ATPase domain (mutant) 124-437<br />
**[[3eih]] – yVps4 AAA ATPase domain (mutant) 124-437 + ATPgS<br />
**[[2qp9]] – yVps4 83-437<br />
**[[2qpa]] – yVps4 (mutant) 83-437 + ADP<br />
**[[2v6x]] – yVps4 MIT domain 1-82 + yVps2 C-terminal<br />
**[[4niq]], [[5fvk]] – yVps4 MIT domain + yVfa1 MIM2 domain<br />
**[[5fvl]] – yVps4 MIT domain + yVPS20 <br />
**[[3mhv]] – yVps4 + yVps Vta1 <br />
**[[6ap1]] – yVps4 + yVps Vta1 + peptide<br />
**[[5uie]] – yVps4 + yVps2 + yVps Vta1 – Cryo EM<br />
**[[5xmk]] – yVps4 + yVps Vta1 + ATP – Cryo EM<br />
**[[6bmf]] – yVps4 AAA ATPase domain + yVps2P – Cryo EM<br />
*Vps4A
**[[1yxr]] – hVps4A MIT domain – human - NMR<br />
**[[2jq9]] – hVps4A MIT domain + CHMP1A peptide - NMR<br />
**[[2k3w]] – yVps4A MIT domain + CHMP6 peptide - NMR<br />
*Vps4B or Skd1
**[[2jqh]], [[2cpt]], [[1wr0]] – hVps4B MIT domain - NMR<br />
**[[1xwi]] – hVps4B C-terminal<br />
**[[4u7y]] – hVps4B MIT domain + IST1 peptide<br />
**[[2jqk]] – hVps4B MIT domain + CHMP2B<br />
**[[2zam]] – mVps4B - mouse<br />
**[[2zao]] – mVps4B + ADP<br />
**[[2zan]] – mVps4B + ATP<br />
*Vps9
**[[1mn3]] – yVps9 CUE domain 398-451<br />
**[[1p3q]] – yVps9 CUE domain + ubiquitin<br />
*Vps9A
**[[4g01]] – Vps9A + RABF2B – ''Arabidopsis thaliana''<br />
*Vps13
**[[6cbc]] – CtVps13 N-terminal (mutant) – ''Chaetomium thermophilum'' <br />
*Vps15 or serine/threonine protein kinase Vps15
**[[3gre]] – yVps15 WD repeat domain <br />
*Vps23
**[[2f6m]] – yVps23 C-terminal (mutant) + yVps28 N-terminal<br />
**[[3r42]] – yVps23 N-terminal (mutant) + yVps27 peptide <br />
**[[2caz]] – yVps23 + yVps28 N-terminal + SRN2 <br />
**[[2f66]] – yVps23 C-terminal + yVps28 N-terminal + SRN2<br />
**[[2p22]] – yVps23 + yVps28 N-terminal + SRN2 + peptide  <br />
**[[1uzx]] – yVps23 UEV domain 1-161 + ubiquitin <br />
*Vps25
**[[3htu]] – hVps23 C-terminal WH2 domain + hVps20 first helix <br />
*Vps26A
**[[6md5]] – Vps26A – zebrafish<br />
**[[4p2a]] – mVps26A + sorting nexin-3 <br />
*Vps26B
**[[3lh8]], [[2r51]] – mVps26B <br />
**[[3lh9]], [[3lha]] – mVps26B (mutant)<br />
*Vps27
**[[2pjw]] – yVps27 C-terminal + protein<br />
*Vps28
**[[2g3q]], [[2j9v]] – yVps28 C-terminal <br />
**[[2j9u]] – yVps28 + yVps36 <br />
*Vps29
**[[3psn]], [[3pso]] – mVps29 <br />
**[[5w8m]] – CtVps29  <br />
**[[6h7w]] – CtVps29 + CtVps35 + CtVps26-like + CtVPS - Cryo EM<br />
**[[2r17]] – yVps29 + yVps35 <br />
**[[5wyh]] – hVps29 + interaptin<br />
**[[5osh]], [[5osi]] – hVps29 + hVps35 + interaptin<br />
**[[5gtu]] – hVps29 + TBC1D5<br />
**[[5xce]], [[5xch]] – EhVps29 – ''Entamoeba histolytica'' <br />
**[[5xcj]], [[5xck]] – EhVps29 (mutant)<br />
*Vps30
**[[3vp7]] – hVps30 C-terminal <br />
*Vps33
**[[5bv1]] – CtVps33 + CtVps16 <br />
**[[5bv0]] – CtVps33 + CtVps16 <br />
*Vps33A
**[[4bx8]] – hVps33A <br />
**[[4bx9]] – hVps33A + hVps16 C-terminal + SNARE domain<br />
*Vps34
**[[5dfz]] – yVps34 + yVps38 + yVps15 + yVps30 + nanobody<br />
*Vps35
**[[5f0k]] – hVps35 N-terminal <br />
**[[5f0j]] – hVps35 + hVps26A + sorting nexin-3 <br />
**[[5f0l]], [[5f0m]], [[5f0p]] – hVps35 + hVps26A + sorting nexin-3 + DMT-1<br />
*Vps36
**[[5kc2]] – yVps36 + yVps15 <br />
**[[2hth]] – hVps36 GLUE domain 1-138 + ubiquitin <br />
**[[2zme]], [[3cuq]] – hVps36 + hVps25 + SNF8 <br />
*Vps46
**[[3ggz]] – yVps46 MIM motif 176-204 + IST1 <br />
*Vps53
**[[3ns4]] – yVps53 C-terminal <br />
*Vps54
**[[3n1b]] – yVps54 C-terminal <br />
**[[3n1e]] – mVps54 C-terminal <br />
*Vps60
**[[2luh]] – yVps60 + yVps Vta1 - NMR <br />
*Vps72
**[[6gej]], [[6gen]] – yVps72 + histones H3 + H4 + H2A.1 + H2B.1 + DNA + Swr1 + Arp6 + RuvbL1 + RuvbL2 + Swr complex protein 6 – Cryo EM<br />
*Vps72 homolog
**[[5chl]] – Vps72 + histone H2A.Z – ''Drosophila melanogaster'' <br />
**[[5fug]] – hVps72 N-terminal + histone H2A.Z <br />
*Vps74
**[[2zih]], [[2zii]] – yVps74<br />
**[[4tu3]] – yVps74 + SAC1<br />
*Vps75
**[[3c9b]], [[3c9d]], [[5agc]] – yVps75 <br />
**[[3dm7]] – yVps75 (mutant)<br />
**[[2zd7]] – yVps75 + peptide  <br />
**[[3q68]], [[3q66]] – yVps75 + histone acetyltransferase  <br />
**[[3q33]] – yVps75 + histone acetyltransferase + histone H3 peptide <br />
**[[3q35]] – yVps75 + histone acetyltransferase + acetyl CoA<br />
**[[5yps]] – Vps75 (mutant) – Pneumocystis carinii<br />
*Vps Vta1 or Lip5
**[[2lxl]] – hVps Vta1 <br />
**[[4txp]] – hVps Vta1 N-terminal <br />
**[[2rkk]] – yVps Vta1 N-terminal <br />
**[[2rkl]] – yVps Vta1 C-terminal <br />
**[[5h7p]] – yVps Vta1 N-terminal + yVps46 D1-D2 domain - NMR<br />
**[[4u7e]] – hVps Vta1 N-terminal + IST1<br />
**[[2lxm]] – hVps Vta1 N-terminal + CHMP5<br />
**[[4txq]] – hVps Vta1 N-terminal + CHMP1B<br />
**[[4txr]] – hVps Vta1 N-terminal + CHMP1B + CHMP5<br />
}}
== References ==
== References ==
<references/>
<references/>


[[Category:Topic Page]]
[[Category:Topic Page]]

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Michal Harel, Alexander Berchansky
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