P46467
PR
Gene name |
Vps4b |
Protein name |
Vacuolar protein sorting-associated protein 4B |
Names |
Suppressor of K(+) transport growth defect 1, Protein SKD1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:20479 |
EC number |
3.6.4.6: Acting on ATP; involved in cellular and subcellular movement |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with Q9UN37)
VPS4 proteins are AAA+ ATPases required to form multivesicular bodies, release viral particles, and complete cytokinesis. VPS4 proteins act by disassembling ESCRT-III heteropolymers during or after their proposed function in membrane scission. Deleting the N-terminal MIT domain and adjacent linker from VPS4A increases both basal and liposome-enhanced ATPase activity, indicating that these elements play a role in autoinhibiting VPS4A until it encounters ESCRT-III polymers. The interactions between acidic ESCRT-III residues and sequences in VPS4A, in particular in the linker connecting the MIT and AAA+ domains, are involved in regulating the intrinsic autoinhibition of the enzyme.
Autoinhibitory domains (AIDs)
Target domain |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
4 structures for P46467
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2ZAM | X-ray | 350 A | A | 1-444 | PDB |
| 2ZAN | X-ray | 300 A | A | 1-444 | PDB |
| 2ZAO | X-ray | 320 A | A | 1-444 | PDB |
| AF-P46467-F1 | Predicted | AlphaFoldDB |
18 variants for P46467
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3390387568 | 95 | V>L | No | EVA | |
| rs3388494369 | 114 | K>R | No | EVA | |
| rs3388493297 | 155 | K>R | No | EVA | |
| rs3390422459 | 164 | R>L | No | EVA | |
| rs3388492640 | 180 | K>E | No | EVA | |
| rs13459431 | 186 | A>V | No | EVA | |
| rs13459432 | 190 | E>K | No | EVA | |
| rs3388492493 | 249 | E>Q | No | EVA | |
| rs3388494361 | 251 | A>V | No | EVA | |
| rs3413127645 | 273 | L>W | No | EVA | |
| rs3388493125 | 288 | I>F | No | EVA | |
| rs3390422934 | 314 | L>S | No | EVA | |
| rs3388491484 | 324 | A>V | No | EVA | |
| rs3388490183 | 325 | D>Y | No | EVA | |
| rs3390360381 | 328 | E>D | No | EVA | |
| rs3390428862 | 328 | E>V | No | EVA | |
| rs3388492497 | 387 | G>* | No | EVA | |
| rs3388493476 | 413 | D>G | No | EVA |
No associated diseases with P46467
7 regional properties for P46467
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | AAA+ ATPase domain | 166 - 302 | IPR003593 |
| domain | ATPase, AAA-type, core | 170 - 300 | IPR003959 |
| conserved_site | ATPase, AAA-type, conserved site | 272 - 291 | IPR003960 |
| domain | MIT domain | 4 - 82 | IPR007330 |
| domain | Spastin/Vps4, C-terminal | 381 - 441 | IPR015415 |
| domain | AAA ATPase, AAA+ lid domain | 325 - 357 | IPR041569 |
| domain | Vacuolar protein sorting-associated protein 4, MIT domain | 7 - 69 | IPR045253 |
Functions
| Description | ||
|---|---|---|
| EC Number | 3.6.4.6 | Acting on ATP; involved in cellular and subcellular movement |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
13 GO annotations of cellular component
| Name | Definition |
|---|---|
| ATPase complex | A protein complex which is capable of ATPase activity. |
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| endosome membrane | The lipid bilayer surrounding an endosome. |
| Flemming body | A cell part that is the central region of the midbody characterized by a gap in alpha-tubulin staining. It is a dense structure of antiparallel microtubules from the central spindle in the middle of the intercellular bridge. |
| late endosome membrane | The lipid bilayer surrounding a late endosome. |
| midbody | A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis. |
| nuclear pore | A protein complex providing a discrete opening in the nuclear envelope of a eukaryotic cell, where the inner and outer nuclear membranes are joined. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| spindle pole | Either of the ends of a spindle, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| ATP hydrolysis activity | Catalysis of the reaction: ATP + H2O = ADP + H+ phosphate. ATP hydrolysis is used in some reactions as an energy source, for example to catalyze a reaction or drive transport against a concentration gradient. |
| identical protein binding | Binding to an identical protein or proteins. |
| protein C-terminus binding | Binding to a protein C-terminus, the end of a peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue. |
| protein homodimerization activity | Binding to an identical protein to form a homodimer. |
| protein-containing complex binding | Binding to a macromolecular complex. |
32 GO annotations of biological process
| Name | Definition |
|---|---|
| autophagosome maturation | Removal of PI3P and Atg8/LC3 after the closure of the phagophore and before the fusion with the endosome/lysosome (e.g. mammals and insects) or vacuole (yeast), and that very likely destabilizes other Atg proteins and thus enables their efficient dissociation and recycling. |
| autophagy | The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation. |
| cholesterol transport | The directed movement of cholesterol, cholest-5-en-3-beta-ol, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| endosomal transport | The directed movement of substances mediated by an endosome, a membrane-bounded organelle that carries materials enclosed in the lumen or located in the endosomal membrane. |
| endosome organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of endosomes. |
| endosome to lysosome transport via multivesicular body sorting pathway | The directed movement of substances from endosomes to lysosomes by a pathway in which molecules are sorted into multivesicular bodies, which then fuse with the lysosome. |
| ESCRT III complex disassembly | The disaggregation of an ESCRT III complex into its constituent components. |
| late endosomal microautophagy | The autophagy process by which cytosolic proteins targeted for degradation are tagged with a chaperone and are directly transferred into and degraded in a late endosomal compartment. |
| late endosome to lysosome transport via multivesicular body sorting pathway | The directed movement of substances from late endosomes to lysosomes by a pathway in which molecules are sorted into multivesicular bodies, which then fuse with the lysosome. |
| membrane fission | A process that is carried out at the cellular level which results in the separation of a single continuous membrane into two membranes. |
| midbody abscission | The process by which the midbody, the cytoplasmic bridge that connects the two prospective daughter cells, is severed at the end of mitotic cytokinesis, resulting in two separate daughter cells. |
| mitotic metaphase plate congression | The cell cycle process in which chromosomes are aligned at the metaphase plate, a plane halfway between the poles of the mitotic spindle, during mitosis. |
| multivesicular body assembly | The aggregation, arrangement and bonding together of a set of components to form a multivesicular body, a type of late endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm. |
| multivesicular body sorting pathway | A vesicle-mediated transport process in which transmembrane proteins are ubiquitylated to facilitate their entry into luminal vesicles of multivesicular bodies (MVBs); upon subsequent fusion of MVBs with lysosomes or vacuoles, the cargo proteins are degraded. |
| negative regulation of cell death | Any process that decreases the rate or frequency of cell death. Cell death is the specific activation or halting of processes within a cell so that its vital functions markedly cease, rather than simply deteriorating gradually over time, which culminates in cell death. |
| negative regulation of exosomal secretion | Any process that stops, prevents or reduces the frequency, rate or extent of exosomal secretion. |
| nuclear membrane reassembly | The reformation of the nuclear membranes following their breakdown in the context of a normal process. |
| nucleus organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the nucleus. |
| plasma membrane repair | The resealing of a cell plasma membrane after cellular wounding due to, for instance, mechanical stress. |
| positive regulation of centriole elongation | Any process that activates or increases the frequency, rate or extent of centriole elongation. |
| positive regulation of exosomal secretion | Any process that activates or increases the frequency, rate or extent of exosomal secretion. |
| positive regulation of G2/M transition of mitotic cell cycle | Any signalling pathway that activates or increases the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G2 phase to M phase of the mitotic cell cycle. |
| potassium ion transport | The directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| protein depolymerization | The process in which protein polymers, compounds composed of a large number of component monomers, are broken down. Depolymerization occurs by the successive removal of monomers from an existing poly- or oligomeric protein. |
| protein transport | The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| regulation of centrosome duplication | Any process that modulates the frequency, rate or extent of centrosome duplication. Centrosome duplication is the replication of a centrosome, a structure comprised of a pair of centrioles and peri-centriolar material from which a microtubule spindle apparatus is organized. |
| regulation of mitotic spindle assembly | Any process that modulates the frequency, rate or extent of mitotic spindle assembly. |
| response to lipid | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipid stimulus. |
| ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the multivesicular body (MVB) sorting pathway; ubiquitin-tagged proteins are sorted into MVBs, and delivered to a lysosome/vacuole for degradation. |
| ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway | The chemical reactions and pathways resulting in the breakdown of a protein or peptide, via the multivesicular body (MVB) sorting pathway; proteins are sorted into MVBs, and delivered to a lysosome/vacuole for degradation. This process is independent of ubiquitination. |
| viral budding from plasma membrane | A viral budding that starts with formation of a membrane curvature in the host plasma membrane. |
| viral budding via host ESCRT complex | Viral budding which uses a host ESCRT protein complex, or complexes, to mediate the budding process. |
9 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P52917 | VPS4 | Vacuolar protein sorting-associated protein 4 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q0VD48 | VPS4B | Vacuolar protein sorting-associated protein 4B | Bos taurus (Bovine) | SS |
| Q9UN37 | VPS4A | Vacuolar protein sorting-associated protein 4A | Homo sapiens (Human) | EV |
| O75351 | VPS4B | Vacuolar protein sorting-associated protein 4B | Homo sapiens (Human) | PR |
| Q8VEJ9 | Vps4a | Vacuolar protein sorting-associated protein 4A | Mus musculus (Mouse) | PR |
| Q8K0T4 | Katnal1 | Katanin p60 ATPase-containing subunit A-like 1 | Mus musculus (Mouse) | PR |
| Q793F9 | Vps4a | Vacuolar protein sorting-associated protein 4A | Rattus norvegicus (Rat) | PR |
| D0FH76 | VPS4 | Vacuolar protein sorting-associated protein 4 | Bombyx mori (Silk moth) | SS |
| Q9ZNT0 | SKD1 | Protein SUPPRESSOR OF K(+) TRANSPORT GROWTH DEFECT 1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MASTNTNLQK | AIDLASKAAQ | EDKAGNYEEA | LQLYQHAVQY | FLHVVKYEAQ | GDKAKQSIRA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KCTEYLDRAE | KLKEYLKKKE | KKPQKPVKEE | QSGPVDEKGN | DSDGEAESDD | PEKKKLQNQL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| QGAIVIERPN | VKWSDVAGLE | GAKEALKEAV | ILPIKFPHLF | TGKRTPWRGI | LLFGPPGTGK |
| 190 | 200 | 210 | 220 | 230 | 240 |
| SYLAKAVATE | ANNSTFFSIS | SSDLVSKWLG | ESEKLVKNLF | QLARENKPSI | IFIDEIDSLC |
| 250 | 260 | 270 | 280 | 290 | 300 |
| GSRSENESEA | ARRIKTEFLV | QMQGVGVDND | GILVLGATNI | PWVLDSAIRR | RFEKRIYIPL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| PEAHARAAMF | RLHLGSTQNS | LTEADFQELG | RKTDGYSGAD | ISIIVRDALM | QPVRKVQSAT |
| 370 | 380 | 390 | 400 | 410 | 420 |
| HFKKVRGPSR | ADPNCIVNDL | LTPCSPGDPG | AIEMTWMDVP | GDKLLEPVVS | MWDMLRSLSS |
| 430 | 440 | ||||
| TKPTVNEQDL | LKLKKFTEDF | GQEG |