P25694 · CDC48_YEAST
- ProteinCell division control protein 48
- GeneCDC48
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids835 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
ATP-dependent chaperone which probably uses the energy provided by ATP hydrolysis to generate mechanical force to unfold substrate proteins, disassemble protein complexes, and disaggregate protein aggregates (PubMed:21454554, PubMed:31445887).
By recruiting and promoting the degradation of ubiquitinated proteins, plays a role in the ubiquitin fusion degradation (UFD) pathway (PubMed:16428438).
Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway which mediates the cytoplasmic elimination of misfolded proteins exported from the ER (PubMed:11740563, PubMed:11813000, PubMed:11847109, PubMed:21148305).
Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11733065, PubMed:11847109).
Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109).
Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972, PubMed:27044889).
Involved in spindle disassembly probably by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562).
Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23178123, PubMed:24261871).
CDC48 may provide the mechanical force that dislodges the polyubiquitinated nascent peptides from the exit channel (PubMed:23178123, PubMed:24261871).
Required for ribophagy, a process which relocalizes ribosomal particles into the vacuole for degradation in response to starvation (PubMed:20508643).
Component of the DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions and support a role in protein quality control (PubMed:29355480).
Substrate initially binds through the attached polyubiquitin chain to UDF1/NPL4 and then moves through the pore of the ATPase rings and is thereby unfolded (PubMed:31249134, PubMed:31249135).
Acts on a broad range of even well-folded proteins via ubiquitin-binding and unfolding to initiate substrate processing (PubMed:31249135).
Involved in degradation of mislocalized tail-anchored transmembrane proteins extracted from the mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10 (PubMed:31445887).
By recruiting and promoting the degradation of ubiquitinated proteins, plays a role in the ubiquitin fusion degradation (UFD) pathway (PubMed:16428438).
Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway which mediates the cytoplasmic elimination of misfolded proteins exported from the ER (PubMed:11740563, PubMed:11813000, PubMed:11847109, PubMed:21148305).
Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11733065, PubMed:11847109).
Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109).
Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972, PubMed:27044889).
Involved in spindle disassembly probably by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562).
Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23178123, PubMed:24261871).
CDC48 may provide the mechanical force that dislodges the polyubiquitinated nascent peptides from the exit channel (PubMed:23178123, PubMed:24261871).
Required for ribophagy, a process which relocalizes ribosomal particles into the vacuole for degradation in response to starvation (PubMed:20508643).
Component of the DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions and support a role in protein quality control (PubMed:29355480).
Substrate initially binds through the attached polyubiquitin chain to UDF1/NPL4 and then moves through the pore of the ATPase rings and is thereby unfolded (PubMed:31249134, PubMed:31249135).
Acts on a broad range of even well-folded proteins via ubiquitin-binding and unfolding to initiate substrate processing (PubMed:31249135).
Involved in degradation of mislocalized tail-anchored transmembrane proteins extracted from the mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10 (PubMed:31445887).
Miscellaneous
Present with 78400 molecules/cell in log phase SD medium.
Catalytic activity
- ATP + H2O = ADP + phosphate + H+
Activity regulation
The first ATP-binding region has low ATPase activity (By similarity).
The second ATP-binding region is responsible for ATPase activity (By similarity).
ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (PubMed:21454554).
While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (By similarity).
ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (By similarity).
The second ATP-binding region is responsible for ATPase activity (By similarity).
ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (PubMed:21454554).
While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (By similarity).
ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 257-263 | ATP 1 (UniProtKB | ChEBI) | |||
Binding site | 358 | ATP 1 (UniProtKB | ChEBI) | |||
Binding site | 394 | ATP 1 (UniProtKB | ChEBI) | |||
Binding site | 531-536 | ATP 2 (UniProtKB | ChEBI) | |||
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCell division control protein 48
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP25694
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Bound loosely to components of the microsomal fraction.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Mutagenesis | 261 | Moderate reduction in growth rate. | |||
Mutagenesis | 261 | Probable loss of ATP binding. Complete loss of catalytic activity. | |||
Mutagenesis | 315 | Moderate reduction in growth rate. | |||
Mutagenesis | 315 | Severe loss of catalytic activity without affecting cooperativity between the 2 ATP-binding regions. Slight reduction in growth rate. | |||
Mutagenesis | 315 | Severe reduction in growth rate. | |||
Mutagenesis | 315 | Severe loss of catalytic activity and cooperativity between the 2 ATP-binding regions. Lethal. Restores cell growth; when associated with A-358; A-369; S-471; A-471 or H-475. | |||
Mutagenesis | 358 | Slight reduction in growth rate. Restores cell growth; when associated with Q-315. | |||
Mutagenesis | 369 | No effect on growth rate. Restores cell growth; when associated with Q-315. | |||
Mutagenesis | 471 | Restores cell growth; when associated with Q-315. | |||
Mutagenesis | 475 | Restores cell growth; when associated with Q-315. | |||
Mutagenesis | 534 | Severe loss of catalytic activity. Lethal. | |||
Mutagenesis | 588 | Moderate reduction in growth rate. | |||
Mutagenesis | 588 | Lethal. | |||
Mutagenesis | 645 | Lethal. | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000084587 | 1-835 | Cell division control protein 48 | ||
Cross-link | 305 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 322 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 346 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Modified residue | 472 | Phosphoserine | |||
Modified residue | 519 | Phosphoserine | |||
Cross-link | 522 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 539 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 594 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 673 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Modified residue | 735 | Phosphothreonine | |||
Modified residue | 770 | Phosphoserine | |||
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the heterotrimeric CDC48-NPL4-UFD1 ATPase complex (PubMed:16873066).
The CDC48-NPL4-UFD1 ATPase complex interacts with the HRD1 ubiquitin ligase complex composed of the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and CDC48-binding protein UBX2 (PubMed:16873066).
Interaction between the complexes is mediated by interaction between CDC48-NPL4-UFD1 complex member CDC48 and HRD1 complex member UBX2 (PubMed:16873066).
Forms a complex composed of CDC48, NPL4, UFD1, UFD2 and SHP1 (PubMed:16427015).
Forms a complex composed of CDC48, NPL4, UFD1, DOA1, SHP1 and deubiquitinase OTU1; within the complex interacts with DOA1/UFD3 and OTU1 to prevent multiubiquitination of substrates (PubMed:16427015).
Interacts with UFD2, to add further ubiquitin moieties; the interaction with UFD2 is prevented by DOA1/UFD3 (PubMed:16427015).
Forms a complex composed of CDC48, DOA1, deubiquitinase UBP3 and probably BRE5; within the complex interacts with DOA1 and UBP3 (PubMed:20508643).
Interacts (via C-terminus) with DOA1 (via PUL domain); the interaction is direct (PubMed:16428438, PubMed:19805280, PubMed:27044889).
Interacts with NPL4 (PubMed:11598205, PubMed:11733065, PubMed:31249134).
Interacts with SHP1/UBX1, UBX2, UBX3, UBX4, UBX5, UBX6 and UBX7 (PubMed:15258615, PubMed:31249134).
Interacts with VMS1; the interaction recruits CDC48 to the mitochondria in response to mitochondrial stress (PubMed:21070972, PubMed:21148305).
Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase RKR1/LTN1, RQC1 and RQC2, as well as CDC48 and its ubiquitin-binding cofactors (PubMed:23178123, PubMed:23479637).
RQC forms a stable complex with 60S ribosomal subunits (PubMed:23178123, PubMed:23479637).
Interacts with ASE1 and CDC5; the interaction is likely to result in their degradation (PubMed:14636562).
Component of the DSCc E3 ligase complexes composed of at least TUL1, DSC2, DSC3, UBX3, CDC48 as well as VLD1 for the vacuole-localized complex or GLD1 for the Golgi/endosome-localized complex (PubMed:29355480).
The CDC48-NPL4-UFD1 ATPase complex interacts with the HRD1 ubiquitin ligase complex composed of the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and CDC48-binding protein UBX2 (PubMed:16873066).
Interaction between the complexes is mediated by interaction between CDC48-NPL4-UFD1 complex member CDC48 and HRD1 complex member UBX2 (PubMed:16873066).
Forms a complex composed of CDC48, NPL4, UFD1, UFD2 and SHP1 (PubMed:16427015).
Forms a complex composed of CDC48, NPL4, UFD1, DOA1, SHP1 and deubiquitinase OTU1; within the complex interacts with DOA1/UFD3 and OTU1 to prevent multiubiquitination of substrates (PubMed:16427015).
Interacts with UFD2, to add further ubiquitin moieties; the interaction with UFD2 is prevented by DOA1/UFD3 (PubMed:16427015).
Forms a complex composed of CDC48, DOA1, deubiquitinase UBP3 and probably BRE5; within the complex interacts with DOA1 and UBP3 (PubMed:20508643).
Interacts (via C-terminus) with DOA1 (via PUL domain); the interaction is direct (PubMed:16428438, PubMed:19805280, PubMed:27044889).
Interacts with NPL4 (PubMed:11598205, PubMed:11733065, PubMed:31249134).
Interacts with SHP1/UBX1, UBX2, UBX3, UBX4, UBX5, UBX6 and UBX7 (PubMed:15258615, PubMed:31249134).
Interacts with VMS1; the interaction recruits CDC48 to the mitochondria in response to mitochondrial stress (PubMed:21070972, PubMed:21148305).
Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase RKR1/LTN1, RQC1 and RQC2, as well as CDC48 and its ubiquitin-binding cofactors (PubMed:23178123, PubMed:23479637).
RQC forms a stable complex with 60S ribosomal subunits (PubMed:23178123, PubMed:23479637).
Interacts with ASE1 and CDC5; the interaction is likely to result in their degradation (PubMed:14636562).
Component of the DSCc E3 ligase complexes composed of at least TUL1, DSC2, DSC3, UBX3, CDC48 as well as VLD1 for the vacuole-localized complex or GLD1 for the Golgi/endosome-localized complex (PubMed:29355480).
Binary interactions
Complex viewer
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-21 | Disordered | |||
Region | 720-746 | Disordered | |||
Compositional bias | 792-820 | Polar residues | |||
Region | 792-835 | Disordered | |||
Sequence similarities
Belongs to the AAA ATPase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length835
- Mass (Da)91,996
- Last updated1996-10-01 v3
- MD5 Checksum63D5942C18CA5EAE438A39ADB41B9464
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 792-820 | Polar residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X56956 EMBL· GenBank· DDBJ | CAA40276.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z74174 EMBL· GenBank· DDBJ | CAA98694.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006938 EMBL· GenBank· DDBJ | DAA11734.1 EMBL· GenBank· DDBJ | Genomic DNA |