Essential maintenance is planned to begin on Fri Jan 24 2025. The website may be temporarily unavailable. Please use our fallback: https://wwwdev.ebi.ac.uk/uniprot/front-end/fallback/ in case of any outage.

P25694 · CDC48_YEAST

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).

Miscellaneous

Present with 78400 molecules/cell in log phase SD medium.

Catalytic activity

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).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site257-263ATP 1 (UniProtKB | ChEBI)
Binding site358ATP 1 (UniProtKB | ChEBI)
Binding site394ATP 1 (UniProtKB | ChEBI)
Binding site531-536ATP 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular ComponentCdc48p-Npl4p-Vms1p AAA ATPase complex
Cellular Componentcytosol
Cellular ComponentDoa10p ubiquitin ligase complex
Cellular Componentendoplasmic reticulum membrane
Cellular ComponentHrd1p ubiquitin ligase ERAD-L complex
Cellular Componentmating projection tip
Cellular Componentmitochondrion
Cellular Componentnucleus
Cellular Componentreplisome
Cellular ComponentRQC complex
Cellular ComponentVCP-NPL4-UFD1 AAA ATPase complex
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functionidentical protein binding
Molecular Functionpolyubiquitin modification-dependent protein binding
Molecular Functionprotein phosphatase regulator activity
Molecular Functionubiquitin binding
Biological ProcessATP metabolic process
Biological Processautophagosome maturation
Biological Processcytoplasm protein quality control by the ubiquitin-proteasome system
Biological ProcessDNA replication termination
Biological Processendoplasmic reticulum membrane fusion
Biological Processendosome to plasma membrane protein transport
Biological ProcessERAD pathway
Biological Processmacroautophagy
Biological Processmitochondria-associated ubiquitin-dependent protein catabolic process
Biological Processmitotic DNA replication termination
Biological Processmitotic spindle disassembly
Biological Processnonfunctional rRNA decay
Biological Processnuclear protein quality control by the ubiquitin-proteasome system
Biological Processpiecemeal microautophagy of the nucleus
Biological Processpositive regulation of mitochondrial fusion
Biological Processpositive regulation of protein localization to nucleus
Biological Processproteasome-mediated ubiquitin-dependent protein catabolic process
Biological Processprotein quality control for misfolded or incompletely synthesized proteins
Biological Processprotein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Biological Processprotein-containing complex disassembly
Biological Processrescue of stalled ribosome
Biological Processretrograde protein transport, ER to cytosol
Biological Processribophagy
Biological Processribosome-associated ubiquitin-dependent protein catabolic process
Biological ProcessSCF complex disassembly in response to cadmium stress
Biological Processsister chromatid biorientation
Biological Processstress-induced homeostatically regulated protein degradation pathway

Keywords

Enzyme and pathway databases

Protein family/group databases

    • 3.A.16.1.2the endoplasmic reticular retrotranslocon (er-rt) family

Names & Taxonomy

Protein names

  • Recommended name
    Cell division control protein 48
  • EC number
  • Alternative names
    • Cell division cycle protein 48
    • Transitional endoplasmic reticulum ATPase homolog

Gene names

    • Name
      CDC48
    • Ordered locus names
      YDL126C

Organism names

Accessions

  • Primary accession
    P25694
  • Secondary accessions
    • D6VRM4

Proteomes

Organism-specific databases

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis261Moderate reduction in growth rate.
Mutagenesis261Probable loss of ATP binding. Complete loss of catalytic activity.
Mutagenesis315Moderate reduction in growth rate.
Mutagenesis315Severe loss of catalytic activity without affecting cooperativity between the 2 ATP-binding regions. Slight reduction in growth rate.
Mutagenesis315Severe reduction in growth rate.
Mutagenesis315Severe 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.
Mutagenesis358Slight reduction in growth rate. Restores cell growth; when associated with Q-315.
Mutagenesis369No effect on growth rate. Restores cell growth; when associated with Q-315.
Mutagenesis471Restores cell growth; when associated with Q-315.
Mutagenesis475Restores cell growth; when associated with Q-315.
Mutagenesis534Severe loss of catalytic activity. Lethal.
Mutagenesis588Moderate reduction in growth rate.
Mutagenesis588Lethal.
Mutagenesis645Lethal.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, cross-link, modified residue.

Type
IDPosition(s)Description
ChainPRO_00000845871-835Cell division control protein 48
Cross-link305Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link346Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue472Phosphoserine
Modified residue519Phosphoserine
Cross-link522Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link539Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link594Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link673Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue735Phosphothreonine
Modified residue770Phosphoserine

Keywords

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).

Binary interactions

Complex viewer

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias.

Type
IDPosition(s)Description
Region1-21Disordered
Region720-746Disordered
Compositional bias792-820Polar residues
Region792-835Disordered

Sequence similarities

Belongs to the AAA ATPase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    835
  • Mass (Da)
    91,996
  • Last updated
    1996-10-01 v3
  • MD5 Checksum
    63D5942C18CA5EAE438A39ADB41B9464
MGEEHKPLLDASGVDPREEDKTATAILRRKKKDNMLLVDDAINDDNSVIAINSNTMDKLELFRGDTVLVKGKKRKDTVLIVLIDDELEDGACRINRVVRNNLRIRLGDLVTIHPCPDIKYATRISVLPIADTIEGITGNLFDVFLKPYFVEAYRPVRKGDHFVVRGGMRQVEFKVVDVEPEEYAVVAQDTIIHWEGEPINREDEENNMNEVGYDDIGGCRKQMAQIREMVELPLRHPQLFKAIGIKPPRGVLMYGPPGTGKTLMARAVANETGAFFFLINGPEVMSKMAGESESNLRKAFEEAEKNAPAIIFIDEIDSIAPKRDKTNGEVERRVVSQLLTLMDGMKARSNVVVIAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEVLRIHTKNMKLADDVDLEALAAETHGYVGADIASLCSEAAMQQIREKMDLIDLDEDEIDAEVLDSLGVTMDNFRFALGNSNPSALRETVVESVNVTWDDVGGLDEIKEELKETVEYPVLHPDQYTKFGLSPSKGVLFYGPPGTGKTLLAKAVATEVSANFISVKGPELLSMWYGESESNIRDIFDKARAAAPTVVFLDELDSIAKARGGSLGDAGGASDRVVNQLLTEMDGMNAKKNVFVIGATNRPDQIDPAILRPGRLDQLIYVPLPDENARLSILNAQLRKTPLEPGLELTAIAKATQGFSGADLLYIVQRAAKYAIKDSIEAHRQHEAEKEVKVEGEDVEMTDEGAKAEQEPEVDPVPYITKEHFAEAMKTAKRSVSDAELRRYEAYSQQMKASRGQFSNFNFNDAPLGTTATDNANSNNSAPSGAGAAFGSNAEEDDDLYS

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias792-820Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
Help