Protein: Cell division control protein 48 (EC 3.6.4.6) (Cell division cycle protein 48) (Transitional endoplasmic reticulum ATPase homolog) (P25694)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
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. By recruiting and promoting the degradation of ubiquitinated proteins, plays a role in the ubiquitin fusion degradation (UFD) pathway. Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway which mediates the cytoplasmic elimination of misfolded proteins exported from the ER. Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1. Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD. Regulates ubiquitin-mediated mitochondria protein degradation. Involved in spindle disassembly probably by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis. 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. CDC48 may provide the mechanical force that dislodges the polyubiquitinated nascent peptides from the exit channel. Required for ribophagy, a process which relocalizes ribosomal particles into the vacuole for degradation in response to starvation. 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. 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. Acts on a broad range of even well-folded proteins via ubiquitin-binding and unfolding to initiate substrate processing. Involved in degradation of mislocalized tail-anchored transmembrane proteins extracted from the mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10.
Subcellular location: Microsome {ECO:0000269|PubMed:11733065}. Endoplasmic reticulum {ECO:0000269|PubMed:21148305}. Cytoplasm {ECO:0000269|PubMed:21148305}. Note=Bound loosely to components of the microsomal fraction. {ECO:0000269|PubMed:11733065}.
Interaction partners:
- Ribosome quality control complex subunit 1
- Protein DOA1
- ERAD-associated E3 ubiquitin-protein ligase HRD1
- E4 ubiquitin-protein ligase UFD2
- Ubiquitin thioesterase OTU1
- Ubiquitin fusion degradation protein 1
- tRNA endonuclease VMS1
- DER1-like family member protein 1
- Degradation in the endoplasmic reticulum protein 1
- ERAD-associated E3 ubiquitin-protein ligase DOA10
Sequence:
MGEEHKPLLDASGVDPREEDKTATAILRRKKKDNMLLVDDAINDDNSVIAINSNTMDKLELFRGDTVLVKGKKRKDTVLIVLIDDELEDGACRINRVVRNNLRIRLGDLVTIHPCPDIKYATRISVLPIADTIEGITGNLFDVFLKPYFVEAYRPVRKGDHFVVRGGMRQVEFKVVDVEPEEYAVVAQDTIIHWEGEPINREDEENNMNEVGYDDIGGCRKQMAQIREMVELPLRHPQLFKAIGIKPPRGVLMYGPPGTGKTLMARAVANETGAFFFLINGPEVMSKMAGESESNLRKAFEEAEKNAPAIIFIDEIDSIAPKRDKTNGEVERRVVSQLLTLMDGMKARSNVVVIAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEVLRIHTKNMKLADDVDLEALAAETHGYVGADIASLCSEAAMQQIREKMDLIDLDEDEIDAEVLDSLGVTMDNFRFALGNSNPSALRETVVESVNVTWDDVGGLDEIKEELKETVEYPVLHPDQYTKFGLSPSKGVLFYGPPGTGKTLLAKAVATEVSANFISVKGPELLSMWYGESESNIRDIFDKARAAAPTVVFLDELDSIAKARGGSLGDAGGASDRVVNQLLTEMDGMNAKKNVFVIGATNRPDQIDPAILRPGRLDQLIYVPLPDENARLSILNAQLRKTPLEPGLELTAIAKATQGFSGADLLYIVQRAAKYAIKDSIEAHRQHEAEKEVKVEGEDVEMTDEGAKAEQEPEVDPVPYITKEHFAEAMKTAKRSVSDAELRRYEAYSQQMKASRGQFSNFNFNDAPLGTTATDNANSNNSAPSGAGAAFGSNAEEDDDLYS