| IED ID | IndEnz0002005472 |
| Enzyme Type ID | protease005472 |
| Protein Name |
Cell division control protein 48 EC 3.6.4.6 Cell division cycle protein 48 Transitional endoplasmic reticulum ATPase homolog |
| Gene Name | CDC48 YDL126C |
| Organism | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Saccharomycotina (true yeasts) Saccharomycetes Saccharomycetales Saccharomycetaceae Saccharomyces Saccharomyces cerevisiae (Baker's yeast) Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Enzyme Sequence | MGEEHKPLLDASGVDPREEDKTATAILRRKKKDNMLLVDDAINDDNSVIAINSNTMDKLELFRGDTVLVKGKKRKDTVLIVLIDDELEDGACRINRVVRNNLRIRLGDLVTIHPCPDIKYATRISVLPIADTIEGITGNLFDVFLKPYFVEAYRPVRKGDHFVVRGGMRQVEFKVVDVEPEEYAVVAQDTIIHWEGEPINREDEENNMNEVGYDDIGGCRKQMAQIREMVELPLRHPQLFKAIGIKPPRGVLMYGPPGTGKTLMARAVANETGAFFFLINGPEVMSKMAGESESNLRKAFEEAEKNAPAIIFIDEIDSIAPKRDKTNGEVERRVVSQLLTLMDGMKARSNVVVIAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEVLRIHTKNMKLADDVDLEALAAETHGYVGADIASLCSEAAMQQIREKMDLIDLDEDEIDAEVLDSLGVTMDNFRFALGNSNPSALRETVVESVNVTWDDVGGLDEIKEELKETVEYPVLHPDQYTKFGLSPSKGVLFYGPPGTGKTLLAKAVATEVSANFISVKGPELLSMWYGESESNIRDIFDKARAAAPTVVFLDELDSIAKARGGSLGDAGGASDRVVNQLLTEMDGMNAKKNVFVIGATNRPDQIDPAILRPGRLDQLIYVPLPDENARLSILNAQLRKTPLEPGLELTAIAKATQGFSGADLLYIVQRAAKYAIKDSIEAHRQHEAEKEVKVEGEDVEMTDEGAKAEQEPEVDPVPYITKEHFAEAMKTAKRSVSDAELRRYEAYSQQMKASRGQFSNFNFNDAPLGTTATDNANSNNSAPSGAGAAFGSNAEEDDDLYS |
| Enzyme Length | 835 |
| Uniprot Accession Number | P25694 |
| Absorption | |
| Active Site | |
| Activity Regulation | 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). {ECO:0000250|UniProtKB:P54811, ECO:0000269|PubMed:21454554}. |
| Binding Site | BINDING 358; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072; BINDING 394; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6; Evidence={ECO:0000269|PubMed:21454554}; |
| DNA Binding | |
| EC Number | 3.6.4.6 |
| Enzyme 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:11813000, PubMed:11740563, 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:11847109, PubMed:11733065). 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:31249135, PubMed:31249134). 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). {ECO:0000269|PubMed:11733065, ECO:0000269|PubMed:11740563, ECO:0000269|PubMed:11813000, ECO:0000269|PubMed:11847109, ECO:0000269|PubMed:14636562, ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:20508643, ECO:0000269|PubMed:21070972, ECO:0000269|PubMed:21148305, ECO:0000269|PubMed:21454554, ECO:0000269|PubMed:23178123, ECO:0000269|PubMed:24261871, ECO:0000269|PubMed:27044889, ECO:0000269|PubMed:29355480, ECO:0000269|PubMed:31249134, ECO:0000269|PubMed:31249135, ECO:0000269|PubMed:31445887}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 257..263; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072; NP_BIND 531..536; /note=ATP 2; /evidence=ECO:0000250|UniProtKB:Q01853 |
| Features | Binding site (2); Chain (1); Compositional bias (1); Cross-link (7); Modified residue (4); Mutagenesis (14); Nucleotide binding (2); Region (3) |
| Keywords | 3D-structure;ATP-binding;Cell cycle;Chaperone;Cytoplasm;Endoplasmic reticulum;Hydrolase;Isopeptide bond;Microsome;Nucleotide-binding;Phosphoprotein;Protein transport;Reference proteome;Repeat;Transport;Ubl conjugation |
| Interact With | P53741; Itself; P38307; P36037; Q08109; Q05787; P33755; P32628; P06778; P34223; Q12306; P40318; Q01477; Q04228; Q12229; P54730; Q06682; P47049; P38349; P53044; P54860; Q04311 |
| Induction | |
| Subcellular Location | 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}. |
| Modified Residue | MOD_RES 472; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18407956"; MOD_RES 519; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"; MOD_RES 735; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"; MOD_RES 770; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17287358, ECO:0007744|PubMed:17330950" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | Electron microscopy (5) |
| Cross Reference PDB | 6OA9; 6OAA; 6OAB; 6OMB; 6OPC; |
| Mapped Pubmed ID | 10350210; 10688190; 11097021; 11283351; 11576446; 11679167; 11738144; 11739805; 11756557; 11805826; 12015140; 12172961; 12383799; 12743025; 12847084; 12847107; 12860974; 12881414; 14514884; 14557244; 14607830; 14738753; 14755638; 14759368; 15004522; 15167887; 15200949; 15215312; 15527405; 15556039; 15571806; 15598467; 15652483; 15699485; 15738968; 15910746; 16056265; 16056268; 16179952; 16179953; 16212502; 16234241; 16250894; 16316751; 16332527; 16397583; 16429126; 16455487; 16554755; 16619026; 16816426; 16822868; 16873065; 16919153; 16921443; 16971477; 17006544; 17083136; 17087770; 17101700; 17142044; 17202270; 17207637; 17289586; 17395182; 17453165; 17505521; 17945519; 18174173; 18191224; 18208399; 18284922; 18298957; 18315532; 18355456; 18406356; 18407841; 18583943; 18719252; 18725537; 18782613; 18812321; 18854435; 19013276; 19015277; 19061897; 19286982; 19324879; 19359248; 19401679; 19416362; 19497384; 19536198; 19696741; 19841731; 19887378; 19915556; 19923195; 19926288; 20038635; 20075938; 20110349; 20118070; 20130684; 20178855; 20206597; 20219571; 20383156; 20483956; 20519439; 20579315; 20846524; 20855502; 21029298; 21074049; 21076182; 21081964; 21150310; 21160277; 21179020; 21190544; 21211725; 21222279; 21266254; 21282470; 21427232; 21486945; 21490136; 21526151; 21548784; 21734642; 21741246; 21801748; 21807993; 21896481; 21936843; 21949850; 22094424; 22188402; 22209905; 22214660; 22345606; 22350912; 22454508; 22505030; 22580068; 22718752; 22728077; 22817540; 22829918; 23000173; 23209158; 23217712; 23226681; 23358411; 23416749; 23418575; 23479442; 23536702; 23583075; 23624404; 23653356; 23791177; 23793018; 23874617; 23943356; 23988329; 24121501; 24155900; 24225956; 24297164; 24351022; 24569878; 24817020; 24833120; 24855027; 24893221; 25032908; 25073740; 25079602; 25083872; 25183520; 25190516; 25215493; 25231236; 25333764; 25342810; 25556859; 25564609; 25616896; 25625920; 25677381; 25753421; 25814926; 25835602; 25999509; 26255844; 26272996; 26349035; 26362128; 26362318; 26365526; 26656161; 26849222; 26945625; 27048816; 27129255; 27226596; 27384026; 27385344; 27566164; 27715443; 27769718; 27787227; 27977397; 28077573; 28475898; 28525741; 29309037; 29444958; 31368600; 31740565; 31804690; 32817489; 33172985; 33388824; 34389719; 7492595; 7553849; 8521820; 8890162; 8970740; 9436996; 9506516; 9695811; |
| Motif | |
| Gene Encoded By | |
| Mass | 91,996 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:13065 |
| Cross Reference Brenda |