TERA1_CAEEL
ID TERA1_CAEEL Reviewed; 809 AA.
AC P54811;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Transitional endoplasmic reticulum ATPase homolog 1 {ECO:0000305};
DE EC=3.6.4.6 {ECO:0000269|PubMed:18782221, ECO:0000269|PubMed:18854144, ECO:0000269|PubMed:21454554};
DE AltName: Full=Cell division cycle-related protein 48.1 {ECO:0000312|WormBase:C06A1.1};
DE AltName: Full=p97/CDC48 homolog 1 {ECO:0000305};
GN Name=cdc-48.1 {ECO:0000312|WormBase:C06A1.1};
GN ORFNames=C06A1.1 {ECO:0000312|WormBase:C06A1.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=15716356; DOI=10.1091/mbc.e04-08-0726;
RA Poteryaev D., Squirrell J.M., Campbell J.M., White J.G., Spang A.;
RT "Involvement of the actin cytoskeleton and homotypic membrane fusion in ER
RT dynamics in Caenorhabditis elegans.";
RL Mol. Biol. Cell 16:2139-2153(2005).
RN [3]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=16701565; DOI=10.1016/j.bbrc.2006.04.160;
RA Yamauchi S., Yamanaka K., Ogura T.;
RT "Comparative analysis of expression of two p97 homologues in Caenorhabditis
RT elegans.";
RL Biochem. Biophys. Res. Commun. 345:746-753(2006).
RN [4]
RP FUNCTION, INTERACTION WITH CDC-48.2; UFD-1 AND UBXN-1, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16647269; DOI=10.1016/j.jsb.2006.02.015;
RA Mouysset J., Kaehler C., Hoppe T.;
RT "A conserved role of Caenorhabditis elegans CDC-48 in ER-associated protein
RT degradation.";
RL J. Struct. Biol. 156:41-49(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17512499; DOI=10.1016/j.bbrc.2007.05.022;
RA Sasagawa Y., Yamanaka K., Nishikori S., Ogura T.;
RT "Caenorhabditis elegans p97/CDC-48 is crucial for progression of meiosis
RT I.";
RL Biochem. Biophys. Res. Commun. 358:920-924(2007).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17825049; DOI=10.1111/j.1365-2443.2007.01108.x;
RA Sasagawa Y., Yamanaka K., Ogura T.;
RT "ER E3 ubiquitin ligase HRD-1 and its specific partner chaperone BiP play
RT important roles in ERAD and developmental growth in Caenorhabditis
RT elegans.";
RL Genes Cells 12:1063-1073(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18097415; DOI=10.1038/nature06388;
RA Ramadan K., Bruderer R., Spiga F.M., Popp O., Baur T., Gotta M.,
RA Meyer H.H.;
RT "Cdc48/p97 promotes reformation of the nucleus by extracting the kinase
RT Aurora B from chromatin.";
RL Nature 450:1258-1262(2007).
RN [8]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH UNC-45; UFD-2 AND CHN-1,
RP INTERACTION WITH CDC-48.2 AND UFD-2, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 804-ASP--ASN-809.
RX PubMed=17369820; DOI=10.1038/ncb1554;
RA Janiesch P.C., Kim J., Mouysset J., Barikbin R., Lochmueller H.,
RA Cassata G., Krause S., Hoppe T.;
RT "The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to
RT human myopathy.";
RL Nat. Cell Biol. 9:379-390(2007).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, LACK OF INTERACTION WITH AIR-2, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=18854144; DOI=10.1016/j.devcel.2008.08.005;
RA Heallen T.R., Adams H.P., Furuta T., Verbrugghe K.J., Schumacher J.M.;
RT "An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and
RT activity of the C. elegans Aurora B kinase AIR-2.";
RL Dev. Cell 15:603-616(2008).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS
RP OF LYS-257 AND LYS-530.
RX PubMed=18782221; DOI=10.1111/j.1365-2443.2008.01214.x;
RA Nishikori S., Yamanaka K., Sakurai T., Esaki M., Ogura T.;
RT "p97 Homologs from Caenorhabditis elegans, CDC-48.1 and CDC-48.2, suppress
RT the aggregate formation of huntingtin exon1 containing expanded polyQ
RT repeat.";
RL Genes Cells 13:827-838(2008).
RN [11]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH HIM-6 AND CRP-1, INTERACTION
RP WITH HIM-6 AND CRP-1, AND DISRUPTION PHENOTYPE.
RX PubMed=18458060; DOI=10.1128/mcb.02252-07;
RA Caruso M.E., Jenna S., Bouchecareilh M., Baillie D.L., Boismenu D.,
RA Halawani D., Latterich M., Chevet E.;
RT "GTPase-mediated regulation of the unfolded protein response in
RT Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48.";
RL Mol. Cell. Biol. 28:4261-4274(2008).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18728180; DOI=10.1073/pnas.0805944105;
RA Mouysset J., Deichsel A., Moser S., Hoege C., Hyman A.A., Gartner A.,
RA Hoppe T.;
RT "Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for
RT efficient DNA replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12879-12884(2008).
RN [13]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ATX-3 AND UBXN-5, AND
RP INTERACTION WITH ATX-3 AND UBXN-5.
RX PubMed=19545544; DOI=10.1016/j.bbrc.2009.06.092;
RA Rodrigues A.J., Neves-Carvalho A., Ferro A., Rokka A., Corthals G.,
RA Logarinho E., Maciel P.;
RT "ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis
RT elegans.";
RL Biochem. Biophys. Res. Commun. 386:575-581(2009).
RN [14]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=19773360; DOI=10.1242/jcs.052415;
RA Sasagawa Y., Otani M., Higashitani N., Higashitani A., Sato K., Ogura T.,
RA Yamanaka K.;
RT "Caenorhabditis elegans p97 controls germline-specific sex determination by
RT controlling the TRA-1 level in a CUL-2-dependent manner.";
RL J. Cell Sci. 122:3663-3672(2009).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH UBXN-3; UFD-1 AND NPL-4.1, INTERACTION
RP WITH UBXN-1; UBXN-2; UBXN-3; UBXN-4; UBXN-6 AND UFD-1, SUBCELLULAR
RP LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20977550; DOI=10.1111/j.1365-2443.2010.01454.x;
RA Sasagawa Y., Yamanaka K., Saito-Sasagawa Y., Ogura T.;
RT "Caenorhabditis elegans UBX cofactors for CDC-48/p97 control
RT spermatogenesis.";
RL Genes Cells 15:1201-1215(2010).
RN [16]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF LYS-257; GLU-311; ASN-354; ARG-365; PRO-467; ARG-471;
RP LYS-530; GLU-584; ASN-631 AND ARG-642.
RX PubMed=21454554; DOI=10.1074/jbc.m110.201400;
RA Nishikori S., Esaki M., Yamanaka K., Sugimoto S., Ogura T.;
RT "Positive cooperativity of the p97 AAA ATPase is critical for essential
RT functions.";
RL J. Biol. Chem. 286:15815-15820(2011).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21981920; DOI=10.1016/j.molcel.2011.08.028;
RA Franz A., Orth M., Pirson P.A., Sonneville R., Blow J.J., Gartner A.,
RA Stemmann O., Hoppe T.;
RT "CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation
RT to ensure faithful DNA replication.";
RL Mol. Cell 44:85-96(2011).
RN [18]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ATX-3 AND UFD-2, INTERACTION
RP WITH ATX-3 AND UFD-2, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 804-ASP--ASN-809.
RX PubMed=21317884; DOI=10.1038/ncb2200;
RA Kuhlbrodt K., Janiesch P.C., Kevei E., Segref A., Barikbin R., Hoppe T.;
RT "The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and
RT proteostasis.";
RL Nat. Cell Biol. 13:273-281(2011).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22768338; DOI=10.1371/journal.pone.0040145;
RA Miedel M.T., Graf N.J., Stephen K.E., Long O.S., Pak S.C., Perlmutter D.H.,
RA Silverman G.A., Luke C.J.;
RT "A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-
RT associated degradation in C. elegans.";
RL PLoS ONE 7:E40145-E40145(2012).
RN [20]
RP INTERACTION WITH UBXN-2.
RX PubMed=23649807; DOI=10.1083/jcb.201209107;
RA Kress E., Schwager F., Holtackers R., Seiler J., Prodon F., Zanin E.,
RA Eiteneuer A., Toya M., Sugimoto A., Meyer H., Meraldi P., Gotta M.;
RT "The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the
RT centrosomal recruitment of Aurora A.";
RL J. Cell Biol. 201:559-575(2013).
RN [21]
RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF LYS-530 AND GLU-584.
RX PubMed=24055316; DOI=10.1016/j.str.2013.08.017;
RA Noi K., Yamamoto D., Nishikori S., Arita-Morioka K., Kato T., Ando T.,
RA Ogura T.;
RT "High-speed atomic force microscopic observation of ATP-dependent rotation
RT of the AAA+ chaperone p97.";
RL Structure 21:1992-2002(2013).
RN [22]
RP INTERACTION WITH UFD-3 AND CDC-48.2, AND SUBCELLULAR LOCATION.
RX PubMed=25721663; DOI=10.1016/j.bbrc.2015.02.088;
RA Murayama Y., Ogura T., Yamanaka K.;
RT "Characterization of C-terminal adaptors, UFD-2 and UFD-3, of CDC-48 on the
RT polyglutamine aggregation in C. elegans.";
RL Biochem. Biophys. Res. Commun. 459:154-160(2015).
RN [23]
RP FUNCTION.
RX PubMed=25652260; DOI=10.15252/embr.201439123;
RA Marza E., Taouji S., Barroso K., Raymond A.A., Guignard L., Bonneu M.,
RA Pallares-Lupon N., Dupuy J.W., Fernandez-Zapico M.E., Rosenbaum J.,
RA Palladino F., Dupuy D., Chevet E.;
RT "Genome-wide screen identifies a novel p97/CDC-48-dependent pathway
RT regulating ER-stress-induced gene transcription.";
RL EMBO Rep. 16:332-340(2015).
RN [24]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH UBXN-3 AND CDT-1, INTERACTION
RP WITH UBXN-3 AND CDT-1, AND DISRUPTION PHENOTYPE.
RX PubMed=26842564; DOI=10.1038/ncomms10612;
RA Franz A., Pirson P.A., Pilger D., Halder S., Achuthankutty D., Kashkar H.,
RA Ramadan K., Hoppe T.;
RT "Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard
RT DNA replication fork progression.";
RL Nat. Commun. 7:10612-10612(2016).
RN [25]
RP INTERACTION WITH UFD-2.
RX PubMed=27669035; DOI=10.1038/nsmb.3296;
RA Ackermann L., Schell M., Pokrzywa W., Kevei E., Gartner A., Schumacher B.,
RA Hoppe T.;
RT "E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break
RT repair and apoptosis.";
RL Nat. Struct. Mol. Biol. 23:995-1002(2016).
RN [26]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28368371; DOI=10.1038/ncb3500;
RA Sonneville R., Moreno S.P., Knebel A., Johnson C., Hastie C.J., Gartner A.,
RA Gambus A., Labib K.;
RT "CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication
RT termination and mitosis.";
RL Nat. Cell Biol. 19:468-479(2017).
CC -!- FUNCTION: ATP-dependent chaperone which probably uses the energy
CC provided by ATP hydrolysis to generate mechanical force to unfold
CC substrate proteins, disassemble protein complexes, and disaggregate
CC protein aggregates (PubMed:18854144, PubMed:18782221, PubMed:22768338).
CC Can also prevent aggregation of unfolded proteins also in an ATP-
CC independent manner (PubMed:18782221). Targets polyubiquitinated
CC proteins for proteasomal degradation by binding to 'Lys-48'-linked
CC polyubiquitin chains (PubMed:19545544). Involved in the cytoplasmic
CC elimination of misfolded proteins exported from the ER
CC (PubMed:16647269, PubMed:17825049, PubMed:21317884, PubMed:22768338,
CC PubMed:25652260). This pathway, known as ERAD, prevents the activation
CC of the unfolded protein response (UPR) caused by the accumulation of
CC misfolded proteins in the ER (PubMed:16647269, PubMed:17825049,
CC PubMed:21317884, PubMed:22768338, PubMed:25652260). In association with
CC helicase him-6 and GTPase crp-1, regulates the unfolded protein
CC response (UPR) following ER stress, probably independently of the ERAD
CC pathway (PubMed:18458060). Together with udf-2 and chn-1, regulates
CC myosin assembly in body wall muscles by targeting myosin chaperone unc-
CC 45 for proteasomal degradation (PubMed:17369820). Together with the
CC ufd-1-npl-4 complex, controls the switch from spermatogenesis to
CC oogenesis by regulating E3 ligase cul-2 complex-mediated tra-1
CC proteasomal degradation (PubMed:19773360). During oocyte meiosis and
CC together with cdc-48.2, required for chromosome condensation at the
CC diakinesis phase in prophase I and for progression of metaphase I
CC (PubMed:17512499). During the first embryonic cell division, regulates
CC DNA replication and thus chromosome segregation and decondensation, and
CC nuclear envelope re-assembly (PubMed:18097415, PubMed:18854144,
CC PubMed:18728180, PubMed:21981920, PubMed:26842564, PubMed:28368371). In
CC S phase and in association with ufd-1, npl-4.1 and/or npl-4.2 and ubxn-
CC 3, ensures the degradation of DNA licensing factor cdt-1 after the
CC initiation of DNA replication and thus the disassembly of the DNA
CC replication CMG helicase complex by promoting the dissociation from
CC chromatin of several of its components including cdc-45 and sld-5
CC (PubMed:21981920, PubMed:26842564, PubMed:28368371). Regulates ubxn-3
CC nuclear localization during S phase (PubMed:26842564). During the first
CC embryonic cell divisions and together with cdc-48.2, regulates the re-
CC assembly of the nuclear envelope after mitosis possibly by inactivating
CC kinase air-2, a component of the chromosomal passenger complex (CPC)
CC (PubMed:18097415). However, in another study, cdc-48.1 does not appear
CC to be implicated in the regulation of air-2 (PubMed:18854144).
CC {ECO:0000269|PubMed:16647269, ECO:0000269|PubMed:17369820,
CC ECO:0000269|PubMed:17512499, ECO:0000269|PubMed:17825049,
CC ECO:0000269|PubMed:18097415, ECO:0000269|PubMed:18458060,
CC ECO:0000269|PubMed:18728180, ECO:0000269|PubMed:18782221,
CC ECO:0000269|PubMed:18854144, ECO:0000269|PubMed:19545544,
CC ECO:0000269|PubMed:19773360, ECO:0000269|PubMed:21317884,
CC ECO:0000269|PubMed:21981920, ECO:0000269|PubMed:22768338,
CC ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:26842564,
CC ECO:0000269|PubMed:28368371}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6;
CC Evidence={ECO:0000269|PubMed:18782221, ECO:0000269|PubMed:18854144,
CC ECO:0000269|PubMed:21454554};
CC -!- ACTIVITY REGULATION: The first ATP-binding region has low ATPase
CC activity (PubMed:21454554). The second ATP-binding region is
CC responsible for ATPase activity (PubMed:21454554). ATP binding to the
CC first ATP-binding region induces intrinsic activity of the second ATP-
CC binding region (PubMed:21454554). While ATP binding to the first ATP-
CC binding region appears to prevent ATP hydrolysis by the second ATP-
CC binding region, ADP-binding to first region promotes the coordinate and
CC cooperative ATPase cycle of the second ATP-binding region
CC (PubMed:21454554). ATP binding to the first ATP-binding region induces
CC a conformational change, promoting the rotation of the first ATP-
CC binding region relative to the second ATP-binding region in the hexamer
CC (PubMed:24055316). Inhibited by N-ethylmaleimide (NEM)
CC (PubMed:18782221). {ECO:0000269|PubMed:18782221,
CC ECO:0000269|PubMed:21454554, ECO:0000269|PubMed:24055316}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.39 mM for ATP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:21454554};
CC -!- SUBUNIT: Homohexamer; oligomerization is ATP-independent
CC (PubMed:18782221, PubMed:24055316). Forms a ring-shaped particle of
CC 18.3 nm diameter, that displays 6-fold radial symmetry
CC (PubMed:24055316). Interacts with cdc-48.2 and thus may form
CC heterohexamers (PubMed:16647269, PubMed:17369820, PubMed:25721663).
CC Forms a complex composed of cdc-48.1, him-6 and crp-1; within the
CC complex, interacts with helicase him-6 and GTPase crp-1
CC (PubMed:18458060). Forms a complex composed of deubiquitinating enzyme
CC atx-3, adapter ubxn-5 and cdc-48.1; within the complex, interacts (via
CC N-terminus) with ubxn-5 and with atx-3 (PubMed:19545544). Forms a
CC complex composed of deubiquitinating enzyme atx-3, E4 ubiquitin-protein
CC ligase ufd-2 and cdc-48.1; within the complex, interacts with atx-3 and
CC (via DDDLYN motif) with ufd-2 (PubMed:21317884, PubMed:27669035).
CC Interacts (via N-terminus) with atx-3 (via RRDR motif); the interaction
CC is not required for atx-3 enzymatic activity (PubMed:19545544,
CC PubMed:21317884). Forms a complex composed of cdc-48.1, myosin
CC chaperone unc-45, ubiquitin-protein ligases ufd-2 and chn-1; within the
CC complex, interacts (via DDDLYN motif) with ufd-2 and targets myosin
CC chaperone unc-45 for proteasomal degradation (PubMed:17369820,
CC PubMed:27669035). Forms a complex composed of ubxn-3, ufd-1, npl-4.1
CC and cdc-48.1; within the complex, interacts (via N-terminus) with ubxn-
CC 3 (via FPK motif) and with ufd-1 (PubMed:16647269, PubMed:20977550).
CC Forms a complex composed of ubxn-3, cdc-48.1 and/or cdc-48.2 and
CC substrate cdt-1 (PubMed:26842564). Interacts (via N-terminus) with
CC ubxn-1 (PubMed:16647269, PubMed:20977550). Interacts (via N-terminus)
CC with ubxn-2 (PubMed:23649807, PubMed:20977550). Interacts (via N-
CC terminus) with ubxn-4 (PubMed:20977550). Interacts with ubxn-6
CC (PubMed:20977550). Interacts with ufd-3 (PubMed:25721663). Does not
CC interact with air-2 (PubMed:18854144). {ECO:0000269|PubMed:16647269,
CC ECO:0000269|PubMed:17369820, ECO:0000269|PubMed:18458060,
CC ECO:0000269|PubMed:18782221, ECO:0000269|PubMed:18854144,
CC ECO:0000269|PubMed:19545544, ECO:0000269|PubMed:20977550,
CC ECO:0000269|PubMed:21317884, ECO:0000269|PubMed:23649807,
CC ECO:0000269|PubMed:24055316, ECO:0000269|PubMed:25721663,
CC ECO:0000269|PubMed:26842564, ECO:0000269|PubMed:27669035}.
CC -!- INTERACTION:
CC P54811; P54811: cdc-48.1; NbExp=2; IntAct=EBI-320245, EBI-320245;
CC P54811; P54812: cdc-48.2; NbExp=6; IntAct=EBI-320245, EBI-320265;
CC P54811; Q9TXH9: ubxn-1; NbExp=3; IntAct=EBI-320245, EBI-320236;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:20977550, ECO:0000269|PubMed:25721663}. Cytoplasm
CC {ECO:0000269|PubMed:17369820}. Note=Colocalizes with ubxn-1, ubxn-2 and
CC ubxn-3 to the perinuclear region in spermatocytes (PubMed:20977550).
CC Localizes to the perinuclear region in intestinal cells
CC (PubMed:25721663). {ECO:0000269|PubMed:20977550,
CC ECO:0000269|PubMed:25721663}.
CC -!- TISSUE SPECIFICITY: Expressed in germ cells and spermatheca
CC (PubMed:16701565). Expressed in body wall muscles (PubMed:17369820).
CC {ECO:0000269|PubMed:16701565, ECO:0000269|PubMed:17369820}.
CC -!- DEVELOPMENTAL STAGE: Expressed highly in embryos (at protein level)
CC (PubMed:16701565, PubMed:17369820). Expression decreases in larvae and
CC increases again in adults (at protein level) (PubMed:16701565,
CC PubMed:17369820). At the L4 larval stage, expressed in the proximal
CC gonad, predominantly at the pachytene stage and in spermatocytes
CC (PubMed:19773360). Not expressed in sperm (PubMed:19773360).
CC {ECO:0000269|PubMed:16701565, ECO:0000269|PubMed:17369820,
CC ECO:0000269|PubMed:19773360}.
CC -!- INDUCTION: Induced upon ER stress. Repressed by starvation and
CC oxidative stress. {ECO:0000269|PubMed:16701565}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes partial embryonic
CC lethality (PubMed:15716356, PubMed:18854144). Impairs response to ER
CC stress (PubMed:18458060). Abnormal accumulation of myosin chaperone
CC unc-45 in body wall muscles (PubMed:17369820). RNAi-mediated knockdown
CC in an unc-45 (m94) mutant background, restores motility
CC (PubMed:17369820). Simultaneous RNAi-mediated knockdown of cdc-48.2 in
CC embryos causes embryonic lethality (PubMed:15716356, PubMed:16647269,
CC PubMed:18097415, PubMed:18854144, PubMed:18728180). Defects in oocyte
CC meiosis I progression (PubMed:17512499). Defects in embryo S phase DNA
CC replication causing delays in cell cycle progression (PubMed:17512499,
CC PubMed:18728180, PubMed:21981920, PubMed:26842564, PubMed:28368371). At
CC the end of mitosis, impairs chromatin decondensation and nuclear
CC envelope re-assembly (PubMed:18728180, PubMed:18854144,
CC PubMed:18097415). In addition, abnormal accumulation of air-2 on
CC mitotic chromatin and impaired air-2 activation (PubMed:18097415). Does
CC not affect ER transition into sheet-like structures at the onset of
CC embryonic mitosis (PubMed:15716356). Simultaneous RNAi-mediated
CC knockdown of cdc-48.2 in young adults decreases lifespan, induces the
CC unfolded protein response, increases overall levels of
CC polyubiquitinated proteins, and impairs the degradation of misfolded ER
CC proteins (PubMed:16647269, PubMed:17825049, PubMed:17369820,
CC PubMed:21317884, PubMed:22768338). Causes defects in germline
CC development (PubMed:20977550). In an atx-3 (gk193) mutant background,
CC causes a 50 percent increase in longevity, a delay in age-related
CC muscle degeneration and resistance to oxidative and heat stresses
CC (PubMed:21317884). {ECO:0000269|PubMed:15716356,
CC ECO:0000269|PubMed:16647269, ECO:0000269|PubMed:17369820,
CC ECO:0000269|PubMed:17512499, ECO:0000269|PubMed:17825049,
CC ECO:0000269|PubMed:18097415, ECO:0000269|PubMed:18458060,
CC ECO:0000269|PubMed:18728180, ECO:0000269|PubMed:18854144,
CC ECO:0000269|PubMed:20977550, ECO:0000269|PubMed:21317884,
CC ECO:0000269|PubMed:21981920, ECO:0000269|PubMed:22768338,
CC ECO:0000269|PubMed:26842564, ECO:0000269|PubMed:28368371}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. CDC48 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: The role of cdc-48.1 in the regulation of kinase air-2, a
CC component of the chromosomal passenger complex (CPC), is controversial.
CC One study suggests that cdc-48.1 inactivates air-2 at the end of
CC mitosis whereas a second study shows that cdc-48.1 is not implicated in
CC the regulation of air-2. {ECO:0000269|PubMed:18097415,
CC ECO:0000269|PubMed:18854144}.
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DR EMBL; Z49886; CAA90050.1; -; Genomic_DNA.
DR PIR; T18970; T18970.
DR RefSeq; NP_496273.1; NM_063872.4.
DR AlphaFoldDB; P54811; -.
DR SMR; P54811; -.
DR BioGRID; 39940; 35.
DR DIP; DIP-26650N; -.
DR IntAct; P54811; 8.
DR STRING; 6239.C06A1.1; -.
DR EPD; P54811; -.
DR PaxDb; P54811; -.
DR PeptideAtlas; P54811; -.
DR EnsemblMetazoa; C06A1.1.1; C06A1.1.1; WBGene00007352.
DR GeneID; 174624; -.
DR KEGG; cel:CELE_C06A1.1; -.
DR UCSC; C06A1.1.1; c. elegans.
DR CTD; 174624; -.
DR WormBase; C06A1.1; CE02114; WBGene00007352; cdc-48.1.
DR eggNOG; KOG0730; Eukaryota.
DR GeneTree; ENSGT00970000196377; -.
DR HOGENOM; CLU_000688_12_3_1; -.
DR InParanoid; P54811; -.
DR OMA; ENFRFAQ; -.
DR OrthoDB; 194195at2759; -.
DR PhylomeDB; P54811; -.
DR PRO; PR:P54811; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00007352; Expressed in adult organism and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:WormBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IGI:WormBase.
DR GO; GO:0051228; P:mitotic spindle disassembly; IBA:GO_Central.
DR GO; GO:0045977; P:positive regulation of mitotic cell cycle, embryonic; IGI:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1905634; P:regulation of protein localization to chromatin; IGI:UniProtKB.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IBA:GO_Central.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR005938; AAA_ATPase_CDC48.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR004201; Cdc48_dom2.
DR InterPro; IPR029067; CDC48_domain_2-like_sf.
DR InterPro; IPR003338; CDC4_N-term_subdom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Vps4_C.
DR Pfam; PF00004; AAA; 2.
DR Pfam; PF17862; AAA_lid_3; 2.
DR Pfam; PF02933; CDC48_2; 1.
DR Pfam; PF02359; CDC48_N; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 2.
DR SMART; SM01072; CDC48_2; 1.
DR SMART; SM01073; CDC48_N; 1.
DR SUPFAM; SSF50692; SSF50692; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF54585; SSF54585; 1.
DR TIGRFAMs; TIGR01243; CDC48; 1.
DR PROSITE; PS00674; AAA; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Chaperone; Cytoplasm; Hydrolase; Nucleotide-binding;
KW Reference proteome; Repeat.
FT CHAIN 1..809
FT /note="Transitional endoplasmic reticulum ATPase homolog 1"
FT /id="PRO_0000084577"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 803..809
FT /note="Interaction with ufd-2"
FT /evidence="ECO:0000269|PubMed:17369820,
FT ECO:0000269|PubMed:21317884"
FT COMPBIAS 7..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 253..259
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 390
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 527..532
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MUTAGEN 257
FT /note="K->A: Loss of ATP binding. Complete loss of
FT catalytic activity. Complete loss of catalytic activity
FT without affecting oligomerization; when associated with A-
FT 365 and A-530."
FT /evidence="ECO:0000269|PubMed:18782221,
FT ECO:0000269|PubMed:21454554"
FT MUTAGEN 257
FT /note="K->T: Loss of ATP binding. Complete loss of
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 311
FT /note="E->D: Severe loss of ATP hydrolysis without
FT affecting ATP binding."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 311
FT /note="E->N,A: Severe loss of ATP hydrolysis without
FT affecting ATP binding and moderate reduction in
FT cooperativity between the 2 ATP-binding regions."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 311
FT /note="E->Q: Severe loss of ATP hydrolysis without
FT affecting ATP binding and loss of cooperativity between the
FT 2 ATP-binding regions. Slight reduction in catalytic
FT activity; when associated with A-354, A-365, A-467, S-467
FT or P-467. Complete loss of catalytic activity; when
FT associated with Q-584. Restores normal catalytic activity;
FT when associated with H-471."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 354
FT /note="N->A: Slight reduction in catalytic activity. Slight
FT reduction in catalytic activity; when associated with Q-
FT 311. Complete loss of catalytic activity; when associated
FT with A-631."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 365
FT /note="R->A: Slight reduction in catalytic activity. Slight
FT reduction in catalytic activity; when associated with Q-
FT 311. Complete loss of catalytic activity; when associated
FT with A-257 or A-642. Does not affect oligomerization; when
FT associated with A-257."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 467
FT /note="P->A,S: Slight reduction in catalytic activity; when
FT associated with Q-311."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 471
FT /note="R->H: Restores normal catalytic activity; when
FT associated with Q-311."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 530
FT /note="K->A: Loss of ATP binding and impaired rotation
FT between the two ATP-binding regions in the hexamer.
FT Complete loss of catalytic activity. Complete loss of
FT catalytic activity without affecting oligomerization; when
FT associated with A-257."
FT /evidence="ECO:0000269|PubMed:18782221,
FT ECO:0000269|PubMed:21454554, ECO:0000269|PubMed:24055316"
FT MUTAGEN 530
FT /note="K->T: Complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 584
FT /note="E->D: Severe loss of ATP hydrolysis without
FT affecting ATP binding."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 584
FT /note="E->Q: Severe loss of ATP hydrolysis without
FT affecting ATP binding. Does not affect rotation between the
FT 2 ATP-binding regions in the hexamer in presence of ATP or
FT ADP. Complete loss of catalytic activity; when associated
FT with Q-311."
FT /evidence="ECO:0000269|PubMed:21454554,
FT ECO:0000269|PubMed:24055316"
FT MUTAGEN 631
FT /note="N->A: Severe reduction in catalytic activity.
FT Complete loss of catalytic activity; when associated with
FT A-354."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 642
FT /note="R->A: Severe reduction in catalytic activity.
FT Complete loss of catalytic activity; when associated with
FT A-365."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 804..809
FT /note="Missing: Loss of interaction with ufd-2 but not with
FT atx-3."
FT /evidence="ECO:0000269|PubMed:17369820,
FT ECO:0000269|PubMed:21317884"
SQ SEQUENCE 809 AA; 89785 MW; ECF02EF8B939A777 CRC64;
MASVPTHQSE KEKKNDELST AILKDKVKPN RLIVDQSEQD DNSVIAVSQA KMDELGLFRG
DAVILKGKKR KESVAIIVSD ESCPNEKVRM NRVVRNNLRI RLGDVVSITP APNLSYGTRI
HVLPIDDTIE GLTGNLFDVF LKPYFLEAYR PLHKGDIFTV QAAMRTVEFK VVETEPAPAC
IVSPDTMIHY EGDPIKREEE EESMNDIGYD DLGGVRKQLA QIKEMVELPL RHPQLFKAIG
IKPPRGILLF GPPGTGKTLI ARAVANETGS FFFLINGPEV MSKMSGESES NLRKAFEECE
KNQPAILFID EIDAIAPKRE KTNGEVERRI VSQLLTLMDG VKGRSNLVVI AATNRPNSID
GALRRFGRFD REIDIGIPDA VGRLEILRIH TKNMKLADDV DLEQIANECH GFVGADLASL
CSEAALQQIR EKMELIDLED DQIDAEVLNS LAVTMENFRF AQGKSSPSAL REAVVETPNT
TWSDIGGLQN VKRELQELVQ YPVEHPEKYL KFGMQPSRGV LFYGPPGCGK TLLAKAIANE
CQANFISIKG PELLTMWFGE SEANVRDVFD KARAAAPCVL FFDELDSIAK ARGGGAGGDG
GGASDRVINQ VLTEMDGMNA KKNVFIIGAT NRPDIIDPAV LRPGRLDQLI YIPLPDEASR
HQILKASLRK TPLSKDLDLT FLAKNTVGFS GADLTEICQR ACKLAIRESI EKEIRIEKER
QDRQARGEEL MEDDAVDPVP EITRAHFEEA MKFARRSVTD NDIRKYEMFA QTLQQSRGFG
NNFKFPGEQR GSDAPSAPVP AQDDDDLYN
