CDC48_YEAST
ID CDC48_YEAST Reviewed; 835 AA.
AC P25694; D6VRM4;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Cell division control protein 48 {ECO:0000305|PubMed:6749598};
DE EC=3.6.4.6 {ECO:0000269|PubMed:21454554};
DE AltName: Full=Cell division cycle protein 48 {ECO:0000303|PubMed:6749598};
DE AltName: Full=Transitional endoplasmic reticulum ATPase homolog {ECO:0000305};
GN Name=CDC48 {ECO:0000303|PubMed:6749598};
GN OrderedLocusNames=YDL126C {ECO:0000312|SGD:S000002284};
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1860879; DOI=10.1083/jcb.114.3.443;
RA Froehlich K.-U., Fries H.W., Ruediger M., Erdmann R., Botstein D.,
RA Mecke D.;
RT "Yeast cell cycle protein CDC48p shows full-length homology to the
RT mammalian protein VCP and is a member of a protein family involved in
RT secretion, peroxisome formation, and gene expression.";
RL J. Cell Biol. 114:443-453(1991).
RN [2]
RP SEQUENCE REVISION.
RA Froehlich K.-U.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP GENE NAME.
RX PubMed=6749598; DOI=10.1093/genetics/100.4.547;
RA Moir D., Stewart S.E., Osmond B.C., Botstein D.;
RT "Cold-sensitive cell-division-cycle mutants of yeast: isolation,
RT properties, and pseudoreversion studies.";
RL Genetics 100:547-563(1982).
RN [6]
RP FUNCTION, INTERACTION WITH NPL4, AND SUBCELLULAR LOCATION.
RX PubMed=11733065; DOI=10.1016/s0092-8674(01)00595-5;
RA Rape M., Hoppe T., Gorr I., Kalocay M., Richly H., Jentsch S.;
RT "Mobilization of processed, membrane-tethered SPT23 transcription factor by
RT CDC48(UFD1/NPL4), a ubiquitin-selective chaperone.";
RL Cell 107:667-677(2001).
RN [7]
RP INTERACTION WITH NPL4.
RX PubMed=11598205; DOI=10.1091/mbc.12.10.3226;
RA Hitchcock A.L., Krebber H., Frietze S., Lin A., Latterich M., Silver P.A.;
RT "The conserved npl4 protein complex mediates proteasome-dependent membrane-
RT bound transcription factor activation.";
RL Mol. Biol. Cell 12:3226-3241(2001).
RN [8]
RP FUNCTION.
RX PubMed=11813000; DOI=10.1038/ncb746;
RA Jarosch E., Taxis C., Volkwein C., Bordallo J., Finley D., Wolf D.H.,
RA Sommer T.;
RT "Protein dislocation from the ER requires polyubiquitination and the AAA-
RT ATPase Cdc48.";
RL Nat. Cell Biol. 4:134-139(2002).
RN [9]
RP FUNCTION.
RX PubMed=11740563; DOI=10.1038/414652a;
RA Ye Y., Meyer H.H., Rapoport T.A.;
RT "The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER
RT into the cytosol.";
RL Nature 414:652-656(2001).
RN [10]
RP FUNCTION.
RX PubMed=11847109; DOI=10.1093/emboj/21.4.615;
RA Braun S., Matuschewski K., Rape M., Thoms S., Jentsch S.;
RT "Role of the ubiquitin-selective CDC48(UFD1/NPL4) chaperone (segregase) in
RT ERAD of OLE1 and other substrates.";
RL EMBO J. 21:615-621(2002).
RN [11]
RP FUNCTION, AND INTERACTION WITH ASE1 AND CDC5.
RX PubMed=14636562; DOI=10.1016/s0092-8674(03)00815-8;
RA Cao K., Nakajima R., Meyer H.H., Zheng Y.;
RT "The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of
RT mitosis.";
RL Cell 115:355-367(2003).
RN [12]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [13]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-594 AND LYS-673, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [14]
RP INTERACTION WITH UBX PROTEINS.
RX PubMed=15258615; DOI=10.1038/sj.embor.7400203;
RA Schuberth C., Richly H., Rumpf S., Buchberger A.;
RT "Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent
RT protein degradation.";
RL EMBO Rep. 5:818-824(2004).
RN [15]
RP IDENTIFICATION IN CDC48-NPL4-UFD1 ATPASE COMPLEX, AND INTERACTION WITH HRD1
RP COMPLEX.
RX PubMed=16873066; DOI=10.1016/j.cell.2006.05.043;
RA Carvalho P., Goder V., Rapoport T.A.;
RT "Distinct ubiquitin-ligase complexes define convergent pathways for the
RT degradation of ER proteins.";
RL Cell 126:361-373(2006).
RN [16]
RP IDENTIFICATION IN A COMPLEX WITH NPL4; UFD1; SHP1 AND UFD2, IDENTIFICATION
RP IN A COMPLEX WITH NPL4; UFD1; SHP1; DOA1 AND OTU1, AND INTERACTION WITH
RP OTU1; UFD2 AND DOA1.
RX PubMed=16427015; DOI=10.1016/j.molcel.2005.12.014;
RA Rumpf S., Jentsch S.;
RT "Functional division of substrate processing cofactors of the ubiquitin-
RT selective Cdc48 chaperone.";
RL Mol. Cell 21:261-269(2006).
RN [17]
RP FUNCTION, AND INTERACTION WITH DOA1.
RX PubMed=16428438; DOI=10.1128/mcb.26.3.822-830.2006;
RA Mullally J.E., Chernova T., Wilkinson K.D.;
RT "Doa1 is a Cdc48 adapter that possesses a novel ubiquitin binding domain.";
RL Mol. Cell. Biol. 26:822-830(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-519 AND SER-770, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-770, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-472 AND THR-735, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [21]
RP INTERACTION WITH DOA1.
RX PubMed=19805280; DOI=10.1073/pnas.0908321106;
RA Zhao G., Li G., Schindelin H., Lennarz W.J.;
RT "An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in
RT ubiquitin homeostasis and protein degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16197-16202(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-519 AND THR-735, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [23]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH UBP3; BRE5 AND DOA1, AND
RP INTERACTION WITH UBP3 AND DOA1.
RX PubMed=20508643; DOI=10.1038/embor.2010.74;
RA Ossareh-Nazari B., Bonizec M., Cohen M., Dokudovskaya S., Delalande F.,
RA Schaeffer C., Van Dorsselaer A., Dargemont C.;
RT "Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required
RT for ribophagy.";
RL EMBO Rep. 11:548-554(2010).
RN [24]
RP FUNCTION, AND INTERACTION WITH VMS1.
RX PubMed=21070972; DOI=10.1016/j.molcel.2010.10.021;
RA Heo J.M., Livnat-Levanon N., Taylor E.B., Jones K.T., Dephoure N., Ring J.,
RA Xie J., Brodsky J.L., Madeo F., Gygi S.P., Ashrafi K., Glickman M.H.,
RA Rutter J.;
RT "A stress-responsive system for mitochondrial protein degradation.";
RL Mol. Cell 40:465-480(2010).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VMS1.
RX PubMed=21148305; DOI=10.1074/jbc.m110.179259;
RA Tran J.R., Tomsic L.R., Brodsky J.L.;
RT "A Cdc48p-associated factor modulates endoplasmic reticulum-associated
RT degradation, cell stress, and ubiquitinated protein homeostasis.";
RL J. Biol. Chem. 286:5744-5755(2011).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-261; GLU-315; ASN-358;
RP ARG-369; PRO-471; ARG-475; LYS-534; GLU-588 AND ARG-645.
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 [27]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23178123; DOI=10.1016/j.cell.2012.10.044;
RA Brandman O., Stewart-Ornstein J., Wong D., Larson A., Williams C.C.,
RA Li G.W., Zhou S., King D., Shen P.S., Weibezahn J., Dunn J.G., Rouskin S.,
RA Inada T., Frost A., Weissman J.S.;
RT "A ribosome-bound quality control complex triggers degradation of nascent
RT peptides and signals translation stress.";
RL Cell 151:1042-1054(2012).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [29]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-305; LYS-322; LYS-346; LYS-522
RP AND LYS-539, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [30]
RP SUBUNIT.
RX PubMed=23479637; DOI=10.1073/pnas.1221724110;
RA Defenouillere Q., Yao Y., Mouaikel J., Namane A., Galopier A., Decourty L.,
RA Doyen A., Malabat C., Saveanu C., Jacquier A., Fromont-Racine M.;
RT "Cdc48-associated complex bound to 60S particles is required for the
RT clearance of aberrant translation products.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:5046-5051(2013).
RN [31]
RP FUNCTION.
RX PubMed=24261871; DOI=10.1111/gtc.12106;
RA Matsuda R., Ikeuchi K., Nomura S., Inada T.;
RT "Protein quality control systems associated with no-go and nonstop mRNA
RT surveillance in yeast.";
RL Genes Cells 19:1-12(2014).
RN [32]
RP FUNCTION, AND INTERACTION WITH DOA1.
RX PubMed=27044889; DOI=10.1083/jcb.201510098;
RA Wu X., Li L., Jiang H.;
RT "Doa1 targets ubiquitinated substrates for mitochondria-associated
RT degradation.";
RL J. Cell Biol. 213:49-63(2016).
RN [33]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=29355480; DOI=10.7554/elife.33116;
RA Yang X., Arines F.M., Zhang W., Li M.;
RT "Sorting of a multi-subunit ubiquitin ligase complex in the endolysosome
RT system.";
RL Elife 7:0-0(2018).
RN [34]
RP FUNCTION.
RX PubMed=31445887; DOI=10.1016/j.molcel.2019.07.006;
RA Matsumoto S., Nakatsukasa K., Kakuta C., Tamura Y., Esaki M., Endo T.;
RT "Msp1 clears mistargeted proteins by facilitating their transfer from
RT mitochondria to the ER.";
RL Mol. Cell 76:191-205(2019).
RN [35] {ECO:0007744|PDB:6OA9, ECO:0007744|PDB:6OAA, ECO:0007744|PDB:6OAB}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.70 ANGSTROMS) IN COMPLEX WITH UFD1/NPL4
RP AND POLYUBIQUITINATED SUBSTRATE, AND FUNCTION.
RX PubMed=31249135; DOI=10.1126/science.aax1033;
RA Twomey E.C., Ji Z., Wales T.E., Bodnar N.O., Ficarro S.B., Marto J.A.,
RA Engen J.R., Rapoport T.A.;
RT "Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin
RT unfolding.";
RL Science 365:0-0(2019).
RN [36] {ECO:0007744|PDB:6OMB, ECO:0007744|PDB:6OPC}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.70 ANGSTROMS) IN COMPLEX WITH ADAPTER
RP SHP1 AND POLYUBIQUITINATED SUBSTRATE, AND FUNCTION.
RX PubMed=31249134; DOI=10.1126/science.aax0486;
RA Cooney I., Han H., Stewart M.G., Carson R.H., Hansen D.T., Iwasa J.H.,
RA Price J.C., Hill C.P., Shen P.S.;
RT "Structure of the Cdc48 segregase in the act of unfolding an authentic
RT substrate.";
RL Science 365:502-505(2019).
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:21454554, PubMed:31445887). By recruiting
CC and promoting the degradation of ubiquitinated proteins, plays a role
CC in the ubiquitin fusion degradation (UFD) pathway (PubMed:16428438).
CC Has a role in the endoplasmic reticulum-associated degradation (ERAD)
CC pathway which mediates the cytoplasmic elimination of misfolded
CC proteins exported from the ER (PubMed:11813000, PubMed:11740563,
CC PubMed:11847109, PubMed:21148305). Required for the proteasome-
CC dependent processing/activation of MGA2 and SPT23 transcription factors
CC leading to the subsequent expression of OLE1 (PubMed:11847109,
CC PubMed:11733065). Has an additional role in the turnover of OLE1 where
CC it targets ubiquitinated OLE1 and other proteins to the ERAD
CC (PubMed:11847109). Regulates ubiquitin-mediated mitochondria protein
CC degradation (PubMed:21070972, PubMed:27044889). Involved in spindle
CC disassembly probably by promoting the degradation of spindle assembly
CC factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562).
CC Component of the ribosome quality control complex (RQC), a ribosome-
CC associated complex that mediates ubiquitination and extraction of
CC incompletely synthesized nascent chains for proteasomal degradation
CC (PubMed:23178123, PubMed:24261871). CDC48 may provide the mechanical
CC force that dislodges the polyubiquitinated nascent peptides from the
CC exit channel (PubMed:23178123, PubMed:24261871). Required for
CC ribophagy, a process which relocalizes ribosomal particles into the
CC vacuole for degradation in response to starvation (PubMed:20508643).
CC Component of the DSC E3 ubiquitin ligase complexes that tag proteins
CC present in Golgi, endosome and vacuole membranes and function in
CC protein homeostasis under non-stress conditions and support a role in
CC protein quality control (PubMed:29355480). Substrate initially binds
CC through the attached polyubiquitin chain to UDF1/NPL4 and then moves
CC through the pore of the ATPase rings and is thereby unfolded
CC (PubMed:31249135, PubMed:31249134). Acts on a broad range of even well-
CC folded proteins via ubiquitin-binding and unfolding to initiate
CC substrate processing (PubMed:31249135). Involved in degradation of
CC mislocalized tail-anchored transmembrane proteins extracted from the
CC mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10
CC (PubMed:31445887). {ECO:0000269|PubMed:11733065,
CC ECO:0000269|PubMed:11740563, ECO:0000269|PubMed:11813000,
CC ECO:0000269|PubMed:11847109, ECO:0000269|PubMed:14636562,
CC ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:20508643,
CC ECO:0000269|PubMed:21070972, ECO:0000269|PubMed:21148305,
CC ECO:0000269|PubMed:21454554, ECO:0000269|PubMed:23178123,
CC ECO:0000269|PubMed:24261871, ECO:0000269|PubMed:27044889,
CC ECO:0000269|PubMed:29355480, ECO:0000269|PubMed:31249134,
CC ECO:0000269|PubMed:31249135, ECO:0000269|PubMed:31445887}.
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:21454554};
CC -!- ACTIVITY REGULATION: The first ATP-binding region has low ATPase
CC activity (By similarity). The second ATP-binding region is responsible
CC for ATPase activity (By similarity). ATP binding to the first ATP-
CC binding region induces intrinsic activity of the second ATP-binding
CC region (PubMed:21454554). While ATP binding to the first ATP-binding
CC region appears to prevent ATP hydrolysis by the second ATP-binding
CC region, ADP-binding to first region promotes the coordinate and
CC cooperative ATPase cycle of the second ATP-binding region (By
CC similarity). ATP binding to the first ATP-binding region induces a
CC conformational change, promoting the rotation of the first ATP-binding
CC region relative to the second ATP-binding region in the hexamer (By
CC similarity). {ECO:0000250|UniProtKB:P54811,
CC ECO:0000269|PubMed:21454554}.
CC -!- SUBUNIT: Component of the heterotrimeric CDC48-NPL4-UFD1 ATPase complex
CC (PubMed:16873066). The CDC48-NPL4-UFD1 ATPase complex interacts with
CC the HRD1 ubiquitin ligase complex composed of the E3 ligase HRD1, its
CC cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and
CC CDC48-binding protein UBX2 (PubMed:16873066). Interaction between the
CC complexes is mediated by interaction between CDC48-NPL4-UFD1 complex
CC member CDC48 and HRD1 complex member UBX2 (PubMed:16873066). Forms a
CC complex composed of CDC48, NPL4, UFD1, UFD2 and SHP1 (PubMed:16427015).
CC Forms a complex composed of CDC48, NPL4, UFD1, DOA1, SHP1 and
CC deubiquitinase OTU1; within the complex interacts with DOA1/UFD3 and
CC OTU1 to prevent multiubiquitination of substrates (PubMed:16427015).
CC Interacts with UFD2, to add further ubiquitin moieties; the interaction
CC with UFD2 is prevented by DOA1/UFD3 (PubMed:16427015). Forms a complex
CC composed of CDC48, DOA1, deubiquitinase UBP3 and probably BRE5; within
CC the complex interacts with DOA1 and UBP3 (PubMed:20508643). Interacts
CC (via C-terminus) with DOA1 (via PUL domain); the interaction is direct
CC (PubMed:16428438, PubMed:19805280, PubMed:27044889). Interacts with
CC NPL4 (PubMed:11733065, PubMed:11598205, PubMed:31249134). Interacts
CC with SHP1/UBX1, UBX2, UBX3, UBX4, UBX5, UBX6 and UBX7 (PubMed:15258615,
CC PubMed:31249134). Interacts with VMS1; the interaction recruits CDC48
CC to the mitochondria in response to mitochondrial stress
CC (PubMed:21070972, PubMed:21148305). Component of the ribosome quality
CC control complex (RQC), composed of the E3 ubiquitin ligase RKR1/LTN1,
CC RQC1 and RQC2, as well as CDC48 and its ubiquitin-binding cofactors
CC (PubMed:23178123, PubMed:23479637). RQC forms a stable complex with 60S
CC ribosomal subunits (PubMed:23178123, PubMed:23479637). Interacts with
CC ASE1 and CDC5; the interaction is likely to result in their degradation
CC (PubMed:14636562). Component of the DSCc E3 ligase complexes composed
CC of at least TUL1, DSC2, DSC3, UBX3, CDC48 as well as VLD1 for the
CC vacuole-localized complex or GLD1 for the Golgi/endosome-localized
CC complex (PubMed:29355480). {ECO:0000269|PubMed:11598205,
CC ECO:0000269|PubMed:11733065, ECO:0000269|PubMed:14636562,
CC ECO:0000269|PubMed:15258615, ECO:0000269|PubMed:16427015,
CC ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:16873066,
CC ECO:0000269|PubMed:19805280, ECO:0000269|PubMed:20508643,
CC ECO:0000269|PubMed:21070972, ECO:0000269|PubMed:21148305,
CC ECO:0000269|PubMed:23178123, ECO:0000269|PubMed:23479637,
CC ECO:0000269|PubMed:27044889, ECO:0000269|PubMed:29355480,
CC ECO:0000269|PubMed:31249134}.
CC -!- INTERACTION:
CC P25694; P53741: BRE5; NbExp=4; IntAct=EBI-4308, EBI-28528;
CC P25694; P25694: CDC48; NbExp=2; IntAct=EBI-4308, EBI-4308;
CC P25694; P38307: DER1; NbExp=5; IntAct=EBI-4308, EBI-5761;
CC P25694; P36037: DOA1; NbExp=6; IntAct=EBI-4308, EBI-6017;
CC P25694; Q08109: HRD1; NbExp=8; IntAct=EBI-4308, EBI-37613;
CC P25694; Q05787: HRD3; NbExp=6; IntAct=EBI-4308, EBI-31647;
CC P25694; P33755: NPL4; NbExp=11; IntAct=EBI-4308, EBI-12193;
CC P25694; P32628: RAD23; NbExp=2; IntAct=EBI-4308, EBI-14668;
CC P25694; P06778: RAD52; NbExp=4; IntAct=EBI-4308, EBI-14719;
CC P25694; P34223: SHP1; NbExp=10; IntAct=EBI-4308, EBI-17093;
CC P25694; Q12306: SMT3; NbExp=3; IntAct=EBI-4308, EBI-17490;
CC P25694; P40318: SSM4; NbExp=4; IntAct=EBI-4308, EBI-18208;
CC P25694; Q01477: UBP3; NbExp=4; IntAct=EBI-4308, EBI-19834;
CC P25694; Q04228: UBX2; NbExp=15; IntAct=EBI-4308, EBI-27730;
CC P25694; Q12229: UBX3; NbExp=3; IntAct=EBI-4308, EBI-35335;
CC P25694; P54730: UBX4; NbExp=5; IntAct=EBI-4308, EBI-28127;
CC P25694; Q06682: UBX5; NbExp=4; IntAct=EBI-4308, EBI-32041;
CC P25694; P47049: UBX6; NbExp=3; IntAct=EBI-4308, EBI-25866;
CC P25694; P38349: UBX7; NbExp=4; IntAct=EBI-4308, EBI-21157;
CC P25694; P53044: UFD1; NbExp=13; IntAct=EBI-4308, EBI-19997;
CC P25694; P54860: UFD2; NbExp=6; IntAct=EBI-4308, EBI-20003;
CC P25694; Q04311: VMS1; NbExp=5; IntAct=EBI-4308, EBI-784329;
CC -!- SUBCELLULAR LOCATION: Microsome {ECO:0000269|PubMed:11733065}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:21148305}. Cytoplasm
CC {ECO:0000269|PubMed:21148305}. Note=Bound loosely to components of the
CC microsomal fraction. {ECO:0000269|PubMed:11733065}.
CC -!- MISCELLANEOUS: Present with 78400 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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DR EMBL; X56956; CAA40276.1; -; Genomic_DNA.
DR EMBL; Z74174; CAA98694.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11734.1; -; Genomic_DNA.
DR PIR; S67669; S67669.
DR RefSeq; NP_010157.1; NM_001180185.1.
DR PDB; 6OA9; EM; 3.90 A; A/B/C/D/E/F=1-835.
DR PDB; 6OAA; EM; 4.10 A; B/C/D/E=1-835.
DR PDB; 6OAB; EM; 3.60 A; A/B/C/D/E=1-835.
DR PDB; 6OMB; EM; 3.70 A; A/B/C/D/E=1-835.
DR PDB; 6OPC; EM; 3.70 A; A/B/C/D/E/F=1-835.
DR PDBsum; 6OA9; -.
DR PDBsum; 6OAA; -.
DR PDBsum; 6OAB; -.
DR PDBsum; 6OMB; -.
DR PDBsum; 6OPC; -.
DR AlphaFoldDB; P25694; -.
DR SMR; P25694; -.
DR BioGRID; 31937; 926.
DR ComplexPortal; CPX-1323; CDC48-RAD23-UFD2 complex.
DR ComplexPortal; CPX-2946; CDC48-NPL4-UFD1 AAA ATPase complex.
DR ComplexPortal; CPX-3069; CDC48-NPL4-VMS1 AAA ATPase complex.
DR ComplexPortal; CPX-3265; Ribosome quality control complex.
DR DIP; DIP-2704N; -.
DR IntAct; P25694; 166.
DR MINT; P25694; -.
DR STRING; 4932.YDL126C; -.
DR TCDB; 3.A.16.1.2; the endoplasmic reticular retrotranslocon (er-rt) family.
DR CarbonylDB; P25694; -.
DR iPTMnet; P25694; -.
DR MaxQB; P25694; -.
DR PaxDb; P25694; -.
DR PRIDE; P25694; -.
DR EnsemblFungi; YDL126C_mRNA; YDL126C; YDL126C.
DR GeneID; 851431; -.
DR KEGG; sce:YDL126C; -.
DR SGD; S000002284; CDC48.
DR VEuPathDB; FungiDB:YDL126C; -.
DR eggNOG; KOG0730; Eukaryota.
DR GeneTree; ENSGT00940000165417; -.
DR HOGENOM; CLU_000688_12_2_1; -.
DR InParanoid; P25694; -.
DR OMA; HACHDIK; -.
DR BioCyc; YEAST:G3O-29525-MON; -.
DR Reactome; R-SCE-110320; Translesion Synthesis by POLH.
DR Reactome; R-SCE-3371511; HSF1 activation.
DR Reactome; R-SCE-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-SCE-5689896; Ovarian tumor domain proteases.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-8876725; Protein methylation.
DR Reactome; R-SCE-8951664; Neddylation.
DR Reactome; R-SCE-9755511; KEAP1-NFE2L2 pathway.
DR PRO; PR:P25694; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P25694; protein.
DR GO; GO:0036266; C:Cdc48p-Npl4p-Vms1p AAA ATPase complex; IDA:SGD.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0000837; C:Doa10p ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0000839; C:Hrd1p ubiquitin ligase ERAD-L complex; IDA:SGD.
DR GO; GO:0043332; C:mating projection tip; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0030894; C:replisome; IDA:SGD.
DR GO; GO:1990112; C:RQC complex; IDA:SGD.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
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:0019888; F:protein phosphatase regulator activity; IMP:SGD.
DR GO; GO:0043130; F:ubiquitin binding; IDA:SGD.
DR GO; GO:0046034; P:ATP metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097352; P:autophagosome maturation; IBA:GO_Central.
DR GO; GO:0071629; P:cytoplasm protein quality control by the ubiquitin-proteasome system; IMP:SGD.
DR GO; GO:0006274; P:DNA replication termination; IDA:SGD.
DR GO; GO:0016320; P:endoplasmic reticulum membrane fusion; IMP:SGD.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IDA:ComplexPortal.
DR GO; GO:0016236; P:macroautophagy; IMP:SGD.
DR GO; GO:0072671; P:mitochondria-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0051228; P:mitotic spindle disassembly; IMP:SGD.
DR GO; GO:0051974; P:negative regulation of telomerase activity; IMP:SGD.
DR GO; GO:0070651; P:nonfunctional rRNA decay; IMP:SGD.
DR GO; GO:0071630; P:nuclear protein quality control by the ubiquitin-proteasome system; IMP:SGD.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IMP:SGD.
DR GO; GO:2001168; P:positive regulation of histone H2B ubiquitination; IMP:SGD.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; IMP:SGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:SGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:SGD.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IC:ComplexPortal.
DR GO; GO:0043328; P:protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:SGD.
DR GO; GO:0032984; P:protein-containing complex disassembly; IMP:SGD.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IDA:SGD.
DR GO; GO:0034517; P:ribophagy; IMP:SGD.
DR GO; GO:1990116; P:ribosome-associated ubiquitin-dependent protein catabolic process; IMP:SGD.
DR GO; GO:1990171; P:SCF complex disassembly in response to cadmium stress; IMP:SGD.
DR GO; GO:0031134; P:sister chromatid biorientation; IMP:SGD.
DR GO; GO:0120174; P:stress-induced homeostatically regulated protein degradation pathway; IMP:SGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:ComplexPortal.
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 3D-structure; ATP-binding; Cell cycle; Chaperone; Cytoplasm;
KW Endoplasmic reticulum; Hydrolase; Isopeptide bond; Microsome;
KW Nucleotide-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; Transport; Ubl conjugation.
FT CHAIN 1..835
FT /note="Cell division control protein 48"
FT /id="PRO_0000084587"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 720..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 792..835
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 792..820
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 257..263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 358
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 531..536
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 735
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950"
FT CROSSLNK 305
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 346
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 522
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 539
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 594
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CROSSLNK 673
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT MUTAGEN 261
FT /note="K->A: Moderate reduction in growth rate."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 261
FT /note="K->T: Probable loss of ATP binding. Complete loss of
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 315
FT /note="E->A: Moderate reduction in growth rate."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 315
FT /note="E->D: Severe loss of catalytic activity without
FT affecting cooperativity between the 2 ATP-binding regions.
FT Slight reduction in growth rate."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 315
FT /note="E->N: Severe reduction in growth rate."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 315
FT /note="E->Q: Severe loss of catalytic activity and
FT cooperativity between the 2 ATP-binding regions. Lethal.
FT Restores cell growth; when associated with A-358; A-369; S-
FT 471; A-471 or H-475."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 358
FT /note="N->A: Slight reduction in growth rate. Restores cell
FT growth; when associated with Q-315."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 369
FT /note="R->A: No effect on growth rate. Restores cell
FT growth; when associated with Q-315."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 471
FT /note="P->A,S: Restores cell growth; when associated with
FT Q-315."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 475
FT /note="R->H: Restores cell growth; when associated with Q-
FT 315."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 534
FT /note="K->A,T: Severe loss of catalytic activity. Lethal."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 588
FT /note="E->D: Moderate reduction in growth rate."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 588
FT /note="E->Q: Lethal."
FT /evidence="ECO:0000269|PubMed:21454554"
FT MUTAGEN 645
FT /note="R->A: Lethal."
FT /evidence="ECO:0000269|PubMed:21454554"
SQ SEQUENCE 835 AA; 91996 MW; 02ADDB9A227614D8 CRC64;
MGEEHKPLLD ASGVDPREED KTATAILRRK KKDNMLLVDD AINDDNSVIA INSNTMDKLE
LFRGDTVLVK GKKRKDTVLI VLIDDELEDG ACRINRVVRN NLRIRLGDLV TIHPCPDIKY
ATRISVLPIA DTIEGITGNL FDVFLKPYFV EAYRPVRKGD HFVVRGGMRQ VEFKVVDVEP
EEYAVVAQDT IIHWEGEPIN REDEENNMNE VGYDDIGGCR KQMAQIREMV ELPLRHPQLF
KAIGIKPPRG VLMYGPPGTG KTLMARAVAN ETGAFFFLIN GPEVMSKMAG ESESNLRKAF
EEAEKNAPAI IFIDEIDSIA PKRDKTNGEV ERRVVSQLLT LMDGMKARSN VVVIAATNRP
NSIDPALRRF GRFDREVDIG IPDATGRLEV LRIHTKNMKL ADDVDLEALA AETHGYVGAD
IASLCSEAAM QQIREKMDLI DLDEDEIDAE VLDSLGVTMD NFRFALGNSN PSALRETVVE
SVNVTWDDVG GLDEIKEELK ETVEYPVLHP DQYTKFGLSP SKGVLFYGPP GTGKTLLAKA
VATEVSANFI SVKGPELLSM WYGESESNIR DIFDKARAAA PTVVFLDELD SIAKARGGSL
GDAGGASDRV VNQLLTEMDG MNAKKNVFVI GATNRPDQID PAILRPGRLD QLIYVPLPDE
NARLSILNAQ LRKTPLEPGL ELTAIAKATQ GFSGADLLYI VQRAAKYAIK DSIEAHRQHE
AEKEVKVEGE DVEMTDEGAK AEQEPEVDPV PYITKEHFAE AMKTAKRSVS DAELRRYEAY
SQQMKASRGQ FSNFNFNDAP LGTTATDNAN SNNSAPSGAG AAFGSNAEED DDLYS
