ID DOA1_YEAST Reviewed; 715 AA. AC P36037; D6VWZ0; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 202. DE RecName: Full=Protein DOA1 {ECO:0000303|PubMed:2111732}; DE AltName: Full=Degradation of alpha protein 1 {ECO:0000303|PubMed:2111732}; DE AltName: Full=Ubiquitin fusion degradation protein 3 {ECO:0000303|PubMed:7615550}; GN Name=DOA1 {ECO:0000303|PubMed:2111732, ECO:0000312|SGD:S000001696}; GN Synonyms=UFD3 {ECO:0000303|PubMed:7615550, GN ECO:0000312|SGD:S000001696}, ZZZ4 {ECO:0000312|SGD:S000001696}; GN OrderedLocusNames=YKL213C {ECO:0000312|SGD:S000001696}; 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]. RA Hochstrasser M., Gang G.; RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7941750; DOI=10.1002/yea.320100511; RA Tzermia M., Horaitis O., Alexandraki D.; RT "The complete sequencing of a 24.6 kb segment of yeast chromosome XI RT identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open RT reading frames including homologues to the threonine dehydratases, membrane RT transporters, hydantoinases and the phospholipase A2-activating protein."; RL Yeast 10:663-679(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8196765; DOI=10.1038/369371a0; RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A., RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., RA Becker I., Mewes H.-W.; RT "Complete DNA sequence of yeast chromosome XI."; RL Nature 369:371-378(1994). 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 PROTEIN SEQUENCE OF 126-144; 173-183; 215-227; 316-335; 345-361; 384-420; RP 534-541; 598-613; 654-685 AND 700-706, FUNCTION, AND INTERACTION WITH RP UBIQUITIN. RX PubMed=15096053; DOI=10.1021/bi035626r; RA Russell N.S., Wilkinson K.D.; RT "Identification of a novel 29-linked polyubiquitin binding protein, Ufd3, RT using polyubiquitin chain analogues."; RL Biochemistry 43:4844-4854(2004). RN [6] RP FUNCTION. RX PubMed=2111732; DOI=10.1016/0092-8674(90)90481-s; RA Hochstrasser M., Varshavsky A.; RT "In vivo degradation of a transcriptional regulator: the yeast alpha 2 RT repressor."; RL Cell 61:697-708(1990). RN [7] RP FUNCTION. RX PubMed=7615550; DOI=10.1074/jbc.270.29.17442; RA Johnson E.S., Ma P.C.M., Ota I.M., Varshavsky A.; RT "A proteolytic pathway that recognizes ubiquitin as a degradation signal."; RL J. Biol. Chem. 270:17442-17456(1995). RN [8] RP FUNCTION, INTERACTION WITH CDC48, AND MUTAGENESIS OF CYS-237. RX PubMed=8890162; DOI=10.1002/j.1460-2075.1996.tb00869.x; RA Ghislain M., Dohmen R.J., Levy F., Varshavsky A.; RT "Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin- RT mediated proteolysis in Saccharomyces cerevisiae."; RL EMBO J. 15:4884-4899(1996). RN [9] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [10] 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 [11] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH NPL4; UFD1; CDC48; OTU1 AND RP SHP1, INTERACTION WITH OTU1; UBIQUITIN AND CDC48, DOMAIN, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF 2-GLY--PHE-287; 2-GLY--SER-359; RP 2-GLY--MET-425; 426-SER--SER-715 AND 495-LYS--SER-715. 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 [12] RP FUNCTION, INTERACTION WITH UBIQUITIN AND CDC48, DOMAIN, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF 2-GLY--HIS-253; 2-GLY--LEU-253; PHE-417; RP 426-SER--SER-715; PHE-434 AND 451-ALA--SER-715. 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 [13] RP FUNCTION, INTERACTION WITH HSE1, SUBCELLULAR LOCATION, DOMAIN, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF 434-PHE--ASN-440 AND 434-PHE--SER-443. RX PubMed=18508771; DOI=10.1074/jbc.m802982200; RA Ren J., Pashkova N., Winistorfer S., Piper R.C.; RT "DOA1/UFD3 plays a role in sorting ubiquitinated membrane proteins into RT multivesicular bodies."; RL J. Biol. Chem. 283:21599-21611(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY RP 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY RP 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 [16] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH UBP3; BRE5 AND CDC48, AND RP INTERACTION WITH UBP3 AND CDC48. 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 [17] 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 [18] RP FUNCTION. RX PubMed=23525333; DOI=10.1534/genetics.113.149898; RA Au W.C., Dawson A.R., Rawson D.W., Taylor S.B., Baker R.E., Basrai M.A.; RT "A novel role of the N terminus of budding yeast histone H3 variant Cse4 in RT ubiquitin-mediated proteolysis."; RL Genetics 194:513-518(2013). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDC48 AND FZO1, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF ASP-15; PHE-222; TRP-265; PHE-417; PHE-434; RP ARG-541 AND ARG-669. 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 [20] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 464-715, FUNCTION, INTERACTION RP WITH CDC48, DOMAIN, ARM REPEATS, AND MUTAGENESIS OF ARG-541 AND ARG-669. 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 [21] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 354-715, AND ARM REPEATS. RX PubMed=21063153; RA Nishimasu R., Komori H., Higuchi Y., Nishimasu H., Hiroaki H.; RT "Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae RT Doa1/Ufd3."; RL Kobe J. Med. Sci. 56:E125-E139(2010). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 2-300, INTERACTION WITH RP UBIQUITIN, DOMAIN, AND MUTAGENESIS OF LEU-5; ASP-15; ALA-158; PHE-222; RP TRP-265 AND ASP-281. RX PubMed=21070969; DOI=10.1016/j.molcel.2010.10.018; RA Pashkova N., Gakhar L., Winistorfer S.C., Yu L., Ramaswamy S., Piper R.C.; RT "WD40 repeat propellers define a ubiquitin-binding domain that regulates RT turnover of F box proteins."; RL Mol. Cell 40:433-443(2010). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 325-715. RA Liu Y., Sun J.; RT "Crystal structure of PUL and PFU domain."; RL Submitted (DEC-2010) to the PDB data bank. CC -!- FUNCTION: Ubiquitin-binding protein involved in protein ubiquitination, CC sorting and degradation (PubMed:2111732, PubMed:8890162, CC PubMed:19805280, PubMed:18508771, PubMed:20508643, PubMed:27044889). CC Acts as a ubiquitinated substrate-recruiting adapter for chaperone CC ATPase CDC48 by binding mono- or polyubiquitin chains (PubMed:15096053, CC PubMed:16427015, PubMed:16428438, PubMed:27044889). Depending on the CC context, promotes or prevents proteasomal degradation of ubiquitinated CC proteins (PubMed:2111732, PubMed:8890162, PubMed:19805280, CC PubMed:27044889). Involved in the ubiquitin fusion degradation (UFD) CC pathway by promoting the degradation of ubiquitinated proteins CC (PubMed:2111732, PubMed:8890162, PubMed:19805280, PubMed:27044889). CC Involved in the mitochondria-associated degradation pathway (MAD) by CC promoting the degradation of several ubiquitinated membrane proteins CC (PubMed:27044889). By competing with UFD2 to bind CDC48, prevents the CC multi-ubiquitination and subsequent degradation of UFD2-dependent CC substrates (PubMed:16427015). Required for ribophagy, a process which CC relocalizes ribosomal particles into the vacuole for degradation in CC response to starvation (PubMed:20508643). Involved in the ubiquitin- CC mediated sorting of membrane proteins into multivesicular bodies (MVBs) CC (PubMed:18508771). In addition, plays an essential role in maintaining CC cellular ubiquitin levels (PubMed:7615550, PubMed:16427015, CC PubMed:16428438, PubMed:18508771, PubMed:19805280). May affect CC indirectly the degradation of ubiquitinylated proteins by regulating CC cellular ubiquitin levels (PubMed:7615550, PubMed:23525333). CC {ECO:0000269|PubMed:15096053, ECO:0000269|PubMed:16427015, CC ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:18508771, CC ECO:0000269|PubMed:19805280, ECO:0000269|PubMed:20508643, CC ECO:0000269|PubMed:2111732, ECO:0000269|PubMed:23525333, CC ECO:0000269|PubMed:27044889, ECO:0000269|PubMed:7615550, CC ECO:0000269|PubMed:8890162}. CC -!- SUBUNIT: Forms a complex composed of CDC48, NPL4, UFD1, DOA1, SHP1 and CC deubiquitinase OTU1; within the complex interacts with CDC48 CC (PubMed:16427015). Interacts (via PUL domain) with CDC48 (via C- CC terminus); the interaction is direct (PubMed:8890162, PubMed:16427015, CC PubMed:16428438, PubMed:27044889, PubMed:19805280, PubMed:20508643). CC Forms a complex composed of CDC48, DOA1, deubiquitinase UBP3 and CC probably BRE5; within the complex interacts with CDC48 and UBP3 CC (PubMed:20508643). May form a complex composed of VPS27, HSE1 and DOA1 CC (PubMed:18508771). Interacts with HSE1 (via SH3 domain) CC (PubMed:18508771). Interacts (via WD repeats and PFU domain) with CC ubiquitin; the interaction is direct (PubMed:15096053, PubMed:16427015, CC PubMed:16428438, PubMed:21070969). Interacts with ubiquitinated FZO1 CC but not unmodified FZO1; the interaction recruits FZO1 to CDC48 and CC promotes FZO1 proteasomal degradation (PubMed:27044889). CC {ECO:0000269|PubMed:15096053, ECO:0000269|PubMed:16427015, CC ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:18508771, CC ECO:0000269|PubMed:19805280, ECO:0000269|PubMed:20508643, CC ECO:0000269|PubMed:21070969, ECO:0000269|PubMed:27044889, CC ECO:0000269|PubMed:8890162}. CC -!- INTERACTION: CC P36037; P25694: CDC48; NbExp=6; IntAct=EBI-6017, EBI-4308; CC P36037; P38753: HSE1; NbExp=3; IntAct=EBI-6017, EBI-1382; CC P36037; Q01477: UBP3; NbExp=4; IntAct=EBI-6017, EBI-19834; CC P36037; Q01853: Vcp; Xeno; NbExp=2; IntAct=EBI-6017, EBI-80597; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095, CC ECO:0000269|PubMed:18508771, ECO:0000269|PubMed:27044889}. Cytoplasm CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:18508771, CC ECO:0000269|PubMed:27044889}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:27044889}; Peripheral membrane protein CC {ECO:0000269|PubMed:27044889}; Cytoplasmic side CC {ECO:0000269|PubMed:27044889}. Endosome membrane CC {ECO:0000269|PubMed:18508771}; Peripheral membrane protein CC {ECO:0000269|PubMed:18508771}; Cytoplasmic side CC {ECO:0000269|PubMed:18508771}. Note=Predominantly localizes to the CC cytoplasm. Probably localizes to endosomes and mitochondria in a CC transient manner. {ECO:0000269|PubMed:18508771, CC ECO:0000269|PubMed:27044889}. CC -!- DOMAIN: The WD repeats mediate interaction with ubiquitin. CC {ECO:0000269|PubMed:21070969}. CC -!- DOMAIN: The PUL domain is composed of 6 armadillo-like repeats and CC mediates the interaction with CDC48 C-terminus. CC {ECO:0000269|PubMed:16427015, ECO:0000269|PubMed:16428438, CC ECO:0000269|PubMed:19805280}. CC -!- DOMAIN: The PFU domain mediates interaction with ubiquitin. CC {ECO:0000269|PubMed:16428438, ECO:0000269|PubMed:18508771}. CC -!- DISRUPTION PHENOTYPE: Severely reduces cell growth in response to CC misfolded protein, translation inhibition-induced, heat or CC mitochondrial oxidative stresses but not in response to ER stress CC (PubMed:16427015, PubMed:18508771, PubMed:16428438, PubMed:27044889). CC {ECO:0000269|PubMed:16427015, ECO:0000269|PubMed:16428438, CC ECO:0000269|PubMed:18508771, ECO:0000269|PubMed:27044889}. CC -!- MISCELLANEOUS: Present with 6800 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the WD repeat PLAP family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U39947; AAA82258.1; -; Genomic_DNA. DR EMBL; X75951; CAA53560.1; -; Genomic_DNA. DR EMBL; Z28213; CAA82058.1; -; Genomic_DNA. DR EMBL; BK006944; DAA08956.1; -; Genomic_DNA. DR PIR; S38051; S38051. DR RefSeq; NP_012709.1; NM_001179778.1. DR PDB; 3GAE; X-ray; 1.60 A; A/B=464-715. DR PDB; 3L3F; X-ray; 1.90 A; X=354-715. DR PDB; 3ODT; X-ray; 1.35 A; A/B=2-300. DR PDB; 3PSP; X-ray; 2.42 A; A=325-715. DR PDB; 3PST; X-ray; 2.00 A; A=325-715. DR PDBsum; 3GAE; -. DR PDBsum; 3L3F; -. DR PDBsum; 3ODT; -. DR PDBsum; 3PSP; -. DR PDBsum; 3PST; -. DR AlphaFoldDB; P36037; -. DR SMR; P36037; -. DR BioGRID; 33952; 705. DR DIP; DIP-6274N; -. DR IntAct; P36037; 10. DR MINT; P36037; -. DR STRING; 4932.YKL213C; -. DR TCDB; 3.A.16.1.6; the endoplasmic reticular retrotranslocon (er-rt) family. DR GlyGen; P36037; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P36037; -. DR MaxQB; P36037; -. DR PaxDb; 4932-YKL213C; -. DR PeptideAtlas; P36037; -. DR EnsemblFungi; YKL213C_mRNA; YKL213C; YKL213C. DR GeneID; 853667; -. DR KEGG; sce:YKL213C; -. DR AGR; SGD:S000001696; -. DR SGD; S000001696; DOA1. DR VEuPathDB; FungiDB:YKL213C; -. DR eggNOG; KOG0301; Eukaryota. DR GeneTree; ENSGT00550000074944; -. DR HOGENOM; CLU_011791_2_0_1; -. DR InParanoid; P36037; -. DR OMA; WSKVGDV; -. DR OrthoDB; 1116432at2759; -. DR BioCyc; YEAST:G3O-31971-MONOMER; -. DR Reactome; R-SCE-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR BioGRID-ORCS; 853667; 0 hits in 10 CRISPR screens. DR EvolutionaryTrace; P36037; -. DR PRO; PR:P36037; -. DR Proteomes; UP000002311; Chromosome XI. DR RNAct; P36037; Protein. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IMP:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:SGD. DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IPI:UniProtKB. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:SGD. DR GO; GO:0072671; P:mitochondria-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:SGD. DR GO; GO:0034517; P:ribophagy; IMP:SGD. DR GO; GO:0010992; P:ubiquitin recycling; IMP:SGD. DR CDD; cd00200; WD40; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR Gene3D; 3.10.20.870; PFU (PLAA family ubiquitin binding), C-terminal domain; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015155; PFU. DR InterPro; IPR038122; PFU_sf. DR InterPro; IPR013535; PUL_dom. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR19849; PHOSPHOLIPASE A-2-ACTIVATING PROTEIN; 1. DR PANTHER; PTHR19849:SF0; PHOSPHOLIPASE A-2-ACTIVATING PROTEIN; 1. DR Pfam; PF09070; PFU; 1. DR Pfam; PF08324; PUL; 1. DR Pfam; PF00400; WD40; 6. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00320; WD40; 6. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS51394; PFU; 1. DR PROSITE; PS51396; PUL; 1. DR PROSITE; PS50082; WD_REPEATS_2; 4. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Direct protein sequencing; Endosome; Membrane; KW Mitochondrion; Mitochondrion outer membrane; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat. FT CHAIN 1..715 FT /note="Protein DOA1" FT /id="PRO_0000050958" FT REPEAT 11..40 FT /note="WD 1" FT /evidence="ECO:0000255" FT REPEAT 53..82 FT /note="WD 2" FT /evidence="ECO:0000255" FT REPEAT 97..125 FT /note="WD 3" FT /evidence="ECO:0000255" FT REPEAT 135..166 FT /note="WD 4" FT /evidence="ECO:0000255" FT REPEAT 177..206 FT /note="WD 5" FT /evidence="ECO:0000255" FT REPEAT 218..247 FT /note="WD 6" FT /evidence="ECO:0000255" FT REPEAT 259..288 FT /note="WD 7" FT /evidence="ECO:0000255" FT DOMAIN 352..449 FT /note="PFU" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00727" FT DOMAIN 465..715 FT /note="PUL" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00729" FT REPEAT 478..512 FT /note="ARM 1" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REPEAT 513..543 FT /note="ARM 2" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REPEAT 544..582 FT /note="ARM 3" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REPEAT 583..635 FT /note="ARM 4" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REPEAT 636..680 FT /note="ARM 5" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REPEAT 681..715 FT /note="ARM 6" FT /evidence="ECO:0000269|PubMed:21063153, FT ECO:0000305|PubMed:19805280" FT REGION 434..440 FT /note="Interaction with HSE1" FT /evidence="ECO:0000269|PubMed:18508771" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18407956, FT ECO:0007744|PubMed:19779198" FT MUTAGEN 2..425 FT /note="Missing: No binding to ubiquitin but does not affect FT the interaction with CDC48." FT /evidence="ECO:0000269|PubMed:16427015" FT MUTAGEN 2..359 FT /note="Missing: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16427015" FT MUTAGEN 2..353 FT /note="Missing: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16428438" FT MUTAGEN 2..330 FT /note="Missing: Does not affect binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16428438" FT MUTAGEN 2..287 FT /note="Missing: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16427015" FT MUTAGEN 5 FT /note="L->S: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:21070969" FT MUTAGEN 15 FT /note="D->S: No binding to ubiquitin. Reduces cell growth FT at high temperatures (37 degrees Celsius). Inhibits cell FT growth at high temperatures and prevents the degradation of FT mitochondrial proteins FZO1, MDM34 and MSP1 without FT affecting the interaction with CDC48 and UFD1; when FT associated with A-222 and A-265." FT /evidence="ECO:0000269|PubMed:21070969, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 158 FT /note="A->E: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:21070969" FT MUTAGEN 222 FT /note="F->A: No binding to ubiquitin. Inhibits cell growth FT at high temperatures and prevents the degradation of FT mitochondrial proteins FZO1, MDM34 and MSP1 without FT affecting the interaction with CDC48 and UFD1; when FT associated with S-15 and A-265." FT /evidence="ECO:0000269|PubMed:21070969, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 237 FT /note="C->Y: In ufd3-2; severe reduction in the degradation FT of short-lived ubiquitin-fusion proteins. No defect in the FT interaction with CDC48." FT /evidence="ECO:0000269|PubMed:8890162" FT MUTAGEN 265 FT /note="W->A: No binding to ubiquitin. Inhibits cell growth FT at high temperatures and prevents the degradation of FT mitochondrial proteins FZO1, MDM34 and MSP1 without FT affecting the interaction with CDC48 and UFD1; when FT associated with S-15 and A-222." FT /evidence="ECO:0000269|PubMed:21070969, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 281 FT /note="D->S: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:21070969" FT MUTAGEN 289..715 FT /note="Missing: No binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16427015" FT MUTAGEN 417 FT /note="F->D: Prevents binding to mono-ubiquitin, reduces FT levels of free ubiquitin, prevents the degradation of FT mitochondrial proteins FZO1, MDM34 and MSP1 and is FT partially sensitive to misfolded protein or translation FT inhibition-induced stresses; when associated with D-434." FT /evidence="ECO:0000269|PubMed:16428438, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 426..715 FT /note="Missing: No binding to ubiquitin and no interaction FT with CDC48." FT /evidence="ECO:0000269|PubMed:16427015, FT ECO:0000269|PubMed:16428438" FT MUTAGEN 434..443 FT /note="Missing: Loss of interaction with HSE1 and ubiquitin FT without affecting general ubquitination levels. Prevents FT protease CSP1 sorting into the vacuole." FT /evidence="ECO:0000269|PubMed:18508771" FT MUTAGEN 434..440 FT /note="FILKNTN->AAAKAAA: Loss of interaction with HSE1 FT without affecting binding to ubiquitin or general FT ubquitination levels. Prevents protease CSP1 sorting into FT the vacuole." FT /evidence="ECO:0000269|PubMed:18508771" FT MUTAGEN 434 FT /note="F->D: Prevents binding to mono-ubiquitin, reduces FT levels of free ubiquitin, prevents the degradation of FT mitochondrial proteins FZO1, MDM34 and MSP1 and is FT partially sensitive to misfolded protein or translation FT inhibition-induced stresses; when associated with D-417." FT /evidence="ECO:0000269|PubMed:16428438, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 451..715 FT /note="Missing: Does not affect binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16428438" FT MUTAGEN 495..715 FT /note="Missing: Loss of interaction with CDC48 without FT affecting binding to ubiquitin." FT /evidence="ECO:0000269|PubMed:16427015" FT MUTAGEN 541 FT /note="R->A: Depletion of cellular ubiquitin pools and FT reduced activity of the ubiquitin fusion degradation FT pathway. Prevents the interaction with CDC48 and UFD1 and FT thus the degradation of mitochondrial proteins FZO1, MDM34 FT and MSP1; when associated with A-669." FT /evidence="ECO:0000269|PubMed:19805280, FT ECO:0000269|PubMed:27044889" FT MUTAGEN 669 FT /note="R->A: Depletion of cellular ubiquitin pools and FT reduced activity of the ubiquitin fusion degradation FT pathway. Prevents the interaction with CDC48 and UFD1 and FT thus the degradation of mitochondrial proteins FZO1, MDM34 FT and MSP1; when associated with A-541." FT /evidence="ECO:0000269|PubMed:19805280, FT ECO:0000269|PubMed:27044889" FT CONFLICT 180 FT /note="D -> DI (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 4..9 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 16..23 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 26..31 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 34..52 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 57..63 FT /evidence="ECO:0007829|PDB:3ODT" FT TURN 64..67 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 68..73 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 78..82 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 119..125 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 128..134 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 140..147 FT /evidence="ECO:0007829|PDB:3ODT" FT TURN 148..151 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 152..157 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 162..166 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 169..174 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 182..189 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 192..197 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 200..206 FT /evidence="ECO:0007829|PDB:3ODT" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 212..217 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 223..228 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 234..238 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 241..246 FT /evidence="ECO:0007829|PDB:3ODT" FT TURN 248..250 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 253..258 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 264..269 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 275..279 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 284..289 FT /evidence="ECO:0007829|PDB:3ODT" FT HELIX 291..293 FT /evidence="ECO:0007829|PDB:3ODT" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:3L3F" FT STRAND 383..391 FT /evidence="ECO:0007829|PDB:3L3F" FT STRAND 400..404 FT /evidence="ECO:0007829|PDB:3L3F" FT HELIX 410..420 FT /evidence="ECO:0007829|PDB:3L3F" FT HELIX 425..427 FT /evidence="ECO:0007829|PDB:3L3F" FT HELIX 428..438 FT /evidence="ECO:0007829|PDB:3L3F" FT HELIX 480..494 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 499..509 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 512..529 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 534..543 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 544..546 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 550..553 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 554..560 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 566..579 FT /evidence="ECO:0007829|PDB:3GAE" FT TURN 583..585 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 586..590 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 593..596 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 599..602 FT /evidence="ECO:0007829|PDB:3GAE" FT STRAND 608..610 FT /evidence="ECO:0007829|PDB:3PSP" FT HELIX 612..634 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 642..651 FT /evidence="ECO:0007829|PDB:3GAE" FT TURN 652..656 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 658..662 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 664..680 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 682..685 FT /evidence="ECO:0007829|PDB:3GAE" FT TURN 688..690 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 692..701 FT /evidence="ECO:0007829|PDB:3GAE" FT HELIX 705..714 FT /evidence="ECO:0007829|PDB:3GAE" SQ SEQUENCE 715 AA; 79506 MW; 593B808169283B5F CRC64; MGYQLSATLK GHDQDVRDVV AVDDSKVASV SRDGTVRLWS KDDQWLGTVV YTGQGFLNSV CYDSEKELLL FGGKDTMING VPLFATSGED PLYTLIGHQG NVCSLSFQDG VVISGSWDKT AKVWKEGSLV YNLQAHNASV WDAKVVSFSE NKFLTASADK TIKLWQNDKV IKTFSGIHND VVRHLAVVDD GHFISCSNDG LIKLVDMHTG DVLRTYEGHE SFVYCIKLLP NGDIVSCGED RTVRIWSKEN GSLKQVITLP AISIWSVDCM SNGDIIVGSS DNLVRIFSQE KSRWASEDEI NELSTQVEKS TISSKTIEFD ESKLSPYEIL QSPGRKEGQI VVVKSPQGTI EAHQFSNSSW KKVGDVVGAG ATGNDKKIEF EGKTYDYVFD VDIEDGKPPL KLPINVSDNP YTAADNFLAR YELPMSYRDQ VVQFILKNTN GISLDQPNDN ASSSAVSPSK TSVMKVLPVK QYLIMENYNP DTIFNGIVKI NSNEKTFDDE ILAQIGGALH DIDESWELLL SFANTIRSNW EIKTPAYDIV RLIVKKLPYS SDIKDYIEEG LGNKNITLTM LTVRILVNCF NNENWGVKLL ESNQVYKSIF ETIDTEFSQA SAKQSQNLAI AVSTLIFNYS ALVTKGNSDL ELLPIVADAI NTKYGPLEEY QECEEAAYRL TVAYGNLATV EPTLRQFANS VTWLANIKRS YGNVPRFKDI FDDLS //