ID PEX6_YEAST Reviewed; 1030 AA. AC P33760; D6W0L8; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 27-MAR-2024, entry version 192. DE RecName: Full=Peroxisomal ATPase PEX6 {ECO:0000305}; DE EC=3.6.4.- {ECO:0000269|PubMed:26066397, ECO:0000269|PubMed:26170309, ECO:0000269|PubMed:29321502}; DE AltName: Full=Peroxin-6 {ECO:0000305}; DE AltName: Full=Peroxisomal assembly protein 8 {ECO:0000303|PubMed:8241279}; GN Name=PEX6 {ECO:0000303|PubMed:12808025, ECO:0000312|SGD:S000005273}; GN Synonyms=PAS8 {ECO:0000303|PubMed:8241279}; OrderedLocusNames=YNL329C; GN ORFNames=N0310; 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=8241279; DOI=10.1016/0167-4781(93)90166-b; RA Voorn-Brouwer T., van der Leij I., Hemrika W., Distel B., Tabak H.F.; RT "Sequence of the PAS8 gene, the product of which is essential for RT biogenesis of peroxisomes in Saccharomyces cerevisiae."; RL Biochim. Biophys. Acta 1216:325-328(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=S288c / FY1676; RX PubMed=7645347; DOI=10.1002/yea.320110606; RA Maftahi M., Nicaud J.-M., Levesque H., Gaillardin C.; RT "Sequencing analysis of a 15.4 kb fragment of yeast chromosome XIV RT identifies the RPD3, PAS8 and KRE1 loci, five new open reading frames."; RL Yeast 11:567-572(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169873; RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F., RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its RT evolutionary implications."; RL Nature 387:93-98(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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 142-1030. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=8533474; DOI=10.1002/yea.320111010; RA van Dyck L., Pascual-Ahuir A., Purnelle B., Goffeau A.; RT "An 8.2 kb DNA segment from chromosome XIV carries the RPD3 and PAS8 genes RT as well as the Saccharomyces cerevisiae homologue of the thiamine-repressed RT nmt1 gene and a chromosome III-duplicated gene for a putative aryl-alcohol RT dehydrogenase."; RL Yeast 11:987-991(1995). RN [6] RP INTERACTION WITH PEX15, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-489; RP LYS-778 AND ASP-831. RX PubMed=12808025; DOI=10.1091/mbc.e02-11-0752; RA Birschmann I., Stroobants A.K., van den Berg M., Schaefer A., RA Rosenkranz K., Kunau W.-H., Tabak H.F.; RT "Pex15p of Saccharomyces cerevisiae provides a molecular basis for RT recruitment of the AAA peroxin Pex6p to peroxisomal membranes."; RL Mol. Biol. Cell 14:2226-2236(2003). RN [7] 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 [8] 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 [9] RP FUNCTION, INTERACTION WITH PEX1, AND MUTAGENESIS OF LYS-489; LYS-778 AND RP ASP-831. RX PubMed=15634331; DOI=10.1111/j.1432-1033.2004.04393.x; RA Birschmann I., Rosenkranz K., Erdmann R., Kunau W.-H.; RT "Structural and functional analysis of the interaction of the AAA-peroxins RT Pex1p and Pex6p."; RL FEBS J. 272:47-58(2005). RN [10] RP FUNCTION, INTERACTION WITH PEX1, AND MUTAGENESIS OF LYS-489; LYS-778 AND RP ASP-831. RX PubMed=16007078; DOI=10.1038/ncb1281; RA Platta H.W., Grunau S., Rosenkranz K., Girzalsky W., Erdmann R.; RT "Functional role of the AAA peroxins in dislocation of the cycling PTS1 RT receptor back to the cytosol."; RL Nat. Cell Biol. 7:817-822(2005). RN [11] RP FUNCTION. RX PubMed=16911527; DOI=10.1111/j.1742-4658.2006.05388.x; RA Rosenkranz K., Birschmann I., Grunau S., Girzalsky W., Kunau W.-H., RA Erdmann R.; RT "Functional association of the AAA complex and the peroxisomal RT importomer."; RL FEBS J. 273:3804-3815(2006). RN [12] RP INTERACTION WITH UBP15. RX PubMed=21665945; DOI=10.1074/jbc.m111.238600; RA Debelyy M.O., Platta H.W., Saffian D., Hensel A., Thoms S., Meyer H.E., RA Warscheid B., Girzalsky W., Erdmann R.; RT "Ubp15p, a ubiquitin hydrolase associated with the peroxisomal export RT machinery."; RL J. Biol. Chem. 286:28223-28234(2011). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PEX1, AND MUTAGENESIS OF RP LYS-778 AND GLU-832. RX PubMed=26170309; DOI=10.1073/pnas.1500257112; RA Blok N.B., Tan D., Wang R.Y., Penczek P.A., Baker D., DiMaio F., RA Rapoport T.A., Walz T.; RT "Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex RT revealed by cryo-electron microscopy."; RL Proc. Natl. Acad. Sci. U.S.A. 112:E4017-E4025(2015). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PEX1, AND MUTAGENESIS OF RP TYR-528; TYR-805 AND GLU-832. RX PubMed=26066397; DOI=10.1038/ncomms8331; RA Ciniawsky S., Grimm I., Saffian D., Girzalsky W., Erdmann R., Wendler P.; RT "Molecular snapshots of the Pex1/6 AAA+ complex in action."; RL Nat. Commun. 6:7331-7331(2015). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PEX1. RX PubMed=29321502; DOI=10.1038/s41467-017-02474-4; RA Gardner B.M., Castanzo D.T., Chowdhury S., Stjepanovic G., Stefely M.S., RA Hurley J.H., Lander G.C., Martin A.; RT "The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive RT threading."; RL Nat. Commun. 9:135-135(2018). CC -!- FUNCTION: Component of the PEX1-PEX6 AAA ATPase complex, a protein CC dislocase complex that mediates the ATP-dependent extraction of the CC PEX5 receptor from peroxisomal membranes, an essential step for PEX5 CC recycling (PubMed:15634331, PubMed:16007078, PubMed:16911527, CC PubMed:26170309, PubMed:26066397, PubMed:29321502). Specifically CC recognizes PEX5 monoubiquitinated at 'Cys-6', and pulls it out of the CC peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation CC channel (PubMed:26170309, PubMed:26066397, PubMed:29321502). Extraction CC by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the CC TPR repeats and release of bound cargo from PEX5 (PubMed:29321502). CC {ECO:0000269|PubMed:15634331, ECO:0000269|PubMed:16007078, CC ECO:0000269|PubMed:16911527, ECO:0000269|PubMed:26066397, CC ECO:0000269|PubMed:26170309, ECO:0000269|PubMed:29321502}. 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; CC Evidence={ECO:0000269|PubMed:26066397, ECO:0000269|PubMed:26170309, CC ECO:0000269|PubMed:29321502}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:26066397, ECO:0000269|PubMed:26170309, CC ECO:0000269|PubMed:29321502}; CC -!- SUBUNIT: Interacts with PEX1; forming the PEX1-PEX6 AAA ATPase complex, CC which is composed of a heterohexamer formed by a trimer of PEX1-PEX6 CC dimers (PubMed:15634331, PubMed:16007078, PubMed:26170309, CC PubMed:26066397, PubMed:29321502). Interacts with PEX15; anchors PEX1- CC PEX6 heterooligomers to the peroxisomal membrane and mediates their CC association with the peroxisomal importomer (PubMed:12808025). CC Interacts with UBP15 (PubMed:21665945). {ECO:0000269|PubMed:12808025, CC ECO:0000269|PubMed:15634331, ECO:0000269|PubMed:16007078, CC ECO:0000269|PubMed:21665945, ECO:0000269|PubMed:26066397, CC ECO:0000269|PubMed:26170309, ECO:0000269|PubMed:29321502}. CC -!- INTERACTION: CC P33760; P24004: PEX1; NbExp=16; IntAct=EBI-13178, EBI-13155; CC P33760; P53112: PEX14; NbExp=6; IntAct=EBI-13178, EBI-13212; CC P33760; Q08215: PEX15; NbExp=14; IntAct=EBI-13178, EBI-31849; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12808025}. CC Peroxisome membrane {ECO:0000269|PubMed:12808025, CC ECO:0000269|PubMed:14562095}; Peripheral membrane protein CC {ECO:0000269|PubMed:12808025}; Cytoplasmic side CC {ECO:0000269|PubMed:12808025}. Note=Associated with peroxisomal CC membranes; anchored by PEX15 to peroxisome membranes. CC {ECO:0000269|PubMed:12808025}. CC -!- DOMAIN: AAA-cassette D1 is required for interaction with PEX1. ATP- CC binding in AAA-cassette D1 is required for attachment to PEX15. ATP- CC binding and hydrolysis in AAA-cassette D2 is required for release from CC PEX15 and proper function in PEX5 dislocation. CC -!- MISCELLANEOUS: Present with 1630 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the AAA ATPase 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; L20789; AAA16574.1; -; Unassigned_DNA. DR EMBL; Z46259; CAA86369.1; -; Genomic_DNA. DR EMBL; Z71605; CAA96261.1; -; Genomic_DNA. DR EMBL; X83226; CAA58229.1; -; Genomic_DNA. DR EMBL; BK006947; DAA10234.1; -; Genomic_DNA. DR PIR; S43211; S43211. DR RefSeq; NP_014070.1; NM_001183167.1. DR PDB; 8C0V; EM; 4.10 A; B/D/F=1-1030. DR PDB; 8C0W; EM; 4.70 A; A/C/E=1-1030. DR PDB; 8U0X; X-ray; 1.86 A; A=1-184. DR PDBsum; 8C0V; -. DR PDBsum; 8C0W; -. DR PDBsum; 8U0X; -. DR AlphaFoldDB; P33760; -. DR EMDB; EMD-16372; -. DR EMDB; EMD-16373; -. DR EMDB; EMD-2582; -. DR EMDB; EMD-2583; -. DR EMDB; EMD-2584; -. DR EMDB; EMD-2585; -. DR EMDB; EMD-2586; -. DR EMDB; EMD-2587; -. DR EMDB; EMD-2588; -. DR EMDB; EMD-6253; -. DR EMDB; EMD-6254; -. DR EMDB; EMD-6255; -. DR EMDB; EMD-6359; -. DR EMDB; EMD-6360; -. DR SMR; P33760; -. DR BioGRID; 35512; 88. DR ComplexPortal; CPX-1901; Peroxisomal receptor export module complex. DR DIP; DIP-2621N; -. DR IntAct; P33760; 15. DR MINT; P33760; -. DR STRING; 4932.YNL329C; -. DR TCDB; 3.A.20.1.5; the peroxisomal protein importer (ppi) family. DR MaxQB; P33760; -. DR PaxDb; 4932-YNL329C; -. DR PeptideAtlas; P33760; -. DR EnsemblFungi; YNL329C_mRNA; YNL329C; YNL329C. DR GeneID; 855387; -. DR KEGG; sce:YNL329C; -. DR AGR; SGD:S000005273; -. DR SGD; S000005273; PEX6. DR VEuPathDB; FungiDB:YNL329C; -. DR eggNOG; KOG0736; Eukaryota. DR GeneTree; ENSGT00550000074953; -. DR HOGENOM; CLU_000688_0_4_1; -. DR InParanoid; P33760; -. DR OMA; DSMLNAM; -. DR OrthoDB; 7477at2759; -. DR BioCyc; YEAST:G3O-33313-MONOMER; -. DR BRENDA; 3.6.4.7; 984. DR BioGRID-ORCS; 855387; 0 hits in 10 CRISPR screens. DR PRO; PR:P33760; -. DR Proteomes; UP000002311; Chromosome XIV. DR RNAct; P33760; Protein. DR GO; GO:1904949; C:ATPase complex; IPI:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:SGD. DR GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central. DR GO; GO:0005777; C:peroxisome; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:SGD. DR GO; GO:0140318; F:protein transporter activity; IDA:UniProtKB. DR GO; GO:0016558; P:protein import into peroxisome matrix; IBA:GO_Central. DR GO; GO:0016562; P:protein import into peroxisome matrix, receptor recycling; IDA:UniProtKB. DR GO; GO:0043335; P:protein unfolding; IDA:UniProtKB. DR CDD; cd19527; RecA-like_PEX6_r2; 1. DR Gene3D; 1.10.8.60; -; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR003960; ATPase_AAA_CS. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR047533; RecA-like_PEX6_r2. DR PANTHER; PTHR23077; AAA-FAMILY ATPASE; 1. DR PANTHER; PTHR23077:SF9; PEROXISOME ASSEMBLY FACTOR 2; 1. DR Pfam; PF00004; AAA; 2. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00674; AAA; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cytoplasm; Hydrolase; Membrane; KW Nucleotide-binding; Peroxisome; Peroxisome biogenesis; Reference proteome. FT CHAIN 1..1030 FT /note="Peroxisomal ATPase PEX6" FT /id="PRO_0000084621" FT REGION 478..683 FT /note="AAA-cassette D1" FT REGION 767..956 FT /note="AAA-cassette D2" FT BINDING 772..779 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT MUTAGEN 489 FT /note="K->A: In PEX6pA1; decreased binding to PEX15." FT /evidence="ECO:0000269|PubMed:12808025, FT ECO:0000269|PubMed:15634331, ECO:0000269|PubMed:16007078" FT MUTAGEN 528 FT /note="Y->A: Cells are able to grow on a medium with oleate FT as a sole carbon source." FT /evidence="ECO:0000269|PubMed:26066397" FT MUTAGEN 778 FT /note="K->A: In PEX6pA2; increased amount of FT peroxisome-bound PEX6. Results in accumulation of PEX5 on FT peroxisomal membranes. In Amut mutant; abolished ATPase FT activity of the PEX1-PEX6 AAAATPase complex." FT /evidence="ECO:0000269|PubMed:12808025, FT ECO:0000269|PubMed:15634331, ECO:0000269|PubMed:16007078, FT ECO:0000269|PubMed:26170309" FT MUTAGEN 805 FT /note="Y->A: Cells are unable to grow on a medium with FT oleate as a sole carbon source." FT /evidence="ECO:0000269|PubMed:26066397" FT MUTAGEN 831 FT /note="D->Q: In PEX6pB2; increased amount of FT peroxisome-bound PEX6. Results in accumulation of PEX5 on FT peroxisomal membranes." FT /evidence="ECO:0000269|PubMed:12808025, FT ECO:0000269|PubMed:15634331, ECO:0000269|PubMed:16007078" FT MUTAGEN 832 FT /note="E->A: In Bmut mutant; abolished ATPase activity of FT the PEX1-PEX6 AAAATPase complex." FT /evidence="ECO:0000269|PubMed:26170309" FT MUTAGEN 832 FT /note="E->Q: Abolished ATP hydrolysis." FT /evidence="ECO:0000269|PubMed:26066397" SQ SEQUENCE 1030 AA; 115571 MW; 736FECB57BBFF8F8 CRC64; MKASLTFSLS GIYAPCSISR DIYLEYGDKK AECLYGTIRL PQYGPGCTPG KIVHCVLDDS LPFCSIVVPS KLFGFMPTQP TMDFCYFEPI LDNVVPVLDS VTFLINEQLY SKLMDLPQEM QQIQFLHYKY NINSMETVVH SRDILTSGLC QILNCSPFPQ GLVDFTETQL ILVNDTEQKL SALKYANEDE EYALPKIGTN SALSIDLESL PCTISRDLLR PAPHINDDNS IYAFTDAETL LRLDVTSGSF ITVSNMGCVR LVKLFVLLLP NGFKKRTIYA PPKIIASFPD CSVVTISKSN IGHTDIPIAN QVFISRVGGW LQSQKCFQNI ILTTLKKFFS ESKRILCQND LIPIAFDSSM ADLNIAEEND ESDDEDELGQ YYKNDSLVWF FVTSAELDCF SKDNSHFIID PNRTKLITTN ITNRRPLPLS RSNLQRYYGF AETFYYDLHI FPYVRQLVNI LETSFNCSQR GITLNASVLL HSTTNNVGKA TMVRFASKYL GIHLLEIDCL SLTSNSRQLD STSKIIGYIR AKCENVLPYA SPAVIFLAHL DSILLDVNAN QDPEAIKLQK SINFEMSKLL DDFTFKFPGT TFVGSVNNID NVPSSFRSHM RFEILVPVPS EAQRLRIFQW YLSSHELNRD VQQKVPVSYM DNISFSSLSS YSAGLTPLDI KSIVETARMT ATARFYQESK KCGWLPQSIL ITQEDLSKAT SKARNEFSVS IGAPQIPNVT WDDIGGIDFV KGEILDTIDM PLKHPELFTS GMKKRSGILF YGPPGTGKTL MAKAIATNFS LNFFSVKGPE LLNMYIGESE ANVRRVFQKA REAKPCVIFF DEIDSVAPKR GNQGDSGGVM DRIVSQLLAE LDGMSTDADG VFVIGATNRP DLLDEALLRP GRFDKLLYLG IPDTDTKQLN ILEALTRKFV LDNDVKLIEL AKLCPFNYTG ADFYALCSDA MLNAMSRIAR MVEKKVSQHN ELTGENISTR RWFDKIATKE DTKVVVKMED FLKAQEQLTP SVSRAELNHY EAVRANFEGA //