ID PEX4_YEAST Reviewed; 183 AA. AC P29340; D6VUR5; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-1992, sequence version 1. DT 04-NOV-2026, entry version 201. DE RecName: Full=Ubiquitin-conjugating enzyme E2 PEX4 {ECO:0000305}; DE EC=2.3.2.23 {ECO:0000269|PubMed:17452527}; DE AltName: Full=E2 ubiquitin-conjugating enzyme PEX4; DE AltName: Full=Peroxin-4; DE AltName: Full=Ubiquitin carrier protein; DE AltName: Full=Ubiquitin-protein ligase; GN Name=PEX4; Synonyms=PAS2, UBC10; OrderedLocusNames=YGR133W; 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], AND SUBCELLULAR LOCATION. RX PubMed=1326082; DOI=10.1038/359073a0; RA Wiebel F.F., Kunau W.-H.; RT "The Pas2 protein essential for peroxisome biogenesis is related to RT ubiquitin-conjugating enzymes."; RL Nature 359:73-76(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; DOI=10.1038/387s081; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [5] RP FUNCTION. RX PubMed=17550898; DOI=10.1074/jbc.m702038200; RA Williams C., van den Berg M., Sprenger R.R., Distel B.; RT "A conserved cysteine is essential for Pex4p-dependent ubiquitination of RT the peroxisomal import receptor Pex5p."; RL J. Biol. Chem. 282:22534-22543(2007). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND RP MUTAGENESIS OF CYS-115. RX PubMed=17452527; DOI=10.1083/jcb.200611012; RA Platta H.W., El Magraoui F., Schlee D., Grunau S., Girzalsky W., RA Erdmann R.; RT "Ubiquitination of the peroxisomal import receptor Pex5p is required for RT its recycling."; RL J. Cell Biol. 177:197-204(2007). RN [7] RP FUNCTION. RX PubMed=18644345; DOI=10.1016/j.bbrc.2008.07.054; RA Williams C., van den Berg M., Geers E., Distel B.; RT "Pex10p functions as an E3 ligase for the Ubc4p-dependent ubiquitination of RT Pex5p."; RL Biochem. Biophys. Res. Commun. 374:620-624(2008). RN [8] {ECO:0007744|PDB:2Y9P} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH PEX22, AND INTERACTION WITH PEX22. RA Williams C., van den Berg M., Panjikar S., Distel B., Wilmanns M.; RT "Pex4P-Pex22P Structure."; RL Submitted (FEB-2011) to the PDB data bank. RN [9] {ECO:0007744|PDB:2Y9M} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH PEX22, FUNCTION, ACTIVITY REGULATION, RP INTERACTION WITH PEX22, AND MUTAGENESIS OF TYR-172. RX PubMed=22085930; DOI=10.1038/emboj.2011.411; RA Williams C., van den Berg M., Panjikar S., Stanley W.A., Distel B., RA Wilmanns M.; RT "Insights into ubiquitin-conjugating enzyme/ co-activator interactions from RT the structure of the Pex4p:Pex22p complex."; RL EMBO J. 31:391-402(2012). RN [10] {ECO:0007744|PDB:4BWF} RP X-RAY CRYSTALLOGRAPHY OF MUTANT 15-183 SER-105 AND SER-146 IN COMPLEX WITH RP PEX22, DISULFIDE BOND, AND MUTAGENESIS OF CYS-105 AND CYS-146. RX PubMed=23896733; DOI=10.1038/srep02212; RA Williams C., van den Berg M., Stanley W.A., Wilmanns M., Distel B.; RT "A disulphide bond in the E2 enzyme Pex4p modulates ubiquitin-conjugating RT activity."; RL Sci. Rep. 3:2212-2212(2013). CC -!- FUNCTION: E2 ubiquitin-conjugating enzyme involved in the CC ubiquitination of proteins associated with the peroxisomal membrane CC (PubMed:17452527, PubMed:17550898, PubMed:18644345, PubMed:22085930). CC Together with the peroxisomal retrotranslocation channel, involved in CC the monoubiquitination of the peroxisomal targeting signal receptor CC PEX5, targeting it for recycling to the cytosol (PubMed:17452527, CC PubMed:17550898, PubMed:18644345). May also be involved in the CC ubiquitination of PEX5 coreceptors (By similarity). CC {ECO:0000250|UniProtKB:P49428, ECO:0000269|PubMed:17452527, CC ECO:0000269|PubMed:17550898, ECO:0000269|PubMed:18644345, CC ECO:0000269|PubMed:22085930}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23; CC Evidence={ECO:0000269|PubMed:17452527}; CC -!- ACTIVITY REGULATION: Its catalytic activity is stimulated by PEX22. CC {ECO:0000269|PubMed:22085930}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:17452527}. CC -!- SUBUNIT: Interacts with PEX22 (via C-terminus); the interaction is CC direct and serves to anchor PEX4 at the peroxisomal membrane. CC {ECO:0000269|PubMed:22085930, ECO:0000269|Ref.8}. CC -!- INTERACTION: CC P29340; P39718: PEX22; NbExp=10; IntAct=EBI-19784, EBI-20707; CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:1326082}; CC Peripheral membrane protein {ECO:0000305|PubMed:1326082}; Cytoplasmic CC side {ECO:0000305|PubMed:1326082}. CC -!- DISRUPTION PHENOTYPE: Abolishes monoubiquitination of PEX5. CC {ECO:0000269|PubMed:17452527}. CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. CC {ECO:0000255|PROSITE-ProRule:PRU00388}. 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; X65470; CAA46467.1; -; Genomic_DNA. DR EMBL; Z72918; CAA97146.1; -; Genomic_DNA. DR EMBL; AY557776; AAS56102.1; -; Genomic_DNA. DR EMBL; BK006941; DAA08226.1; -; Genomic_DNA. DR PIR; S29088; S29088. DR RefSeq; NP_011649.1; NM_001181262.1. DR PDB; 2Y9M; X-ray; 2.60 A; A=15-183. DR PDB; 2Y9P; X-ray; 3.25 A; A=15-183. DR PDB; 4BWF; X-ray; 3.23 A; A=15-183. DR AlphaFoldDB; P29340; -. DR SMR; P29340; -. DR BioGRID; 33381; 207. DR DIP; DIP-4411N; -. DR FunCoup; P29340; 120. DR IntAct; P29340; 4. DR STRING; 4932.YGR133W; -. DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family. DR TCDB; 3.A.20.1.5; the peroxisomal protein importer (ppi) family. DR PaxDb; 4932-YGR133W; -. DR PeptideAtlas; P29340; -. DR EnsemblFungi; YGR133W_mRNA; YGR133W; YGR133W. DR GeneID; 853034; -. DR KEGG; sce:YGR133W; -. DR AGR; SGD:S000003365; -. DR SGD; S000003365; PEX4. DR VEuPathDB; FungiDB:YGR133W; -. DR eggNOG; KOG0417; Eukaryota. DR HOGENOM; CLU_030988_13_0_1; -. DR InParanoid; P29340; -. DR OMA; AAMYTME; -. DR OrthoDB; 9973183at2759; -. DR BioCyc; YEAST:G3O-30839-MONOMER; -. DR BRENDA; 2.3.2.23; 984. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 853034; 8 hits in 10 CRISPR screens. DR EvolutionaryTrace; P29340; -. DR PRO; PR:P29340; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P29340; protein. DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:SGD. DR GO; GO:0007031; P:peroxisome organization; IMP:SGD. DR GO; GO:0051865; P:protein autoubiquitination; IDA:SGD. DR GO; GO:0016562; P:protein import into peroxisome matrix, receptor recycling; IMP:SGD. DR GO; GO:0006513; P:protein monoubiquitination; IDA:SGD. DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central. DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB. DR CDD; cd23812; UBCc_ScPEX4-like; 1. DR FunFam; 3.10.110.10:FF:000096; Ubiquitin-conjugating enzyme E2-21 kDa; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR InterPro; IPR050113; Ub_conjugating_enzyme-E2-like. DR InterPro; IPR000608; UBC. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR PANTHER; PTHR24067; UBIQUITIN-CONJUGATING ENZYME E2; 1. DR Pfam; PF00179; UQ_con; 1. DR SMART; SM00212; UBCc; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS00183; UBC_1; 1. DR PROSITE; PS50127; UBC_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Disulfide bond; Membrane; Peroxisome; Peroxisome biogenesis; KW Reference proteome; Transferase; Ubl conjugation pathway. FT CHAIN 1..183 FT /note="Ubiquitin-conjugating enzyme E2 PEX4" FT /id="PRO_0000082558" FT DOMAIN 17..179 FT /note="UBC core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388" FT ACT_SITE 115 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388, FT ECO:0000255|PROSITE-ProRule:PRU10133" FT DISULFID 105..146 FT /evidence="ECO:0000269|PubMed:23896733, FT ECO:0007744|PDB:2Y9M" FT MUTAGEN 105 FT /note="C->S: Decreases enzyme activity; when associated FT with S-146." FT /evidence="ECO:0000269|PubMed:23896733" FT MUTAGEN 115 FT /note="C->S: Abolishes monoubiquitination of PEX5." FT /evidence="ECO:0000269|PubMed:17452527" FT MUTAGEN 146 FT /note="C->S: Decreases enzyme activity; when associated FT with S-105." FT /evidence="ECO:0000269|PubMed:23896733" FT MUTAGEN 172 FT /note="Y->A: Abolishes binding to PEX22 and decreases PEX4 FT activity." FT /evidence="ECO:0000269|PubMed:22085930" FT MUTAGEN 172 FT /note="Y->F: Decreases binding to PEX22." FT /evidence="ECO:0000269|PubMed:22085930" FT HELIX 16..33 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 38..40 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 42..46 FT /evidence="ECO:0007829|PDB:2Y9M" FT STRAND 47..54 FT /evidence="ECO:0007829|PDB:2Y9M" FT STRAND 60..66 FT /evidence="ECO:0007829|PDB:2Y9M" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:4BWF" FT TURN 72..75 FT /evidence="ECO:0007829|PDB:2Y9M" FT STRAND 77..83 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 86..90 FT /evidence="ECO:0007829|PDB:2Y9M" FT STRAND 94..97 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 109..112 FT /evidence="ECO:0007829|PDB:2Y9M" FT HELIX 117..119 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 121..123 FT /evidence="ECO:0007829|PDB:2Y9M" FT HELIX 130..142 FT /evidence="ECO:0007829|PDB:2Y9M" FT HELIX 152..158 FT /evidence="ECO:0007829|PDB:2Y9M" FT TURN 159..161 FT /evidence="ECO:0007829|PDB:2Y9M" FT HELIX 163..178 FT /evidence="ECO:0007829|PDB:2Y9M" SQ SEQUENCE 183 AA; 21118 MW; D4E438B689F76CAD CRC64; MPNFWILENR RSYTSDTCMS RIVKEYKVIL KTLASDDPIA NPYRGIIESL NPIDETDLSK WEAIISGPSD TPYENHQFRI LIEVPSSYPM NPPKISFMQN NILHCNVKSA TGEICLNILK PEEWTPVWDL LHCVHAVWRL LREPVCDSPL DVDIGNIIRC GDMSAYQGIV KYFLAERERI NNH //