ID PEX5_DEBHA Reviewed; 603 AA.
AC Q6BM14;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 27-MAR-2024, entry version 107.
DE RecName: Full=Peroxisomal targeting signal receptor;
DE Short=PTS1 receptor;
DE Short=PTS1R;
DE AltName: Full=Peroxin-5;
GN Name=PEX5; OrderedLocusNames=DEHA2F09108g;
OS Debaryomyces hansenii (strain ATCC 36239 / CBS 767 / BCRC 21394 / JCM 1990
OS / NBRC 0083 / IGC 2968) (Yeast) (Torulaspora hansenii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Debaryomyces.
OX NCBI_TaxID=284592;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 36239 / CBS 767 / BCRC 21394 / JCM 1990 / NBRC 0083 / IGC 2968;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
CC -!- FUNCTION: Receptor that mediates peroxisomal import of proteins
CC containing a C-terminal PTS1-type tripeptide peroxisomal targeting
CC signal (SKL-type). Binds to cargo proteins containing a PTS1
CC peroxisomal targeting signal in the cytosol, and translocates them into
CC the peroxisome matrix by passing through the PEX13-PEX14 docking
CC complex along with cargo proteins. PEX5 receptor is then
CC retrotranslocated into the cytosol, leading to release of bound cargo
CC in the peroxisome matrix, and reset for a subsequent peroxisome import
CC cycle. {ECO:0000250|UniProtKB:P35056}.
CC -!- SUBUNIT: Interacts (via WxxxF/Y and LVxEF motifs) with PEX14; promoting
CC translocation through the PEX13-PEX14 docking complex.
CC {ECO:0000250|UniProtKB:P35056}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P35056}. Peroxisome matrix
CC {ECO:0000250|UniProtKB:P35056}. Note=Cycles between the cytosol and the
CC peroxisome matrix. Following binding to cargo proteins containing a
CC PTS1 peroxisomal targeting signal in the cytosol, recruited to the
CC docking complex, composed of PEX13 and PEX14, leading to translocation
CC into the peroxisome matrix along with cargo proteins. Export and
CC recycling to the cytosol is initiated by binding to the PEX2-PEX10-
CC PEX12 ligase complex via its unstructured N-terminus that inserts into
CC the ligase pore and emerges in the cytosol. Cys-10 of PEX5 is then
CC monoubiquitinated, promoting its extraction from peroxisomal membrane
CC by the PEX1-PEX6 AAA ATPase complex (By similarity). Extraction is
CC accompanied by unfolding of the TPR repeats and release of bound cargo
CC in the peroxisome matrix (By similarity). The TPR repeats refold in the
CC cytosol and ubiquitination is removed by deubiquitinating enzyme UBP15,
CC resetting PEX5 for a subsequent import cycle (By similarity).
CC {ECO:0000250|UniProtKB:P35056, ECO:0000250|UniProtKB:P50542}.
CC -!- DOMAIN: The TPR repeats mediate interaction with proteins containing a
CC C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-
CC type). {ECO:0000250|UniProtKB:A0A1L8FDW4}.
CC -!- DOMAIN: The WxxxF/Y motifs mediate interaction with PEX14, promoting
CC association with the PEX13-PEX14 docking complex.
CC {ECO:0000250|UniProtKB:A0A1L8FDW4}.
CC -!- DOMAIN: The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are
CC required for PEX5 retrotranslocation and recycling. AH2 mediates
CC interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex,
CC while AH1 is required for extraction from peroxisomal membrane by the
CC PEX1-PEX6 AAA ATPase complex. {ECO:0000250|UniProtKB:A0A1L8FDW4}.
CC -!- PTM: Monoubiquitinated at Cys-10 by PEX2 during PEX5 passage through
CC the retrotranslocation channel: monoubiquitination acts as a signal for
CC PEX5 extraction and is required for proper export from peroxisomes and
CC recycling. When PEX5 recycling is compromised, polyubiquitinated at
CC Lys-22 by PEX10 during its passage through the retrotranslocation
CC channel, leading to its degradation. {ECO:0000250|UniProtKB:P35056}.
CC -!- SIMILARITY: Belongs to the peroxisomal targeting signal receptor
CC family. {ECO:0000305}.
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DR EMBL; CR382138; CAG89098.2; -; Genomic_DNA.
DR RefSeq; XP_460757.2; XM_460757.1.
DR AlphaFoldDB; Q6BM14; -.
DR SMR; Q6BM14; -.
DR STRING; 284592.Q6BM14; -.
DR GeneID; 2903774; -.
DR KEGG; dha:DEHA2F09108g; -.
DR VEuPathDB; FungiDB:DEHA2F09108g; -.
DR eggNOG; KOG1125; Eukaryota.
DR HOGENOM; CLU_013516_3_0_1; -.
DR InParanoid; Q6BM14; -.
DR OMA; WEEQFKQ; -.
DR OrthoDB; 2020042at2759; -.
DR Proteomes; UP000000599; Chromosome F.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005782; C:peroxisomal matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR InterPro; IPR024111; PEX5/PEX5L.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10130:SF0; GH08708P; 1.
DR PANTHER; PTHR10130; PEROXISOMAL TARGETING SIGNAL 1 RECEPTOR PEX5; 1.
DR Pfam; PF00515; TPR_1; 1.
DR SMART; SM00028; TPR; 4.
DR SUPFAM; SSF48452; TPR-like; 1.
DR PROSITE; PS50005; TPR; 4.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Isopeptide bond; Peroxisome; Protein transport;
KW Reference proteome; Repeat; Thioester bond; TPR repeat; Translocation;
KW Transport; Ubl conjugation.
FT CHAIN 1..603
FT /note="Peroxisomal targeting signal receptor"
FT /id="PRO_0000106310"
FT REPEAT 304..338
FT /note="TPR 1"
FT REPEAT 339..372
FT /note="TPR 2"
FT REPEAT 449..482
FT /note="TPR 3"
FT REPEAT 484..516
FT /note="TPR 4"
FT REPEAT 518..550
FT /note="TPR 5"
FT REGION 11..33
FT /note="Amphipathic helix 1 (AH1)"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT REGION 23..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..76
FT /note="Amphipathic helix 2 (AH2)"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT REGION 232..248
FT /note="Amphipathic helix 4 (AH4)"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT MOTIF 99..103
FT /note="WxxxF/Y motif 1"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT MOTIF 128..132
FT /note="WxxxF/Y motif 2"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT MOTIF 192..196
FT /note="WxxxF/Y motif 3"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT MOTIF 271..275
FT /note="WxxxF/Y motif 4"
FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4"
FT CROSSLNK 10
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P35056"
FT CROSSLNK 22
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P35056"
SQ SEQUENCE 603 AA; 68734 MW; F30230B4AAF68147 CRC64;
MSFVGGGADC SANSNAIAQF NKHTQQDRSL QRQAANQQGI VQNGQGFKKD SMMNERERQN
MDQFMNNGPS QSNFQFQPMR HELNMIQQNH KQPNVQNNWT NEFQTNSPSP VQRNTPLAKT
GSPANAQWAT EFQQPMDQTF NQSNQQQFNN MPNMRMGGYR PMMGMSMMGG GMHQQQNQMQ
HQEQNQDHQV DWDNQFKEIE QLTNETKDAE AEQVKGEEEP EIVIDDKYQA TFQEVWDSLN
SEEVENDFIN QQYEEFKNTQ RDSMPADMAQ WEKDFAKYAS TRAHFGDYQF EDNQHNQFLD
LPKESDPYEI GLQLMENGAK LSEAALAFEA AIQRNEGHIN AWLKLGEVQT QNEKEIAGIS
ALEKCLELHP ENSEALMTLA ISYINEGYDN AAFATLERWI STKYPQVADQ ARQQNPAIDD
EDRFSLNKRV TELFLNAAQL SPNSANMDPD VQMGLGVLFY ANEDFDKTID CFKAALSIKP
DDAVLWNRLG ASLANSNRSE EAVDAYFKAL ELKPTFVRAR YNLGVSCINI GCYKEAAEHL
LSGLSMHQVE GVQTDASSTL NHNQSTSLTE TLKRAFIALD RRDLLEKVKP DMDINQFRGE
FSF
//