ID PEX5_HUMAN Reviewed; 639 AA. AC P50542; A8K891; B4DZ45; B7ZAD5; D3DUT8; Q15115; Q15266; Q96FN7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 3. DT 28-JUN-2023, entry version 222. DE RecName: Full=Peroxisomal targeting signal 1 receptor {ECO:0000305}; DE Short=PTS1 receptor {ECO:0000303|PubMed:7719337}; DE Short=PTS1R; DE AltName: Full=PTS1-BP; DE AltName: Full=Peroxin-5; DE AltName: Full=Peroxisomal C-terminal targeting signal import receptor; DE AltName: Full=Peroxisome receptor 1; GN Name=PEX5 {ECO:0000303|PubMed:10562279, ECO:0000312|HGNC:HGNC:9719}; GN Synonyms=PXR1 {ECO:0000303|PubMed:7719337}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INVOLVEMENT IN PBD2A, VARIANTS RP PBD2B 427-ARG--GLN-639 DEL AND LYS-526, FUNCTION, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RX PubMed=7719337; DOI=10.1038/ng0295-115; RA Dodt G., Braverman N., Wong C., Moser A., Moser H.W., Watkins P., Valle D., RA Gould S.J.; RT "Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 RT of the peroxisome biogenesis disorders."; RL Nat. Genet. 9:115-125(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=7790377; DOI=10.1083/jcb.130.1.51; RA Wiemer E.A.C., Nuttley W.M., Bertolaet B.L., Li X., Francke U., RA Wheelock M.J., Anne U.K., Johnson K.R., Subramani S.; RT "Human peroxisomal targeting signal-1 receptor restores peroxisomal protein RT import in cells from patients with fatal peroxisomal disorders."; RL J. Cell Biol. 130:51-65(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RC TISSUE=Liver; RX PubMed=7706321; DOI=10.1074/jbc.270.13.7731; RA Fransen M., Brees C., Baumgart E., Vanhooren J.C.T., Baes M., RA Mannaerts G.P., van Veldhoven P.P.; RT "Identification and characterization of the putative human peroxisomal C- RT terminal targeting signal import receptor."; RL J. Biol. Chem. 270:7731-7736(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION (ISOFORM 1), AND CHARACTERIZATION OF VARIANTS PBD2B RP 427-ARG--GLN-639 DEL AND LYS-526. RX PubMed=9668159; DOI=10.1093/hmg/7.8.1195; RA Braverman N., Dodt G., Gould S.J., Valle D.; RT "An isoform of pex5p, the human PTS1 receptor, is required for the import RT of PTS2 proteins into peroxisomes."; RL Hum. Mol. Genet. 7:1195-1205(1998). RN [9] RP INTERACTION WITH PEX12. RX PubMed=10562279; DOI=10.1083/jcb.147.4.761; RA Chang C.C., Warren D.S., Sacksteder K.A., Gould S.J.; RT "PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor RT docking in peroxisomal matrix protein import."; RL J. Cell Biol. 147:761-774(1999). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11336669; DOI=10.1016/s0092-8674(01)00310-5; RA Dammai V., Subramani S.; RT "The human peroxisomal targeting signal receptor, Pex5p, is translocated RT into the peroxisomal matrix and recycled to the cytosol."; RL Cell 105:187-196(2001). RN [11] RP INTERACTION WITH PEX14, DOMAIN, WXXXF/Y MOTIFS, AND MUTAGENESIS OF TRP-118 RP AND PHE-122. RX PubMed=11438541; DOI=10.1074/jbc.m104647200; RA Saidowsky J., Dodt G., Kirchberg K., Wegner A., Nastainczyk W., RA Kunau W.-H., Schliebs W.; RT "The di-aromatic pentapeptide repeats of the human peroxisome import RT receptor PEX5 are separate high affinity binding sites for the peroxisomal RT membrane protein PEX14."; RL J. Biol. Chem. 276:34524-34529(2001). RN [12] RP FUNCTION (ISOFORM 1), SUBCELLULAR LOCATION, AND INTERACTION WITH PEX7 RP (ISOFORM 1). RX PubMed=11546814; DOI=10.1074/jbc.m106932200; RA Dodt G., Warren D., Becker E., Rehling P., Gould S.J.; RT "Domain mapping of human PEX5 reveals functional and structural RT similarities to Saccharomyces cerevisiae Pex18p and Pex21p."; RL J. Biol. Chem. 276:41769-41781(2001). RN [13] RP FUNCTION. RX PubMed=12456682; DOI=10.1074/jbc.m206651200; RA Harper C.C., Berg J.M., Gould S.J.; RT "PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12."; RL J. Biol. Chem. 278:7897-7901(2003). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16314507; DOI=10.1128/mcb.25.24.10822-10832.2005; RA Miyata N., Fujiki Y.; RT "Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: RT ATP-independent import and ATP-dependent export."; RL Mol. Cell. Biol. 25:10822-10832(2005). RN [15] RP SUBCELLULAR LOCATION, UBIQUITINATION AT CYS-11, AND MUTAGENESIS OF CYS-11. RX PubMed=19208625; DOI=10.1074/jbc.m808978200; RA Grou C.P., Carvalho A.F., Pinto M.P., Huybrechts S.J., Sa-Miranda C., RA Fransen M., Azevedo J.E.; RT "Properties of the ubiquitin-pex5p thiol ester conjugate."; RL J. Biol. Chem. 284:10504-10513(2009). RN [16] RP FUNCTION, AND INTERACTION WITH PEX14. RX PubMed=21976670; DOI=10.1074/jbc.m111.287201; RA Freitas M.O., Francisco T., Rodrigues T.A., Alencastre I.S., Pinto M.P., RA Grou C.P., Carvalho A.F., Fransen M., Sa-Miranda C., Azevedo J.E.; RT "PEX5 protein binds monomeric catalase blocking its tetramerization and RT releases it upon binding the N-terminal domain of PEX14."; RL J. Biol. Chem. 286:40509-40519(2011). RN [17] RP DEUBIQUITINATION AT CYS-11, AND MUTAGENESIS OF CYS-11. RX PubMed=22371489; DOI=10.1074/jbc.m112.340158; RA Grou C.P., Francisco T., Rodrigues T.A., Freitas M.O., Pinto M.P., RA Carvalho A.F., Domingues P., Wood S.A., Rodriguez-Borges J.E., RA Sa-Miranda C., Fransen M., Azevedo J.E.; RT "Identification of ubiquitin-specific protease 9X (USP9X) as a RT deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate."; RL J. Biol. Chem. 287:12815-12827(2012). RN [18] RP INTERACTION WITH ZFAND6. RX PubMed=21980954; DOI=10.1111/j.1600-0854.2011.01298.x; RA Miyata N., Okumoto K., Mukai S., Noguchi M., Fujiki Y.; RT "AWP1/ZFAND6 functions in Pex5 export by interacting with cys- RT monoubiquitinated Pex5 and Pex6 AAA ATPase."; RL Traffic 13:168-183(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT CYS-11 AND LYS-527, AND RP MUTAGENESIS OF LYS-527. RX PubMed=24662292; DOI=10.1074/jbc.m113.527937; RA Okumoto K., Noda H., Fujiki Y.; RT "Distinct modes of ubiquitination of peroxisome-targeting signal type 1 RT (PTS1) receptor Pex5p regulate PTS1 protein import."; RL J. Biol. Chem. 289:14089-14108(2014). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115; SER-153; SER-155; RP SER-167 AND SER-279, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, UBIQUITINATION AT CYS-11, AND RP MUTAGENESIS OF CYS-11. RX PubMed=24118911; DOI=10.1111/tra.12129; RA Apanasets O., Grou C.P., Van Veldhoven P.P., Brees C., Wang B., RA Nordgren M., Dodt G., Azevedo J.E., Fransen M.; RT "PEX5, the shuttling import receptor for peroxisomal matrix proteins, is a RT redox-sensitive protein."; RL Traffic 15:94-103(2014). RN [23] RP FUNCTION (ISOFORM 1), AND INTERACTION WITH PEX7 (ISOFORM 1). RX PubMed=25538232; DOI=10.1074/jbc.m114.601575; RA Kunze M., Malkani N., Maurer-Stroh S., Wiesinger C., Schmid J.A., RA Berger J.; RT "Mechanistic insights into PTS2-mediated peroxisomal protein import: the RT co-receptor PEX5L drastically increases the interaction strength between RT the cargo protein and the receptor PEX7."; RL J. Biol. Chem. 290:4928-4940(2015). RN [24] RP INVOLVEMENT IN RCDP5. RX PubMed=26220973; DOI=10.1093/hmg/ddv305; RA Baroey T., Koster J., Stroemme P., Ebberink M.S., Misceo D., RA Ferdinandusse S., Holmgren A., Hughes T., Merckoll E., Westvik J., RA Woldseth B., Walter J., Wood N., Tvedt B., Stadskleiv K., Wanders R.J., RA Waterham H.R., Frengen E.; RT "A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by RT loss of the PEX5 long isoform."; RL Hum. Mol. Genet. 24:5845-5854(2015). RN [25] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SQSTM1, PHOSPHORYLATION AT RP SER-141, UBIQUITINATION AT LYS-209, AND MUTAGENESIS OF SER-141 AND LYS-209. RX PubMed=26344566; DOI=10.1038/ncb3230; RA Zhang J., Tripathi D.N., Jing J., Alexander A., Kim J., Powell R.T., RA Dere R., Tait-Mulder J., Lee J.H., Paull T.T., Pandita R.K., Charaka V.K., RA Pandita T.K., Kastan M.B., Walker C.L.; RT "ATM functions at the peroxisome to induce pexophagy in response to ROS."; RL Nat. Cell Biol. 17:1259-1269(2015). RN [26] RP UBIQUITINATION. RX PubMed=27597759; DOI=10.1083/jcb.201511034; RA Sargent G., van Zutphen T., Shatseva T., Zhang L., Di Giovanni V., RA Bandsma R., Kim P.K.; RT "PEX2 is the E3 ubiquitin ligase required for pexophagy during RT starvation."; RL J. Cell Biol. 214:677-690(2016). RN [27] RP INTERACTION WITH PEX14, AND MUTAGENESIS OF CYS-11. RX PubMed=28765278; DOI=10.1074/jbc.m117.805044; RA Dias A.F., Rodrigues T.A., Pedrosa A.G., Barros-Barbosa A., Francisco T., RA Azevedo J.E.; RT "The peroxisomal matrix protein translocon is a large cavity-forming RT protein assembly into which PEX5 protein enters to release its cargo."; RL J. Biol. Chem. 292:15287-15300(2017). RN [28] RP UBIQUITINATION AT LYS-472, AND MUTAGENESIS OF CYS-11; LYS-209; LYS-472 AND RP LYS-527. RX PubMed=28724525; DOI=10.1083/jcb.201611170; RA Wang W., Xia Z.J., Farre J.C., Subramani S.; RT "TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein RT import."; RL J. Cell Biol. 216:2843-2858(2017). RN [29] RP UBIQUITINATION AT CYS-11, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-11. RX PubMed=29884772; DOI=10.1074/jbc.ra118.003669; RA Pedrosa A.G., Francisco T., Bicho D., Dias A.F., Barros-Barbosa A., RA Hagmann V., Dodt G., Rodrigues T.A., Azevedo J.E.; RT "Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and RT PEX6 and is unfolded during its dislocation into the cytosol."; RL J. Biol. Chem. 293:11553-11563(2018). RN [30] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PEX7, VARIANT SER-218, AND RP CHARACTERIZATION OF VARIANT SER-218. RX PubMed=33389129; DOI=10.1007/s00439-020-02238-z; RA Ali M., Khan S.Y., Rodrigues T.A., Francisco T., Jiao X., Qi H., Kabir F., RA Irum B., Rauf B., Khan A.A., Mehmood A., Naeem M.A., Assir M.Z., Ali M.H., RA Shahzad M., Abu-Amero K.K., Akram S.J., Akram J., Riazuddin S., RA Riazuddin S., Robinson M.L., Baes M., Azevedo J.E., Hejtmancik J.F., RA Riazuddin S.A.; RT "A missense allele of PEX5 is responsible for the defective import of PTS2 RT cargo proteins into peroxisomes."; RL Hum. Genet. 140:649-666(2021). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 272-639 IN COMPLEX WITH TARGETING RP PEPTIDE, FUNCTION, AND DOMAIN. RX PubMed=11101887; DOI=10.1038/81930; RA Gatto G.J. Jr., Geisbrecht B.V., Gould S.J., Berg J.M.; RT "Peroxisomal targeting signal-1 recognition by the TPR domains of human RT PEX5."; RL Nat. Struct. Biol. 7:1091-1095(2000). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 321-639 IN COMPLEX WITH TARGETING RP PEPTIDE, FUNCTION, AND DOMAIN. RX PubMed=17157249; DOI=10.1016/j.molcel.2006.10.024; RA Stanley W.A., Filipp F.V., Kursula P., Schueller N., Erdmann R., RA Schliebs W., Sattler M., Wilmanns M.; RT "Recognition of a functional peroxisome type 1 target by the dynamic import RT receptor Pex5p."; RL Mol. Cell 24:653-663(2006). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 315-639, BINDING TO C-TERMINAL RP TARGETING PEPTIDES, AND FUNCTION. RX PubMed=17428317; DOI=10.1186/1472-6807-7-24; RA Stanley W.A., Pursiainen N.V., Garman E.F., Juffer A.H., Wilmanns M., RA Kursula P.; RT "A previously unobserved conformation for the human Pex5p receptor suggests RT roles for intrinsic flexibility and rigid domain motions in ligand RT binding."; RL BMC Struct. Biol. 7:24-24(2007). RN [34] RP STRUCTURE BY NMR OF 108-127 IN COMPLEX WITH PEX14. RX PubMed=19197237; DOI=10.1038/emboj.2009.7; RA Neufeld C., Filipp F.V., Simon B., Neuhaus A., Schueller N., David C., RA Kooshapur H., Madl T., Erdmann R., Schliebs W., Wilmanns M., Sattler M.; RT "Structural basis for competitive interactions of Pex14 with the import RT receptors Pex5 and Pex19."; RL EMBO J. 28:745-754(2009). RN [35] {ECO:0007744|PDB:4BXU} RP STRUCTURE BY NMR OF 57-71 IN COMPLEX WITH PEX14, INTERACTION WITH PEX14, RP AND MUTAGENESIS OF 62-LEU--PHE-66; TRP-118 AND TRP-140. RX PubMed=24235149; DOI=10.1074/jbc.m113.499707; RA Neuhaus A., Kooshapur H., Wolf J., Meyer N.H., Madl T., Saidowsky J., RA Hambruch E., Lazam A., Jung M., Sattler M., Schliebs W., Erdmann R.; RT "A novel Pex14 protein-interacting site of human Pex5 is critical for RT matrix protein import into peroxisomes."; RL J. Biol. Chem. 289:437-448(2014). RN [36] RP VARIANTS PBD2B LYS-526 AND TRP-600, AND CHARACTERIZATION OF VARIANTS PBD2B RP LYS-526 AND TRP-600. RX PubMed=10462504; DOI=10.1006/bbrc.1999.1232; RA Shimozawa N., Zhang Z., Suzuki Y., Imamura A., Tsukamoto T., Osumi T., RA Fujiki Y., Orii T., Barth P.G., Wanders R.J., Kondo N.; RT "Functional heterogeneity of C-terminal peroxisome targeting signal 1 in RT PEX5-defective patients."; RL Biochem. Biophys. Res. Commun. 262:504-508(1999). CC -!- FUNCTION: Receptor that mediates peroxisomal import of proteins CC containing a C-terminal PTS1-type tripeptide peroxisomal targeting CC signal (SKL-type) (PubMed:7706321, PubMed:7719337, PubMed:7790377, CC PubMed:11336669, PubMed:12456682, PubMed:16314507, PubMed:21976670, CC PubMed:26344566, PubMed:11101887, PubMed:17157249, PubMed:17428317). CC Binds to cargo proteins containing a PTS1 peroxisomal targeting signal CC in the cytosol, and translocates them into the peroxisome matrix by CC passing through the PEX13-PEX14 docking complex along with cargo CC proteins (PubMed:12456682, PubMed:21976670, PubMed:26344566, CC PubMed:17157249). PEX5 receptor is then retrotranslocated into the CC cytosol, leading to release of bound cargo in the peroxisome matrix, CC and reset for a subsequent peroxisome import cycle (PubMed:11336669, CC PubMed:24662292). {ECO:0000269|PubMed:11101887, CC ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:12456682, CC ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:17157249, CC ECO:0000269|PubMed:17428317, ECO:0000269|PubMed:21976670, CC ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, CC ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, CC ECO:0000269|PubMed:7790377}. CC -!- FUNCTION: [Isoform 1]: In addition to promoting peroxisomal CC translocation of proteins containing a PTS1 peroxisomal targeting CC signal, mediates peroxisomal import of proteins containing a C-terminal CC PTS2-type peroxisomal targeting signal via its interaction with PEX7 CC (PubMed:9668159, PubMed:11336669, PubMed:11546814, PubMed:25538232, CC PubMed:33389129). Interaction with PEX7 only takes place when PEX7 is CC associated with cargo proteins containing a PTS2 peroxisomal targeting CC signal (PubMed:25538232). PEX7 along with PTS2-containing cargo CC proteins are then translocated through the PEX13-PEX14 docking complex CC together with PEX5 (PubMed:25538232). {ECO:0000269|PubMed:11336669, CC ECO:0000269|PubMed:11546814, ECO:0000269|PubMed:25538232, CC ECO:0000269|PubMed:33389129, ECO:0000269|PubMed:9668159}. CC -!- FUNCTION: [Isoform 2]: Does not mediate translocation of peroxisomal CC import of proteins containing a C-terminal PTS2-type peroxisomal CC targeting signal. {ECO:0000269|PubMed:11546814}. CC -!- ACTIVITY REGULATION: Cys-11 acts as a sensor of redox state CC (PubMed:24118911). In response to oxidative stress, monoubiquitination CC at Cys-11 is prevented (PubMed:24118911). CC {ECO:0000269|PubMed:24118911}. CC -!- SUBUNIT: Interacts (via WxxxF/Y and LVxEF motifs) with PEX14; promoting CC translocation through the PEX13-PEX14 docking complex (PubMed:11438541, CC PubMed:24662292, PubMed:28765278, PubMed:19197237, PubMed:24235149). CC Interacts with PEX12 (PubMed:10562279). Interacts (Cys-linked CC ubiquitinated) with ZFAND6 (PubMed:21980954). Interacts (when CC ubiquitinated at Lys-209) with p62/SQSTM1 (PubMed:26344566). CC {ECO:0000269|PubMed:10562279, ECO:0000269|PubMed:11438541, CC ECO:0000269|PubMed:19197237, ECO:0000269|PubMed:21980954, CC ECO:0000269|PubMed:24235149, ECO:0000269|PubMed:24662292, CC ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:28765278}. CC -!- SUBUNIT: [Isoform 1]: Interacts with PEX7, promoting peroxisomal import CC of proteins containing a C-terminal PTS2-type peroxisomal targeting CC signal. {ECO:0000269|PubMed:11546814, ECO:0000269|PubMed:25538232, CC ECO:0000269|PubMed:33389129}. CC -!- INTERACTION: CC P50542; O14734: ACOT8; NbExp=3; IntAct=EBI-597835, EBI-1237371; CC P50542; P63010: AP2B1; NbExp=2; IntAct=EBI-597835, EBI-432924; CC P50542; Q6IMN6: CAPRIN2; NbExp=3; IntAct=EBI-597835, EBI-6918449; CC P50542; Q49A88: CCDC14; NbExp=3; IntAct=EBI-597835, EBI-751035; CC P50542; Q8WTR4: GDPD5; NbExp=3; IntAct=EBI-597835, EBI-2833203; CC P50542; P07195: LDHB; NbExp=3; IntAct=EBI-597835, EBI-358748; CC P50542; Q6NSB6: MKRN3; NbExp=3; IntAct=EBI-597835, EBI-10195599; CC P50542; O00623: PEX12; NbExp=4; IntAct=EBI-597835, EBI-594836; CC P50542; O75381: PEX14; NbExp=13; IntAct=EBI-597835, EBI-594898; CC P50542; Q9NZ81: PRR13; NbExp=3; IntAct=EBI-597835, EBI-740924; CC P50542; Q6IPH7: RPL14; NbExp=3; IntAct=EBI-597835, EBI-7813901; CC P50542; P06703: S100A6; NbExp=3; IntAct=EBI-597835, EBI-352877; CC P50542; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-597835, EBI-717399; CC P50542; Q8N5N8: TM6SF1; NbExp=3; IntAct=EBI-597835, EBI-10266890; CC P50542; Q75MR5: TOM7; NbExp=3; IntAct=EBI-597835, EBI-10255903; CC P50542; Q68DY9: ZNF772; NbExp=3; IntAct=EBI-597835, EBI-10249148; CC P50542; A8K3Q9; NbExp=3; IntAct=EBI-597835, EBI-10174314; CC P50542-1; P21549: AGXT; NbExp=4; IntAct=EBI-15982193, EBI-727098; CC P50542-3; A0A0S2Z6F4: ANKRD50; NbExp=3; IntAct=EBI-12181987, EBI-16433393; CC P50542-3; Q92990: GLMN; NbExp=3; IntAct=EBI-12181987, EBI-726150; CC P50542-3; P31943: HNRNPH1; NbExp=3; IntAct=EBI-12181987, EBI-351590; CC P50542-3; P07602: PSAP; NbExp=3; IntAct=EBI-12181987, EBI-716699; CC P50542-3; Q96FV2: SCRN2; NbExp=3; IntAct=EBI-12181987, EBI-11306862; CC P50542-3; Q13501: SQSTM1; NbExp=2; IntAct=EBI-12181987, EBI-307104; CC P50542-3; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-12181987, EBI-6268651; CC P50542-3; Q9H8U3: ZFAND3; NbExp=3; IntAct=EBI-12181987, EBI-725171; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11336669, CC ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:7719337}. Peroxisome CC matrix {ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:11546814, CC ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:24662292, CC ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:33389129, CC ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337}. Note=Cycles CC between the cytosol and the peroxisome matrix (PubMed:11336669, CC PubMed:16314507). Following binding to cargo proteins containing a PTS1 CC peroxisomal targeting signal in the cytosol, recruited to the docking CC complex, composed of PEX13 and PEX14, leading to translocation into the CC peroxisome matrix along with cargo proteins (By similarity). 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 (By similarity). Cys-11 of CC PEX5 is then monoubiquitinated, promoting its extraction from CC peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex CC (PubMed:16314507, PubMed:19208625, PubMed:24118911, PubMed:29884772). CC Extraction is accompanied by unfolding of the TPR repeats and release CC of bound cargo in the peroxisome matrix (By similarity). The TPR CC repeats refold in the cytosol and ubiquitination is removed by CC deubiquitinating enzymes, resetting PEX5 for a subsequent import cycle CC (By similarity). {ECO:0000250|UniProtKB:A0A1L8FDW4, CC ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:16314507, CC ECO:0000269|PubMed:19208625, ECO:0000269|PubMed:24118911, CC ECO:0000269|PubMed:29884772}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=PEX5L {ECO:0000303|PubMed:11546814}; CC IsoId=P50542-1; Sequence=Displayed; CC Name=2; Synonyms=PEX5S {ECO:0000303|PubMed:11546814}; CC IsoId=P50542-2; Sequence=VSP_021880; CC Name=3; CC IsoId=P50542-3; Sequence=VSP_024106; CC Name=4; CC IsoId=P50542-4; Sequence=VSP_043639; CC -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, lung, liver, CC skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:7706321, CC ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}. CC -!- DOMAIN: The TPR repeats mediate interaction with proteins containing a CC C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL- CC type). {ECO:0000269|PubMed:11101887, ECO:0000269|PubMed:17157249}. CC -!- DOMAIN: The WxxxF/Y motifs mediate interaction with PEX14, promoting CC association with the PEX13-PEX14 docking complex. CC {ECO:0000269|PubMed:11438541}. CC -!- DOMAIN: The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are CC required for PEX5 retrotranslocation and recycling (By similarity). AH2 CC mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase CC complex, while AH1 is required for extraction from peroxisomal membrane CC by the PEX1-PEX6 AAA ATPase complex (By similarity). CC {ECO:0000250|UniProtKB:A0A1L8FDW4}. CC -!- PTM: Monoubiquitinated at Cys-11 by PEX2 during PEX5 passage through CC the retrotranslocation channel (By similarity). Cys-11 CC monoubiquitination acts as a recognition signal for the PEX1-PEX6 CC complex and is required for PEX5 extraction and export from peroxisomes CC (PubMed:29884772). Monoubiquitination at Cys-11 is removed by USP9X in CC the cytosol, resetting PEX5 for a subsequent import cycle CC (PubMed:22371489). When PEX5 recycling is compromised, CC polyubiquitinated by PEX10 during its passage through the CC retrotranslocation channel, leading to its degradation (By similarity). CC Monoubiquitination at Lys-472 by TRIM37 promotes its stability by CC preventing its polyubiquitination and degradation by the proteasome CC (PubMed:28724525). Ubiquitination at Lys-527 is not mediated by the CC PEX2-PEX10-PEX12 ligase complex and is not related to PEX5 recycling CC (PubMed:24662292). Monoubiquitinated at Lys-209 by PEX2 following CC phosphorylation by ATM in response to starvation or reactive oxygen CC species (ROS), leading to PEX5 recognition by p62/SQSTM1 and induction CC of pexophagy (PubMed:26344566, PubMed:27597759). CC {ECO:0000250|UniProtKB:P35056, ECO:0000269|PubMed:22371489, CC ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, CC ECO:0000269|PubMed:27597759, ECO:0000269|PubMed:28724525, CC ECO:0000269|PubMed:29884772}. CC -!- PTM: Phosphorylated at Ser-141 by ATM in response to reactive oxygen CC species (ROS), promoting monoubiquitination at Lys-209 and induction of CC pexophagy. {ECO:0000269|PubMed:26344566}. CC -!- DISEASE: Peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110]: A CC fatal peroxisome biogenesis disorder belonging to the Zellweger disease CC spectrum and characterized clinically by severe neurologic dysfunction CC with profound psychomotor retardation, severe hypotonia and neonatal CC seizures, craniofacial abnormalities, liver dysfunction, and CC biochemically by the absence of peroxisomes. Additional features CC include cardiovascular and skeletal defects, renal cysts, ocular CC abnormalities, and hearing impairment. Most severely affected CC individuals with the classic form of the disease (classic Zellweger CC syndrome) die within the first year of life. CC {ECO:0000269|PubMed:7719337}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370]: A CC peroxisome biogenesis disorder that includes neonatal CC adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two CC milder manifestations of the Zellweger disease spectrum. The clinical CC course of patients with the NALD and IRD presentation is variable and CC may include developmental delay, hypotonia, liver dysfunction, CC sensorineural hearing loss, retinal dystrophy and vision impairment. CC Children with the NALD presentation may reach their teens, while CC patients with the IRD presentation may reach adulthood. The clinical CC conditions are often slowly progressive in particular with respect to CC loss of hearing and vision. The biochemical abnormalities include CC accumulation of phytanic acid, very long chain fatty acids (VLCFA), CC di- and trihydroxycholestanoic acid and pipecolic acid. CC {ECO:0000269|PubMed:10462504, ECO:0000269|PubMed:7719337, CC ECO:0000269|PubMed:9668159}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Rhizomelic chondrodysplasia punctata 5 (RCDP5) [MIM:616716]: A CC form of rhizomelic chondrodysplasia punctata, a disease characterized CC by severely disturbed endochondral bone formation, rhizomelic CC shortening of femur and humerus, vertebral disorders, dwarfism, CC cataract, cutaneous lesions, facial dysmorphism, and severe CC intellectual disability with spasticity. {ECO:0000269|PubMed:26220973}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the peroxisomal targeting signal receptor CC 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; U19721; AAC50103.1; -; mRNA. DR EMBL; Z48054; CAA88131.1; -; mRNA. DR EMBL; X84899; CAA59324.1; -; mRNA. DR EMBL; AK292256; BAF84945.1; -; mRNA. DR EMBL; AK302742; BAG63957.1; -; mRNA. DR EMBL; AK316250; BAH14621.1; -; mRNA. DR EMBL; AC018653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471116; EAW88671.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88674.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88672.1; -; Genomic_DNA. DR EMBL; BC010621; AAH10621.1; -; mRNA. DR CCDS; CCDS44822.1; -. [P50542-4] DR CCDS; CCDS44823.1; -. [P50542-1] DR CCDS; CCDS44824.1; -. [P50542-2] DR CCDS; CCDS8576.1; -. [P50542-3] DR PIR; A56126; A56126. DR RefSeq; NP_000310.2; NM_000319.4. [P50542-3] DR RefSeq; NP_001124495.1; NM_001131023.1. [P50542-4] DR RefSeq; NP_001124496.1; NM_001131024.1. [P50542-2] DR RefSeq; NP_001124497.1; NM_001131025.1. [P50542-1] DR RefSeq; NP_001124498.1; NM_001131026.1. [P50542-1] DR RefSeq; NP_001287718.1; NM_001300789.1. [P50542-1] DR RefSeq; XP_011519097.1; XM_011520795.1. [P50542-4] DR RefSeq; XP_011519099.1; XM_011520797.1. DR RefSeq; XP_011519100.1; XM_011520798.1. DR RefSeq; XP_011519101.1; XM_011520799.2. DR RefSeq; XP_011519102.1; XM_011520800.1. DR RefSeq; XP_016875237.1; XM_017019748.1. [P50542-4] DR RefSeq; XP_016875238.1; XM_017019749.1. DR RefSeq; XP_016875239.1; XM_017019750.1. DR RefSeq; XP_016875241.1; XM_017019752.1. DR RefSeq; XP_016875242.1; XM_017019753.1. DR RefSeq; XP_016875243.1; XM_017019754.1. DR RefSeq; XP_016875244.1; XM_017019755.1. DR PDB; 1FCH; X-ray; 2.20 A; A/B=272-639. DR PDB; 2C0L; X-ray; 2.30 A; A=335-639. DR PDB; 2C0M; X-ray; 2.50 A; A/B/C/F=321-639. DR PDB; 2J9Q; X-ray; 2.65 A; A/B=315-639. DR PDB; 2W84; NMR; -; B=108-127. DR PDB; 3R9A; X-ray; 2.35 A; B/D=315-639. DR PDB; 4BXU; NMR; -; B=57-71. DR PDB; 4KXK; X-ray; 2.90 A; B/D=315-639. DR PDB; 4KYO; X-ray; 2.20 A; B/D=315-639. DR PDB; 7Z0K; X-ray; 2.30 A; A/B=179-192. DR PDBsum; 1FCH; -. DR PDBsum; 2C0L; -. DR PDBsum; 2C0M; -. DR PDBsum; 2J9Q; -. DR PDBsum; 2W84; -. DR PDBsum; 3R9A; -. DR PDBsum; 4BXU; -. DR PDBsum; 4KXK; -. DR PDBsum; 4KYO; -. DR PDBsum; 7Z0K; -. DR AlphaFoldDB; P50542; -. DR SMR; P50542; -. DR BioGRID; 111788; 222. DR DIP; DIP-34654N; -. DR ELM; P50542; -. DR IntAct; P50542; 65. DR MINT; P50542; -. DR STRING; 9606.ENSP00000391601; -. DR iPTMnet; P50542; -. DR MetOSite; P50542; -. DR PhosphoSitePlus; P50542; -. DR SwissPalm; P50542; -. DR BioMuta; PEX5; -. DR DMDM; 119364633; -. DR EPD; P50542; -. DR jPOST; P50542; -. DR MassIVE; P50542; -. DR MaxQB; P50542; -. DR PaxDb; P50542; -. DR PeptideAtlas; P50542; -. DR ProteomicsDB; 56239; -. [P50542-1] DR ProteomicsDB; 56240; -. [P50542-2] DR ProteomicsDB; 56241; -. [P50542-3] DR ProteomicsDB; 56242; -. [P50542-4] DR Antibodypedia; 22900; 320 antibodies from 32 providers. DR DNASU; 5830; -. DR Ensembl; ENST00000266563.9; ENSP00000266563.5; ENSG00000139197.11. [P50542-2] DR Ensembl; ENST00000266564.7; ENSP00000266564.3; ENSG00000139197.11. [P50542-3] DR Ensembl; ENST00000420616.6; ENSP00000410159.2; ENSG00000139197.11. [P50542-1] DR Ensembl; ENST00000434354.6; ENSP00000407401.2; ENSG00000139197.11. [P50542-4] DR Ensembl; ENST00000455147.6; ENSP00000400647.2; ENSG00000139197.11. [P50542-1] DR Ensembl; ENST00000671993.1; ENSP00000500509.1; ENSG00000288217.3. [P50542-1] DR Ensembl; ENST00000672242.1; ENSP00000500696.1; ENSG00000288217.3. [P50542-2] DR Ensembl; ENST00000672541.1; ENSP00000500043.1; ENSG00000288217.3. [P50542-4] DR Ensembl; ENST00000672694.1; ENSP00000499823.1; ENSG00000288217.3. [P50542-1] DR Ensembl; ENST00000672776.1; ENSP00000500230.1; ENSG00000288217.3. [P50542-3] DR Ensembl; ENST00000675855.1; ENSP00000502374.1; ENSG00000139197.11. [P50542-1] DR GeneID; 5830; -. DR KEGG; hsa:5830; -. DR MANE-Select; ENST00000675855.1; ENSP00000502374.1; NM_001351132.2; NP_001338061.1. DR UCSC; uc001qsu.4; human. [P50542-1] DR AGR; HGNC:9719; -. DR CTD; 5830; -. DR DisGeNET; 5830; -. DR GeneCards; PEX5; -. DR GeneReviews; PEX5; -. DR HGNC; HGNC:9719; PEX5. DR HPA; ENSG00000139197; Low tissue specificity. DR MalaCards; PEX5; -. DR MIM; 202370; phenotype. DR MIM; 214110; phenotype. DR MIM; 600414; gene. DR MIM; 616716; phenotype. DR neXtProt; NX_P50542; -. DR OpenTargets; ENSG00000139197; -. DR Orphanet; 772; Infantile Refsum disease. DR Orphanet; 44; Neonatal adrenoleukodystrophy. DR Orphanet; 468717; Rhizomelic chondrodysplasia punctata type 5. DR Orphanet; 912; Zellweger syndrome. DR PharmGKB; PA34063; -. DR VEuPathDB; HostDB:ENSG00000139197; -. DR eggNOG; KOG1125; Eukaryota. DR GeneTree; ENSGT00940000156605; -. DR HOGENOM; CLU_013516_4_0_1; -. DR InParanoid; P50542; -. DR OMA; NYRMKGP; -. DR OrthoDB; 2020042at2759; -. DR PhylomeDB; P50542; -. DR TreeFam; TF315044; -. DR PathwayCommons; P50542; -. DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR Reactome; R-HSA-9664873; Pexophagy. DR SignaLink; P50542; -. DR SIGNOR; P50542; -. DR BioGRID-ORCS; 5830; 65 hits in 1164 CRISPR screens. DR ChiTaRS; PEX5; human. DR EvolutionaryTrace; P50542; -. DR GeneWiki; PEX5; -. DR GenomeRNAi; 5830; -. DR Pharos; P50542; Tbio. DR PRO; PR:P50542; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P50542; protein. DR Bgee; ENSG00000139197; Expressed in gastrocnemius and 100 other tissues. DR ExpressionAtlas; P50542; baseline and differential. DR Genevisible; P50542; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB. DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005052; F:peroxisome matrix targeting signal-1 binding; IDA:UniProtKB. DR GO; GO:0033328; F:peroxisome membrane targeting sequence binding; IPI:UniProtKB. DR GO; GO:0000268; F:peroxisome targeting sequence binding; IDA:UniProtKB. DR GO; GO:0140597; F:protein carrier chaperone; IDA:UniProtKB. DR GO; GO:0044183; F:protein folding chaperone; IDA:DisProt. DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB. DR GO; GO:0048468; P:cell development; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:UniProt. DR GO; GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl. DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IEA:Ensembl. DR GO; GO:0007029; P:endoplasmic reticulum organization; IEA:Ensembl. DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:Ensembl. DR GO; GO:0007006; P:mitochondrial membrane organization; IEA:Ensembl. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0000425; P:pexophagy; IDA:UniProtKB. DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0016558; P:protein import into peroxisome matrix; IDA:UniProtKB. DR GO; GO:0016560; P:protein import into peroxisome matrix, docking; IDA:UniProtKB. DR GO; GO:0016562; P:protein import into peroxisome matrix, receptor recycling; IDA:UniProtKB. DR GO; GO:0044721; P:protein import into peroxisome matrix, substrate release; IDA:UniProt. DR GO; GO:0016561; P:protein import into peroxisome matrix, translocation; IDA:UniProtKB. DR GO; GO:0045046; P:protein import into peroxisome membrane; IMP:UniProtKB. DR GO; GO:0006625; P:protein targeting to peroxisome; IDA:UniProtKB. DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB. DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IEA:Ensembl. DR DisProt; DP00472; -. 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; IPR019734; TPR_repeat. DR PANTHER; PTHR10130:SF2; PEROXISOMAL TARGETING SIGNAL 1 RECEPTOR; 1. DR PANTHER; PTHR10130; PEROXISOMAL TARGETING SIGNAL 1 RECEPTOR PEX5; 1. DR Pfam; PF13432; TPR_16; 2. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00028; TPR; 4. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 5. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Isopeptide bond; Peroxisome; Peroxisome biogenesis disorder; KW Phosphoprotein; Protein transport; Reference proteome; Repeat; KW Rhizomelic chondrodysplasia punctata; Thioester bond; TPR repeat; KW Translocation; Transport; Ubl conjugation; Zellweger syndrome. FT CHAIN 1..639 FT /note="Peroxisomal targeting signal 1 receptor" FT /id="PRO_0000106305" FT REPEAT 335..368 FT /note="TPR 1" FT REPEAT 369..402 FT /note="TPR 2" FT REPEAT 403..436 FT /note="TPR 3" FT REPEAT 452..485 FT /note="TPR 4" FT REPEAT 488..521 FT /note="TPR 5" FT REPEAT 522..555 FT /note="TPR 6" FT REPEAT 556..589 FT /note="TPR 7" FT REGION 11..33 FT /note="Amphipathic helix 1 (AH1)" FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4" FT REGION 33..53 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 81..99 FT /note="Amphipathic helix 2 (AH2)" FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4" FT REGION 190..206 FT /note="Amphipathic helix 3 (AH3)" FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4" FT REGION 284..300 FT /note="Amphipathic helix 4 (AH4)" FT /evidence="ECO:0000250|UniProtKB:A0A1L8FDW4" FT MOTIF 62..66 FT /note="LVxEF motif" FT /evidence="ECO:0000269|PubMed:24235149" FT MOTIF 118..122 FT /note="WxxxF/Y motif 1" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 140..144 FT /note="WxxxF/Y motif 2" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 159..163 FT /note="WxxxF/Y motif 3" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 184..188 FT /note="WxxxF/Y motif 4" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 243..247 FT /note="WxxxF/Y motif 5" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 257..261 FT /note="WxxxF/Y motif 6" FT /evidence="ECO:0000269|PubMed:11438541" FT MOTIF 308..312 FT /note="WxxxF/Y motif 7" FT /evidence="ECO:0000269|PubMed:11438541" FT SITE 11 FT /note="Sensor of redox state" FT /evidence="ECO:0000269|PubMed:24118911" FT MOD_RES 115 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 141 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:26344566" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 155 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 167 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 279 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 11 FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:19208625, FT ECO:0000269|PubMed:22371489, ECO:0000269|PubMed:24118911, FT ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:29884772" FT CROSSLNK 209 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:26344566" FT CROSSLNK 472 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:28724525" FT CROSSLNK 527 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:24662292" FT VAR_SEQ 45 FT /note="P -> PASEAVSVLEVESPGA (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043639" FT VAR_SEQ 215..251 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:7719337, ECO:0000303|PubMed:7790377" FT /id="VSP_021880" FT VAR_SEQ 283..290 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024106" FT VARIANT 218 FT /note="F -> S (probable disease-associated variant found in FT a family with congenital cataract; impaired interaction FT with PEX7; impaired ability to mediate peroxisomal import FT of proteins containing a C-terminal PTS2-type targeting FT signal without affecting import of proteins with a PTS1 FT targeting signal)" FT /evidence="ECO:0000269|PubMed:33389129" FT /id="VAR_087152" FT VARIANT 427..639 FT /note="Missing (in PBD2B; impaired ability to mediate FT peroxisomal import of proteins containing both a C-terminal FT PTS1- and PTS2-type targeting signals)" FT /evidence="ECO:0000269|PubMed:7719337, FT ECO:0000269|PubMed:9668159" FT /id="VAR_087153" FT VARIANT 526 FT /note="N -> K (in PBD2B; neonatal adrenoleukodystrophy; FT strongly affects peroxisomal protein import containing a C- FT terminal PTS1-type targeting signal without affecting FT import of proteins with a PTS2 targeting signal; FT dbSNP:rs61752138)" FT /evidence="ECO:0000269|PubMed:10462504, FT ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:9668159" FT /id="VAR_007543" FT VARIANT 600 FT /note="S -> W (in PBD2B; infantile Refsum disease; mildly FT affects peroxisomal protein import)" FT /evidence="ECO:0000269|PubMed:10462504" FT /id="VAR_031328" FT MUTAGEN 11 FT /note="C->A: Promotes accumulation at the peroxisomal FT membrane because of impaired export into the cytosol. Does FT not affect monoubiquitination by TRIM37." FT /evidence="ECO:0000269|PubMed:19208625, FT ECO:0000269|PubMed:28724525, ECO:0000269|PubMed:28765278" FT MUTAGEN 11 FT /note="C->K: Does not affect ability to mediate peroxisomal FT import of proteins." FT /evidence="ECO:0000269|PubMed:19208625, FT ECO:0000269|PubMed:22371489, ECO:0000269|PubMed:24118911" FT MUTAGEN 11 FT /note="C->S,R: Promotes accumulation at the peroxisomal FT membrane because of impaired export into the cytosol." FT /evidence="ECO:0000269|PubMed:19208625" FT MUTAGEN 62..66 FT /note="LVAEF->AAAAA: Abolished interaction with PEX14." FT /evidence="ECO:0000269|PubMed:24235149" FT MUTAGEN 118 FT /note="W->A: Strongly reduced interaction with PEX14." FT /evidence="ECO:0000269|PubMed:11438541, FT ECO:0000269|PubMed:24235149" FT MUTAGEN 122 FT /note="F->A: Strongly reduced interaction with PEX14." FT /evidence="ECO:0000269|PubMed:11438541" FT MUTAGEN 140 FT /note="W->A: Decreased interaction with PEX14." FT /evidence="ECO:0000269|PubMed:24235149" FT MUTAGEN 141 FT /note="S->A: Abolished phosphorylation by ATM, leading to FT impaired monoubiquitination at K-209." FT /evidence="ECO:0000269|PubMed:26344566" FT MUTAGEN 141 FT /note="S->E: Mimics phosphorylation, leading to increased FT pexophagy in response to reactive oxygen species (ROS)." FT /evidence="ECO:0000269|PubMed:26344566" FT MUTAGEN 209 FT /note="K->A: Does not affect monoubiquitination by TRIM37." FT /evidence="ECO:0000269|PubMed:28724525" FT MUTAGEN 209 FT /note="K->R: Abolished interaction with SQSTM1, leading to FT decreased pexophagy in response to reactive oxygen species FT (ROS)." FT /evidence="ECO:0000269|PubMed:26344566" FT MUTAGEN 472 FT /note="K->A: Abolished monoubiquitination by TRIM37, FT leading to decreased stability." FT /evidence="ECO:0000269|PubMed:28724525" FT MUTAGEN 527 FT /note="K->A: Does not affect monoubiquitination by TRIM37." FT /evidence="ECO:0000269|PubMed:28724525" FT MUTAGEN 527 FT /note="K->R: Does not affect PEX5 recycling." FT /evidence="ECO:0000269|PubMed:24662292" FT CONFLICT 425 FT /note="T -> I (in Ref. 1; AAC50103)" FT /evidence="ECO:0000305" FT HELIX 60..69 FT /evidence="ECO:0007829|PDB:4BXU" FT HELIX 109..124 FT /evidence="ECO:0007829|PDB:2W84" FT HELIX 318..321 FT /evidence="ECO:0007829|PDB:1FCH" FT TURN 331..334 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 338..347 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 351..363 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 369..381 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 385..398 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 403..415 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 419..431 FT /evidence="ECO:0007829|PDB:1FCH" FT TURN 434..436 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 437..439 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 460..481 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 488..500 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 504..517 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 522..534 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 538..551 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 556..569 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 572..587 FT /evidence="ECO:0007829|PDB:1FCH" FT STRAND 593..595 FT /evidence="ECO:0007829|PDB:2C0L" FT HELIX 601..614 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 617..619 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 620..624 FT /evidence="ECO:0007829|PDB:1FCH" FT HELIX 628..634 FT /evidence="ECO:0007829|PDB:1FCH" SQ SEQUENCE 639 AA; 70865 MW; 9D6951F58AED31AC CRC64; MAMRELVEAE CGGANPLMKL AGHFTQDKAL RQEGLRPGPW PPGAPASEAA SKPLGVASED ELVAEFLQDQ NAPLVSRAPQ TFKMDDLLAE MQQIEQSNFR QAPQRAPGVA DLALSENWAQ EFLAAGDAVD VTQDYNETDW SQEFISEVTD PLSVSPARWA EEYLEQSEEK LWLGEPEGTA TDRWYDEYHP EEDLQHTASD FVAKVDDPKL ANSEFLKFVR QIGEGQVSLE SGAGSGRAQA EQWAAEFIQQ QGTSDAWVDQ FTRPVNTSAL DMEFERAKSA IESDVDFWDK LQAELEEMAK RDAEAHPWLS DYDDLTSATY DKGYQFEEEN PLRDHPQPFE EGLRRLQEGD LPNAVLLFEA AVQQDPKHME AWQYLGTTQA ENEQELLAIS ALRRCLELKP DNQTALMALA VSFTNESLQR QACETLRDWL RYTPAYAHLV TPAEEGAGGA GLGPSKRILG SLLSDSLFLE VKELFLAAVR LDPTSIDPDV QCGLGVLFNL SGEYDKAVDC FTAALSVRPN DYLLWNKLGA TLANGNQSEE AVAAYRRALE LQPGYIRSRY NLGISCINLG AHREAVEHFL EALNMQRKSR GPRGEGGAMS ENIWSTLRLA LSMLGQSDAY GAADARDLST LLTMFGLPQ //