PEX5_HUMAN
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 03-AUG-2022, entry version 217.
DE RecName: Full=Peroxisomal targeting signal 1 receptor;
DE Short=PTS1 receptor;
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; Synonyms=PXR1;
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, VARIANT PBD2B
RP LYS-526, FUNCTION, SUBCELLULAR LOCATION, AND 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 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 [9]
RP INTERACTION WITH PEX14, AND MUTAGENESIS OF TRP-118 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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 272-639 IN COMPLEX WITH TARGETING
RP PEPTIDE.
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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 321-639 IN COMPLEX WITH TARGETING
RP PEPTIDE.
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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 315-639, AND BINDING TO
RP C-TERMINAL TARGETING PEPTIDES.
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 [17]
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 [18]
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: Binds to the C-terminal PTS1-type tripeptide peroxisomal
CC targeting signal (SKL-type) and plays an essential role in peroxisomal
CC protein import. {ECO:0000269|PubMed:7706321,
CC ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.
CC -!- SUBUNIT: Interacts with PEX7 and PEX13 (By similarity). Interacts with
CC PEX12 and PEX14. Interacts (Cys-linked ubiquitinated) with ZFAND6.
CC Interacts with VWA8 in a PEX7-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:Q920N5, ECO:0000269|PubMed:10562279,
CC ECO:0000269|PubMed:11101887, ECO:0000269|PubMed:11438541,
CC ECO:0000269|PubMed:17157249, ECO:0000269|PubMed:19197237,
CC ECO:0000269|PubMed:21980954}.
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 {ECO:0000269|PubMed:7719337}.
CC Peroxisome membrane {ECO:0000269|PubMed:7706321,
CC ECO:0000269|PubMed:7719337}; Peripheral membrane protein. Note=Its
CC distribution appears to be dynamic. It is probably a cycling receptor
CC found mainly in the cytoplasm and as well associated to the peroxisomal
CC membrane through a docking factor (PEX13).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P50542-1; Sequence=Displayed;
CC Name=2;
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 -!- PTM: Monoubiquitination at Cys-11 is required for proper export from
CC peroxisomes and recycling. {ECO:0000250|UniProtKB:Q920N5}.
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}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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}.
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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; CCDS73433.1; -. [P50542-1]
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. [P50542-1]
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 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 AlphaFoldDB; P50542; -.
DR SMR; P50542; -.
DR BioGRID; 111788; 215.
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 BioMuta; PEX5; -.
DR DMDM; 119364633; -.
DR EPD; P50542; -.
DR jPOST; P50542; -.
DR MassIVE; P50542; -.
DR MaxQB; P50542; -.
DR PaxDb; P50542; -.
DR PeptideAtlas; P50542; -.
DR PRIDE; P50542; -.
DR ProteomicsDB; 56239; -. [P50542-1]
DR ProteomicsDB; 56240; -. [P50542-2]
DR ProteomicsDB; 56241; -. [P50542-3]
DR ProteomicsDB; 56242; -. [P50542-4]
DR Antibodypedia; 22900; 289 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 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; 588648at2759; -.
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; 63 hits in 1086 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:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0140311; F:protein sequestering activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0048468; P:cell development; IEA:Ensembl.
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:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0016558; P:protein import into peroxisome matrix; IMP:UniProtKB.
DR GO; GO:0016560; P:protein import into peroxisome matrix, docking; IDA:UniProtKB.
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; -; 1.
DR InterPro; IPR024111; PEX5/PEX5L.
DR InterPro; IPR024113; PEX5_animals.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10130; PTHR10130; 1.
DR PANTHER; PTHR10130:SF2; PTHR10130:SF2; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 4.
DR SUPFAM; SSF48452; SSF48452; 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; Membrane;
KW Peroxisome; Peroxisome biogenesis disorder; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat;
KW Rhizomelic chondrodysplasia punctata; Thioester bond; TPR repeat;
KW 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 33..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
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:0000250|UniProtKB:Q920N5"
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 526
FT /note="N -> K (in PBD2B; neonatal adrenoleukodystrophy;
FT strongly affects peroxisomal protein import;
FT dbSNP:rs61752138)"
FT /evidence="ECO:0000269|PubMed:10462504,
FT ECO:0000269|PubMed:7719337"
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 118
FT /note="W->A: Strongly reduced interaction with PEX14."
FT /evidence="ECO:0000269|PubMed:11438541"
FT MUTAGEN 122
FT /note="F->A: Strongly reduced interaction with PEX14."
FT /evidence="ECO:0000269|PubMed:11438541"
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
