ID PEX5_HUMAN Reviewed; 639 AA. AC P50542; Q15115; Q15266; Q96FN7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 3. DT 02-OCT-2007, entry version 78. DE Peroxisomal targeting signal 1 receptor (Peroxisome receptor 1) DE (Peroxisomal C-terminal targeting signal import receptor) (PTS1-BP) DE (Peroxin-5) (PTS1 receptor). GN Name=PEX5; Synonyms=PXR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INVOLVEMENT IN ZWS, VARIANT RP NALD LYS-526, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX MEDLINE=95235555; PubMed=7719337; DOI=10.1038/ng0295-115; RA Dodt G., Braverman N., Wong C., Moser A., Moser H.W., Watkins P., RA Valle D., Gould S.J.; RT "Mutations in the PTS1 receptor gene, PXR1, define complementation RT group 2 of the peroxisome biogenesis disorders."; RL Nat. Genet. 9:115-125(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Liver; RX MEDLINE=95310365; 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 RT protein import in cells from patients with fatal peroxisomal RT disorders."; RL J. Cell Biol. 130:51-65(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, RP AND SUBCELLULAR LOCATION. RC TISSUE=Liver; RX MEDLINE=95221441; 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 RT C-terminal targeting signal import receptor."; RL J. Biol. Chem. 270:7731-7736(1995). RN [4] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] 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 [6] 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 RT peroxisomal membrane protein PEX14."; RL J. Biol. Chem. 276:34524-34529(2001). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 272-639 IN COMPLEX WITH RP TARGETING 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 RT human PEX5."; RL Nat. Struct. Biol. 7:1091-1095(2000). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 321-639 IN COMPLEX WITH RP TARGETING PEPTIDE. RX PubMed=17157249; DOI=10.1016/j.molcel.2006.10.024; RA Stanley W.A., Filipp F.V., Kursula P., Schuller N., Erdmann R., RA Schliebs W., Sattler M., Wilmanns M.; RT "Recognition of a functional peroxisome type 1 target by the dynamic RT import receptor pex5p."; RL Mol. Cell 24:653-663(2006). RN [9] RP VARIANT NALD LYS-526, VARIANT IRD TRP-600, CHARACTERIZATION OF VARIANT RP NALD LYS-526, AND CHARACTERIZATION OF VARIANT IRD 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 RT in 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 CC peroxisomal protein import. CC -!- SUBUNIT: Interacts with PEX7 and PEX13 (By similarity). Interacts CC with PEX12 and PEX14. CC -!- INTERACTION: CC O00623:PEX12; NbExp=2; IntAct=EBI-597835, EBI-594836; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Peroxisome membrane; Peripheral CC membrane protein. Note=Its distribution appears to be dynamic. It CC is probably a cycling receptor found mainly in the cytoplasm and CC as well associated to the peroxisomal membrane through a docking CC factor (PEX13). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; 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 -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, lung, CC liver, skeletal muscle, kidney and pancreas. CC -!- DISEASE: Defects in PEX5 are a cause of neonatal CC adrenoleukodystrophy (NALD) [MIM:202370]. NALD is a peroxisome CC biogenesis disorder (PBD) characterized by the accumulation of CC very long-chain fatty acids, adrenal insufficiency and mental CC retardation. Inheritance is autosomal recessive. CC -!- DISEASE: Defects in PEX5 are a cause of Zellweger syndrome (ZWS) CC [MIM:214100]. ZWS is a fatal peroxisome biogenesis disorder CC characterized by dysmorphic facial features, hepatomegaly, ocular CC abnormalities, renal cysts, hearing impairment, profound CC psychomotor retardation, severe hypotonia and neonatal seizures. CC Death occurs within the first year of life. CC -!- DISEASE: Defects in PEX5 may be a cause of infantile Refsum CC disease (IRD) [MIM:266510]. IRD is a mild peroxisome biogenesis CC disorder (PBD). Clinical features include early onset, mental CC retardation, minor facial dysmorphism, retinopathy, sensorineural CC hearing deficit, hepatomegaly, osteoporosis, failure to thrive, CC and hypocholesterolemia. The biochemical abnormalities include CC accumulation of phytanic acid, very long chain fatty acids CC (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. CC -!- SIMILARITY: Belongs to the peroxisomal targeting signal receptor CC family. CC -!- SIMILARITY: Contains 7 TPR repeats. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=PEX5"; 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; BC010621; AAH10621.1; -; mRNA. DR PIR; A56126; A56126. DR RefSeq; NP_000310.2; -. DR UniGene; Hs.567327; -. DR PDB; 1FCH; X-ray; A/B=272-639. DR PDB; 2C0L; X-ray; A=335-639. DR PDB; 2C0M; X-ray; A/B/C/F=321-639. DR IntAct; P50542; -. DR Ensembl; ENSG00000139197; Homo sapiens. DR GeneID; 5830; -. DR KEGG; hsa:5830; -. DR HGNC; HGNC:9719; PEX5. DR MIM; 202370; phenotype. DR MIM; 214100; phenotype. DR MIM; 266510; phenotype. DR MIM; 600414; gene. DR Orphanet; 44; Adrenoleukodystrophy, neonatal. DR Orphanet; 772; Refsum disease, infantile form. DR Orphanet; 912; Zellweger syndrome. DR PharmGKB; PA34063; -. DR LinkHub; P50542; -. DR ArrayExpress; P50542; -. DR GermOnline; ENSG00000139197; Homo sapiens. DR GO; GO:0005778; C:peroxisomal membrane; TAS:ProtInc. DR GO; GO:0005052; F:peroxisome matrix targeting signal-1 binding; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR013026; TPR_region. DR Pfam; PF00515; TPR_1; 4. DR SMART; SM00028; TPR; 4. DR PROSITE; PS50005; TPR; 5. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease mutation; KW Membrane; Peroxisome; Peroxisome biogenesis disorder; KW Protein transport; Repeat; TPR repeat; Transport; Zellweger syndrome. FT CHAIN 1 639 Peroxisomal targeting signal 1 receptor. FT /FTId=PRO_0000106305. FT REPEAT 335 368 TPR 1. FT REPEAT 369 402 TPR 2. FT REPEAT 403 436 TPR 3. FT REPEAT 452 485 TPR 4. FT REPEAT 488 521 TPR 5. FT REPEAT 522 555 TPR 6. FT REPEAT 556 589 TPR 7. FT VAR_SEQ 215 251 Missing (in isoform 2). FT /FTId=VSP_021880. FT VAR_SEQ 283 290 Missing (in isoform 3). FT /FTId=VSP_024106. FT VARIANT 526 526 N -> K (in NALD; strongly affects FT peroxisomal protein import). FT /FTId=VAR_007543. FT VARIANT 600 600 S -> W (in IRD; mildly affects FT peroxisomal protein import). FT /FTId=VAR_031328. FT MUTAGEN 118 118 W->A: Strongly reduced interaction with FT PEX14. FT MUTAGEN 122 122 F->A: Strongly reduced interaction with FT PEX14. FT CONFLICT 425 425 T -> I (in Ref. 1; AAC50103). FT HELIX 281 284 FT TURN 294 297 FT HELIX 301 310 FT HELIX 314 326 FT HELIX 332 344 FT HELIX 348 361 FT HELIX 366 378 FT HELIX 382 394 FT TURN 397 399 FT HELIX 400 402 FT HELIX 423 444 FT HELIX 451 463 FT HELIX 467 480 FT HELIX 485 497 FT HELIX 501 514 FT HELIX 519 532 FT HELIX 535 550 FT HELIX 564 577 FT HELIX 580 582 FT HELIX 583 587 FT HELIX 591 597 FT HELIX 617 624 FT HELIX 628 634 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 //