Home LiteratureArticle Details
PMID: 8670792 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor.

The EMBO journal ·Vol. 15 ·No. 12 ·1996-06-17 ·Pages 2914-23

Yahraus T, Braverman N, Dodt G, Kalish JE, Morrell JC, Moser HW, Valle D, Gould SJ

Abstract

In humans, defects in peroxisome assembly result in the peroxisome biogenesis disorders (PBDs), a group of genetically heterogeneous, lethal recessive diseases. We have identified the human gene PXAAA1 based upon its similarity to PpPAS5, a gene required for peroxisome assembly in the yeast Pichia pastoris. Expression of PXAAA1 restored peroxisomal protein import in fibroblasts from 16 unrelated members of complementation group 4 (CG4) of the PBD. Consistent with this observation, CG4 patients carry mutations in PXAAA1. The product of this gene, Pxaaa1p, belongs to the AAA family of ATPases and appears to be a predominantly cytoplasmic protein. Substitution of an arginine for the conserved lysine residue in the ATPase domain of Pxaaa1p abolished its biological activity, suggesting that Pxaaa1p is an ATPase. Furthermore, Pxaaa1p is required for stability of the predominantly cytoplasmic PTS1 receptor, Pxr1p. We conclude that Pxaaa1p plays a direct role in peroxisomal protein import and is required for PTS1 receptor activity.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Amino Acid Sequence Base Sequence Biological Transport Cells, Cultured Chromosome Mapping Chromosomes, Human, Pair 6 Cytoplasm/enzymology DNA, Complementary Genetic Complementation Test Humans Molecular Sequence Data Mutation Peroxisomal Disorders/genetics Peroxisome-Targeting Signal 1 Receptor Proteins/metabolism Receptors, Cytoplasmic and Nuclear/genetics
Chemicals
DNA, Complementary Peroxisome-Targeting Signal 1 Receptor Proteins Receptors, Cytoplasmic and Nuclear Adenosine Triphosphatases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yahraus T
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Braverman N
Dodt G
Kalish J E
Morrell J C
Moser H W
Valle D
Gould S J
References (62)
62 references, click to expand
  1. MSF, a novel cytoplasmic chaperone which functions in precursor targeting to mitochondria.
    EMBO J. 1994 Nov 1;13(21):5146-54 PMID: 7957079
  2. Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5419-23 PMID: 2568633
  3. Antibodies directed against the peroxisomal targeting signal of firefly luciferase recognize multiple mammalian peroxisomal proteins.
    J Cell Biol. 1990 Jan;110(1):27-34 PMID: 1688562
  4. Differential plasmid rescue from transgenic mouse DNAs into Escherichia coli methylation-restriction mutants.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4645-9 PMID: 2162051
  5. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  6. PAS1, a yeast gene required for peroxisome biogenesis, encodes a member of a novel family of putative ATPases.
    Cell. 1991 Feb 8;64(3):499-510 PMID: 1825027
  7. Restoration by a 35K membrane protein of peroxisome assembly in a peroxisome-deficient mammalian cell mutant.
    Nature. 1991 Mar 7;350(6313):77-81 PMID: 1750930
  8. A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase.
    EMBO J. 1991 Nov;10(11):3255-62 PMID: 1680677
  9. Amino-terminal presequence of the precursor of peroxisomal 3-ketoacyl-CoA thiolase is a cleavable signal peptide for peroxisomal targeting.
    Biochem Biophys Res Commun. 1991 Dec 31;181(3):947-54 PMID: 1764107
  10. Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene.
    Genomics. 1992 Jun;13(2):389-94 PMID: 1612597
  11. The Pas2 protein essential for peroxisome biogenesis is related to ubiquitin-conjugating enzymes.
    Nature. 1992 Sep 3;359(6390):73-6 PMID: 1326082
  12. Mutational analysis of the consensus nucleotide binding sequences in the rat liver mitochondrial ATP synthase beta-subunit.
    J Biol Chem. 1992 Oct 5;267(28):20331-8 PMID: 1400352
  13. Import of proteins into peroxisomes and other microbodies.
    Biochem J. 1992 Sep 15;286 ( Pt 3):657-69 PMID: 1417723
  14. Development of the yeast Pichia pastoris as a model organism for a genetic and molecular analysis of peroxisome assembly.
    Yeast. 1992 Aug;8(8):613-28 PMID: 1441741
  15. Regulation of translation in eukaryotic systems.
    Annu Rev Cell Biol. 1992;8:197-225 PMID: 1335743
  16. Two independent peroxisomal targeting signals in catalase A of Saccharomyces cerevisiae.
    J Cell Biol. 1993 Feb;120(3):665-73 PMID: 8425895
  17. Cytosol-dependent peroxisomal protein import in a permeabilized cell system.
    J Cell Biol. 1993 Feb;120(3):675-85 PMID: 8425896
  18. Import of firefly luciferase into mammalian peroxisomes in vivo requires nucleoside triphosphates.
    Exp Cell Res. 1993 Mar;205(1):66-75 PMID: 8453999
  19. Standardization of complementation grouping of peroxisome-deficient disorders and the second Zellweger patient with peroxisomal assembly factor-1 (PAF-1) defect.
    Am J Hum Genet. 1993 Apr;52(4):843-4 PMID: 7681622
  20. The pas8 mutant of Pichia pastoris exhibits the peroxisomal protein import deficiencies of Zellweger syndrome cells--the PAS8 protein binds to the COOH-terminal tripeptide peroxisomal targeting signal, and is a member of the TPR protein family.
    J Cell Biol. 1993 May;121(4):761-74 PMID: 8098333
  21. Two complementary approaches to study peroxisome biogenesis in Saccharomyces cerevisiae: forward and reversed genetics.
    Biochimie. 1993;75(3-4):209-24 PMID: 8507683
  22. NIGMS human/rodent somatic cell hybrid mapping panels 1 and 2.
    Genomics. 1993 May;16(2):311-4 PMID: 8314568
  23. Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library.
    Nat Genet. 1993 Aug;4(4):373-80 PMID: 8401585
  24. Cloning and characterization of PAS5: a gene required for peroxisome biogenesis in the methylotrophic yeast Pichia pastoris.
    J Cell Biol. 1993 Nov;123(3):535-48 PMID: 8227124
  25. Presence of cytoplasmic factors functional in peroxisomal protein import implicates organelle-associated defects in several human peroxisomal disorders.
    J Clin Invest. 1993 Nov;92(5):2462-8 PMID: 7693762
  26. Sequence of the PAS8 gene, the product of which is essential for biogenesis of peroxisomes in Saccharomyces cerevisiae.
    Biochim Biophys Acta. 1993 Nov 16;1216(2):325-8 PMID: 8241279
  27. PAS10 is a tetratricopeptide-repeat protein that is essential for the import of most matrix proteins into peroxisomes of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11782-6 PMID: 8265627
  28. PAY4, a gene required for peroxisome assembly in the yeast Yarrowia lipolytica, encodes a novel member of a family of putative ATPases.
    J Biol Chem. 1994 Jan 7;269(1):556-66 PMID: 8276851
  29. Mutational analysis of the N-terminal topogenic signal of watermelon glyoxysomal malate dehydrogenase using the heterologous host Hansenula polymorpha.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3151-5 PMID: 8159718
  30. PxF, a prenylated protein of peroxisomes.
    J Biol Chem. 1994 May 13;269(19):14182-90 PMID: 8188701
  31. Differential protein import deficiencies in human peroxisome assembly disorders.
    J Cell Biol. 1994 May;125(4):755-67 PMID: 7910611
  32. Involvement of 70-kD heat-shock proteins in peroxisomal import.
    J Cell Biol. 1994 Jun;125(5):1037-46 PMID: 8195287
  33. The Pichia pastoris PAS4 gene encodes a ubiquitin-conjugating enzyme required for peroxisome assembly.
    J Biol Chem. 1994 Aug 26;269(34):21835-44 PMID: 8063827
  34. Maps from two interspecific backcross DNA panels available as a community genetic mapping resource.
    Mamm Genome. 1994 May;5(5):253-74 PMID: 8075499
  35. Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10541-5 PMID: 7937990
  36. PAS7 encodes a novel yeast member of the WD-40 protein family essential for import of 3-oxoacyl-CoA thiolase, a PTS2-containing protein, into peroxisomes.
    EMBO J. 1994 Oct 17;13(20):4908-18 PMID: 7957058
  37. PEB1 (PAS7) in Saccharomyces cerevisiae encodes a hydrophilic, intra-peroxisomal protein that is a member of the WD repeat family and is essential for the import of thiolase into peroxisomes.
    J Cell Biol. 1995 Apr;129(1):65-80 PMID: 7535304
  38. Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor.
    J Biol Chem. 1995 Mar 31;270(13):7731-6 PMID: 7706321
  39. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders.
    Nat Genet. 1995 Feb;9(2):115-25 PMID: 7719337
  40. Effect of site-directed mutagenesis of conserved lysine residues upon Pas1 protein function in peroxisome biogenesis.
    Yeast. 1994 Dec;10(12):1613-20 PMID: 7725796
  41. Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders.
    J Cell Biol. 1995 Jul;130(1):51-65 PMID: 7790377
  42. Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups.
    J Pediatr. 1995 Jul;127(1):13-22 PMID: 7541833
  43. The Hansenula polymorpha PER3 gene is essential for the import of PTS1 proteins into the peroxisomal matrix.
    J Biol Chem. 1995 Jul 21;270(29):17229-36 PMID: 7615522
  44. Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope.
    Curr Biol. 1995 Apr 1;5(4):383-92 PMID: 7627554
  45. A 200-amino acid ATPase module in search of a basic function.
    Bioessays. 1995 Jul;17(7):639-50 PMID: 7646486
  46. Identification of three distinct peroxisomal protein import defects in patients with peroxisome biogenesis disorders.
    J Cell Sci. 1995 May;108 ( Pt 5):1817-29 PMID: 7544797
  47. Membrane fusion and the cell cycle: Cdc48p participates in the fusion of ER membranes.
    Cell. 1995 Sep 22;82(6):885-93 PMID: 7553849
  48. Formation of the peroxisome lumen is abolished by loss of Pichia pastoris Pas7p, a zinc-binding integral membrane protein of the peroxisome.
    Mol Cell Biol. 1995 Nov;15(11):6406-19 PMID: 7565793
  49. Import of stably folded proteins into peroxisomes.
    Mol Biol Cell. 1995 Jun;6(6):675-83 PMID: 7579687
  50. When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells.
    RNA. 1995 Jul;1(5):453-65 PMID: 7489507
  51. Role of the PAS1 gene of Pichia pastoris in peroxisome biogenesis.
    J Cell Biol. 1994 Dec;127(5):1259-73 PMID: 7962088
  52. The tetratricopeptide repeat-domain of the PAS10 protein of Saccharomyces cerevisiae is essential for binding the peroxisomal targeting signal-SKL.
    Biochem Biophys Res Commun. 1994 Nov 15;204(3):1016-22 PMID: 7980572
  53. The N-terminus of amine oxidase of Hansenula polymorpha contains a peroxisomal targeting signal.
    FEBS Lett. 1995 Jan 3;357(2):115-20 PMID: 7805876
  54. The Hansenula polymorpha PER8 gene encodes a novel peroxisomal integral membrane protein involved in proliferation.
    J Cell Biol. 1995 Feb;128(3):307-19 PMID: 7844145
  55. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
    EMBO J. 1982;1(8):945-51 PMID: 6329717
  56. Proton ionophores prevent assembly of a peroxisomal protein.
    Cell. 1987 Jan 16;48(1):165-73 PMID: 3539364
  57. Mechanism of protein translocation across the endoplasmic reticulum membrane.
    Annu Rev Cell Biol. 1986;2:499-516 PMID: 3030381
  58. Translocation of acyl-CoA oxidase into peroxisomes requires ATP hydrolysis but not a membrane potential.
    J Cell Biol. 1987 Dec;105(6 Pt 2):2915-22 PMID: 3693402
  59. Peroxisomal membrane ghosts in Zellweger syndrome--aberrant organelle assembly.
    Science. 1988 Mar 25;239(4847):1536-8 PMID: 3281254
  60. Acyl-CoA oxidase contains two targeting sequences each of which can mediate protein import into peroxisomes.
    EMBO J. 1988 Apr;7(4):1167-73 PMID: 3402435
  61. A conserved tripeptide sorts proteins to peroxisomes.
    J Cell Biol. 1989 May;108(5):1657-64 PMID: 2654139
  62. An oligomeric protein is imported into peroxisomes in vivo.
    J Cell Biol. 1994 Dec;127(5):1245-57 PMID: 7962087
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-06-17
Pages
2914-23
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450231
Subset
IM
Grants
NIDDK NIH HHS · DK45787 · United States
NICHD NIH HHS · HD10981 · United States
NIGMS NIH HHS · T32GM07471 · United States
Databases
GENBANK
U56602
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2