PEX19 binds class I peroxisomal membrane proteins

Stable Identifier
Reaction [binding]
Homo sapiens
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In the cytosol, PEX19 binds newly synthesized class I peroxisomal membrane proteins (Sacksteder et al. 2000, Fransen et al. 2001, Jones et al. 2004, reviewed in Fujiki et al. 2006). The C-terminal region and a conserved N-terminal helical segment of PEX19 bind to peroxisomal membrane proteins (Fransen et al. 2005, Schueller et al. 2010) and PEX19 acts both as a chaperone and as an import receptor (Jones et al. 2004). PEX19 is farnesylated (Götte et al. 1998, Sacksteder et al. 2000, Vastiau et al. 2006) and the farnesyl group is buried in a hydrophobic cavity which alters the conformation of PEX19 to yield two hydrophobic pockets involved in binding peroxisomal membrane proteins (Emmanouilidis et al. 2017). The number of positively charged amino acid residues in the transmembrane domain of the PMP appears to determine binding by PEX19 and, hence, targeting to the peroxisomal membrane protein (Costello et al. 2017).
Class I membrane proteins are inserted into the peroxisomal membrane after peroxisomal progenitors have budded from the endoplasmic reticulum (Jones et al. 2004). Human class I peroxisomal membrane proteins that are bound by PEX19 include PEX10 (Sacksteder et al. 2000), PEX11B (Fransen et al. 2005), PEX12 (Sacksteder et al. 2000, Fransen et al. 2001, Fransen et al. 2005), PEX13 (Sacksteder et al. 2000, Fransen et al. 2001, Fransen et al. 2005, Vastiau et al. 2006, Liu et al. 2016), PEX14 (Sacksteder et al. 2000, Fransen et al. 2005, Vastiau et al. 2006), PEX16 (Fransen et al. 2001, Fransen et al. 2005, Matsuzono and Fujiki 2006, Schueller et al. 2010, Yagita et al. 2013, Liu et al. 2016), ), PEX26 (Fransen et al. 2005, Matsuzono and Fujiki 2006), ABCD1 (ALDP, Mayerhofer et al. 2002, Halbach et al. 2005), ABCD2 (ALDRP, Mayerhofer et al. 2002), ABCD3 (PMP70, Sacksteder et al. 2000, Mayerhofer et al. 2002), PXMP2 (PMP22, Jones et al. 2001, Brosius et al. 2002), PXMP4 (PMP24, Pinto et al. 2006), SLC25A17 (PMP34, Sacksteder et al. 2000, Liu et al. 2016), ATAD1 (Liu et al. 2016), FIS1 (Delille and Schrader 2008), and GDAP1 (Huber et al. 2013).

Literature References
PubMed ID Title Journal Year
23628762 Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission

Huber, N, Guimaraes, S, Schrader, M, Suter, U, Niemann, A

EMBO Rep. 2013
20531392 The peroxisomal receptor Pex19p forms a helical mPTS recognition domain

Schueller, N, Holton, SJ, Fodor, K, Milewski, M, Konarev, P, Stanley, WA, Wolf, J, Erdmann, R, Schliebs, W, Song, YH, Wilmanns, M

EMBO J. 2010
15781447 Function of the PEX19-binding site of human adrenoleukodystrophy protein as targeting motif in man and yeast. PMP targeting is evolutionarily conserved

Halbach, A, Lorenzen, S, Landgraf, C, Volkmer-Engert, R, Erdmann, R, Rottensteiner, H

J. Biol. Chem. 2005
16791427 Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells

Vastiau, IM, Anthonio, EA, Brams, M, Brees, C, Young, SG, Van de Velde, S, Wanders, RJ, Mannaerts, GP, Baes, M, Van Veldhoven, PP, Fransen, M

Cell. Mol. Life Sci. 2006
23460677 Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway

Yagita, Y, Hiromasa, T, Fujiki, Y

J. Cell Biol. 2013
11453642 Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal integral membrane protein (PMP70) to peroxisomes

Biermanns, M, Gärtner, J

Biochem. Biophys. Res. Commun. 2001
28281558 Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19

Emmanouilidis, L, Schütz, U, Tripsianes, K, Madl, T, Radke, J, Rucktäschel, R, Wilmanns, M, Schliebs, W, Erdmann, R, Sattler, M

Nat Commun 2017
16980692 The import competence of a peroxisomal membrane protein is determined by Pex19p before the docking step

Pinto, MP, Grou, CP, Alencastre, IS, Oliveira, ME, Sá-Miranda, C, Fransen, M, Azevedo, JE

J. Biol. Chem. 2006
18782765 Targeting of hFis1 to peroxisomes is mediated by Pex19p

Delille, HK, Schrader, M

J. Biol. Chem. 2008
15713480 Analysis of human Pex19p's domain structure by pentapeptide scanning mutagenesis

Fransen, M, Vastiau, I, Brees, C, Brys, V, Mannaerts, GP, Van Veldhoven, PP

J. Mol. Biol. 2005
12751901 The peroxisomal membrane targeting elements of human peroxin 2 (PEX2)

Biermanns, M, von Laar, J, Brosius, U, Gärtner, J

Eur. J. Cell Biol. 2003
28325759 Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells

Costello, JL, Castro, IG, Camões, F, Schrader, TA, McNeall, D, Yang, J, Giannopoulou, EA, Gomes, S, Pogenberg, V, Bonekamp, NA, Ribeiro, D, Wilmanns, M, Jedd, G, Islinger, M, Schrader, M

J. Cell. Sci. 2017
11390669 Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences

Fransen, M, Wylin, T, Brees, C, Mannaerts, GP, Van Veldhoven, PP

Mol. Cell. Biol. 2001
14709540 PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins

Jones, JM, Morrell, JC, Gould, SJ

J. Cell Biol. 2004
9418908 Pex19p, a farnesylated protein essential for peroxisome biogenesis

Götte, K, Girzalsky, W, Linkert, M, Baumgart, E, Kammerer, S, Kunau, WH, Erdmann, R

Mol. Cell. Biol. 1998
11590176 Two different targeting signals direct human peroxisomal membrane protein 22 to peroxisomes

Brosius, U, Dehmel, T, Gärtner, J

J. Biol. Chem. 2002
17069900 Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions

Fujiki, Y, Matsuzono, Y, Matsuzaki, T, Fransen, M

Biochim. Biophys. Acta 2006
10704444 PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis

Sacksteder, KA, Jones, JM, South, ST, Li, X, Liu, Y, Gould, SJ

J Cell Biol 2000
11402059 Multiple distinct targeting signals in integral peroxisomal membrane proteins

Jones, JM, Morrell, JC, Gould, SJ

J. Cell Biol. 2001
26777132 Assembly of Peroxisomal Membrane Proteins via the Direct Pex19p-Pex3p Pathway

Liu, Y, Yagita, Y, Fujiki, Y

Traffic 2016
16280322 In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p

Matsuzono, Y, Fujiki, Y

J. Biol. Chem. 2006
11883941 Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly

Mayerhofer, PU, Kattenfeld, T, Roscher, AA, Muntau, AC

Biochem. Biophys. Res. Commun. 2002
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