Crystallization (Comment) | Organism |
---|---|
analysis of the crystal structures of the extreme N-terminal part of murine Pex1p exposed a double-psi-beta-barrel fold with similarities to adaptor binding domains of p97 and NSF | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Escherichia coli | 5829 | - |
cytosol | the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane | Saccharomyces cerevisiae | 5829 | - |
additional information | four Lon isoforms localize to mitochondria, plastids and peroxisomes.The peroxisome specific enzyme is Lon2, which carries a PTS1-signal | Arabidopsis thaliana | - |
- |
additional information | presence of two Lon isoforms with one of them located in the peroxisomal matrix | Ogataea angusta | - |
- |
additional information | the AAAdomains of Pex6p seem to influence the Pex6p/Pex15p-interaction and thereby regulate the recruitment of the cytosolic AAA-complex to the peroxisomal membrane, although in opposite fashion. In particular, ATP-binding to D1 of Pex6p stimulates association of the AAA-complex with Pex15p at the peroxisomal membrane while ATP-hydrolysis at D2 seems to trigger the release of the AAA-complex from Pex15p and thus from the membrane | Saccharomyces cerevisiae | - |
- |
additional information | the tail-anchored protein Pex15p in yeast functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex15p and mediates the attachment of the Pex1p-Pex6p complex to the membrane | Saccharomyces cerevisiae | - |
- |
additional information | the tail-anchored protein Pex26p in humans functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex26p and mediates the attachment of the Pex1p-Pex6p complex to the membrane | Homo sapiens | - |
- |
additional information | the tail-anchored protein Pex26p in humans functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex26p and mediates the attachment of the Pex1pPex6p complex to the membrane | Homo sapiens | - |
- |
peroxisomal membrane | the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane. Association of this complex with the peroxisomal membrane is mediated by binding to Pex15p. The predominant part of the tail anchored protein Pex15p faces the cytosol and mediates the peroxisomal membrane association of the AAA-complex via a direct interaction with the N-terminal domain of Pex6p, assembly of the Pex1p/Pex6p-complex and recruitment to the peroxisomal membrane | Saccharomyces cerevisiae | 5778 | - |
peroxisomal membrane | the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane. Association of this complex with the peroxisomal membrane is mediated by binding to Pex15p. The predominant part of the tail-anchored protein Pex15p faces the cytosol and mediates the peroxisomal membrane association of the AAA-complex via a direct interaction with the N-terminal domain of Pex6p, assembly of the Pex1p/Pex6p-complex and recruitment to the peroxisomal membrane | Saccharomyces cerevisiae | 5778 | - |
peroxisome | Pex1p is targeted to peroxisomes in a manner dependent on ATP hydrolysis, while Pex6p targeting requires ATP but not its hydrolysis | Saccharomyces cerevisiae | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases | Penicillium chrysogenum | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases, peroxisomal matrix isozyme | Ogataea angusta | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane | Homo sapiens | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane | Saccharomyces cerevisiae | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane | Mus musculus | 5777 | - |
peroxisome | structural organization and localization of peroxisomal AAA+ ATPases. The peroxisome specific isozyme is Lon2, which carries a PTS1-signal | Arabidopsis thaliana | 5777 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Arabidopsis thaliana | |
Mg2+ | required | Escherichia coli | |
Mg2+ | required | Homo sapiens | |
Mg2+ | required | Saccharomyces cerevisiae | |
Mg2+ | required | Ogataea angusta | |
Mg2+ | required | Penicillium chrysogenum | |
Mg2+ | required | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O | Arabidopsis thaliana | - |
ADP + phosphate | - |
? | |
ATP + H2O | Escherichia coli | - |
ADP + phosphate | - |
? | |
ATP + H2O | Homo sapiens | - |
ADP + phosphate | - |
? | |
ATP + H2O | Saccharomyces cerevisiae | - |
ADP + phosphate | - |
? | |
ATP + H2O | Ogataea angusta | - |
ADP + phosphate | - |
? | |
ATP + H2O | Penicillium chrysogenum | - |
ADP + phosphate | - |
? | |
ATP + H2O | Mus musculus | - |
ADP + phosphate | - |
? | |
additional information | Saccharomyces cerevisiae | model of Pex5p export by threading through the central Pex1p-Pex6p pore, overview | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Arabidopsis thaliana | O64948 | Lon2 | - |
Escherichia coli | P0A9M0 | - |
- |
Homo sapiens | O43933 | PEX1; gene PEX1 | - |
Homo sapiens | Q13608 | PEX6; gene PEX6 | - |
Mus musculus | Q5BL07 | PEX1 | - |
Mus musculus | Q99LC9 | PEX6 | - |
Ogataea angusta | Q2V573 | - |
- |
Penicillium chrysogenum | B6HJQ3 | - |
- |
Saccharomyces cerevisiae | P24004 | gene PEX1 | - |
Saccharomyces cerevisiae | P24004 | PEX1 | - |
Saccharomyces cerevisiae | P33760 | gene PEX6 | - |
Saccharomyces cerevisiae | P33760 | PEX6 | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O | - |
Arabidopsis thaliana | ADP + phosphate | - |
? | |
ATP + H2O | - |
Escherichia coli | ADP + phosphate | - |
? | |
ATP + H2O | - |
Homo sapiens | ADP + phosphate | - |
? | |
ATP + H2O | - |
Saccharomyces cerevisiae | ADP + phosphate | - |
? | |
ATP + H2O | - |
Ogataea angusta | ADP + phosphate | - |
? | |
ATP + H2O | - |
Penicillium chrysogenum | ADP + phosphate | - |
? | |
ATP + H2O | - |
Mus musculus | ADP + phosphate | - |
? | |
additional information | model of Pex5p export by threading through the central Pex1p-Pex6p pore, overview | Saccharomyces cerevisiae | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure | Homo sapiens |
heterohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure | Saccharomyces cerevisiae |
heterohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure | Mus musculus |
homohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment | Arabidopsis thaliana |
homohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment | Escherichia coli |
homohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment | Ogataea angusta |
homohexamer | AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment | Penicillium chrysogenum |
More | since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins | Mus musculus |
More | since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins. Under ATP depletion, Pex6p remains at the peroxisomal membrane, whereas Pex1p is released to the cytosol, probably as homotrimeric version | Homo sapiens |
More | when the yeast Pex1p-Pex6p complex disassembles under ATP depleting conditions, Pex1p adopts a homotrimeric conformation, while Pex6p is monomeric. Since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins | Saccharomyces cerevisiae |
Synonyms | Comment | Organism |
---|---|---|
APEM10 | - |
Arabidopsis thaliana |
lon | - |
Arabidopsis thaliana |
lon | - |
Escherichia coli |
lon | - |
Ogataea angusta |
lon | - |
Penicillium chrysogenum |
lon protease | - |
Arabidopsis thaliana |
lon protease | - |
Escherichia coli |
lon protease | - |
Ogataea angusta |
lon protease | - |
Penicillium chrysogenum |
lon2 | - |
Arabidopsis thaliana |
peroxisomal Lon-protease | - |
Arabidopsis thaliana |
peroxisomal Lon-protease | - |
Escherichia coli |
peroxisomal Lon-protease | - |
Ogataea angusta |
peroxisomal Lon-protease | - |
Penicillium chrysogenum |
Pex1p | - |
Homo sapiens |
Pex1p | - |
Saccharomyces cerevisiae |
Pex1p | - |
Mus musculus |
Pex1p-Pex6p complex | - |
Saccharomyces cerevisiae |
Pex1p/Pex6p | - |
Homo sapiens |
Pex1p/Pex6p | - |
Saccharomyces cerevisiae |
Pex1p/Pex6p | - |
Mus musculus |
Pex6p | - |
Homo sapiens |
Pex6p | - |
Saccharomyces cerevisiae |
Pln | - |
Penicillium chrysogenum |
Organism | Comment | Expression |
---|---|---|
Saccharomyces cerevisiae | binding of Pex15p to the Pex1p-Pex6p complex downregulates the ATPase activity of the AAA+-complex, possibly by influencing the D2 AAA+-domain of Pex1p | down |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase | Arabidopsis thaliana |
evolution | the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase | Ogataea angusta |
evolution | the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase | Penicillium chrysogenum |
evolution | the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase. Based on the domain composition and sequence characteristic of the domains, the Lon-proteases are subdivided into two classes, LonA and LonB. The LonA subfamily are soluble enzymes,which function in the bacterial cytosol and the mitochondrial matrix, whereas LonB predominates in Archaea | Escherichia coli |
evolution | the enzyme belongs to the AAA+ ATPase family. AAA-proteins belong to the class of P-loop NTPases defined by conserved motifs for NTP-binding (Walker A motif) and hydrolysis (Walker B motif) which are assisted by Mg2+ as cofactor. Pex1p and Pex6p are evolutionary related to Cdc48p/p97 | Saccharomyces cerevisiae |
evolution | the enzyme belongs to the AAA+ ATPase superfamily | Homo sapiens |
evolution | the enzyme belongs to the AAA+ ATPase superfamily | Saccharomyces cerevisiae |
evolution | the enzyme belongs to the AAA+ ATPase superfamily | Mus musculus |
malfunction | a deletion of peroxisomal Lon results in a specific growth defect on media containing oleic acid as a sole carbon source, conditions which require peroxisomal enzymes of the beta-oxidation pathway, the growth defect is accompanied by the formation of protein aggregates in the peroxisomal matrix | Penicillium chrysogenum |
malfunction | a Lon protease deletion strain does not display a growth defect but a decreased viability of the cells | Ogataea angusta |
malfunction | Lon2 absence leads to accumulation of enzymes in peroxisomes and results in an accelerated peroxisome degradation by pexophagy | Arabidopsis thaliana |
malfunction | mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are themost common cause of the Zellweger spectrum diseases, the by far most abundant Pex1pG843D variation impairs the binding between Pex1p and Pex6p | Homo sapiens |
malfunction | the PEX6-deletion strain has the most pronounced survival defects of all strains affected in peroxisome function | Saccharomyces cerevisiae |
metabolism | the enzyme is involved in peroxisome biogenesis | Arabidopsis thaliana |
metabolism | the enzyme is involved in peroxisome biogenesis | Escherichia coli |
metabolism | the enzyme is involved in peroxisome biogenesis | Homo sapiens |
metabolism | the enzyme is involved in peroxisome biogenesis | Saccharomyces cerevisiae |
metabolism | the enzyme is involved in peroxisome biogenesis | Ogataea angusta |
metabolism | the enzyme is involved in peroxisome biogenesis | Penicillium chrysogenum |
metabolism | the enzyme is involved in peroxisome biogenesis | Mus musculus |
metabolism | the enzyme is involved in peroxisome biogenesis, proteins that play a role in peroxisome biogenesis are collectively called peroxins. Function of Pex1p and Pex6p in peroxisomal matrix protein import, overview | Saccharomyces cerevisiae |
additional information | structural organization and localization of peroxisomal AAA+ ATPases | Arabidopsis thaliana |
additional information | structural organization and localization of peroxisomal AAA+ ATPases | Escherichia coli |
additional information | structural organization and localization of peroxisomal AAA+ ATPases | Ogataea angusta |
additional information | structural organization and localization of peroxisomal AAA+ ATPases | Penicillium chrysogenum |
additional information | structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview | Homo sapiens |
additional information | structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview | Saccharomyces cerevisiae |
additional information | structure-function analysis. AAA-peroxins defective in ATP-hydrolysis of D1 are at least partially functional. In contrast, ATP-hydrolysis of the conserved AAA-domains (D2) of both AAA-peroxins is essential for their function. The conserved D2-domains of Pex1p and Pex6p require hydrolysis of ATP for their function in peroxisome biogenesis, indicating that they may provide the driving force for conformational changes triggered by the AAA-peroxins | Saccharomyces cerevisiae |
additional information | structure-function analysis. The D1 of Pex6p does not contain a functional Walker B motif for ATP hydrolysis. AAA-peroxins defective in ATP-hydrolysis of D1 are at least partially functional. In contrast, ATP-hydrolysis of the conserved AAA-domains (D2) of both AAA-peroxins is essential for their function. The conserved D2-domains of Pex1p and Pex6p require hydrolysis of ATP for their function in peroxisome biogenesis, indicating that they may providethe driving force for conformational changes triggered by the AAA-peroxins | Saccharomyces cerevisiae |
additional information | the murine Pex1p N-terminal domain lacks hydrophobic amino acids. Structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview | Mus musculus |
physiological function | Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex1p in peroxisomal matrix protein import, overview | Homo sapiens |
physiological function | Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex1p/Pex6p in peroxisomal matrix protein import, overview | Homo sapiens |
physiological function | Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex6p in peroxisomal matrix protein import, overview | Saccharomyces cerevisiae |
physiological function | Pex6p functions together with Pex1p in peroxisome biogenesis | Mus musculus |
physiological function | the enzyme is essentially involved in peroxisome biogenesis, Pex1p provides the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle | Saccharomyces cerevisiae |
physiological function | the enzyme is essentially involved in peroxisome biogenesis, Pex6p provides the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle. Pex6p might also have additional functions that appear not to be related to peroxisomes, yeast Pex6p acts as a suppressor for aging defects in mitochondria. Overexpression of Pex6p, but not of Pex1p, restores the import defect of mutant ATP2, the gene encoding the beta-subunit of mitochondrial F1,F0-ATPase, into mitochondria. Function for Pex6p in the prevention of necrotic cell death in yeast | Saccharomyces cerevisiae |
physiological function | the enzyme is involved in peroxisome biogenesis abd associated with peroxisomal quality control. The Lon protease functions in the degradation of mutated or abnormal proteins as well as short-lived regulatory proteins, in particular those produced under stress conditions | Escherichia coli |
physiological function | the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control | Penicillium chrysogenum |
physiological function | the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control. Lon2 is required for the elimination of unnecessary proteins during the functional transition of glyoxysomes to peroxisomes | Arabidopsis thaliana |
physiological function | the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control. The peroxisomal Lon and autophagy function together in peroxisomal quality control | Ogataea angusta |