Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Identification and characterization of the human orthologue of yeast Pex14p.
-
HsPex14p identified as a carbonate-resistant peroxisomal membrane protein that binds PEX5 and is required for peroxisomal matrix protein import.
"HsPex14p is a carbonate-resistant peroxisomal membrane protein with its C terminus exposed to the cytosol"
PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import.
PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.
-
PEX19 binds PEX14 as part of its broad PMP-binding activity.
"PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes"
The di-aromatic pentapeptide repeats of the human peroxisome import receptor PEX5 are separate high affinity binding sites for the peroxisomal membrane protein PEX14.
-
Each of the seven WxxxF/Y motifs in PEX5 binds PEX14 N-terminal domain with nanomolar affinity, establishing PEX14 as the primary docking factor.
"each of the seven di-aromatic pentapeptides of human PEX5 interacts separately at the same binding site in the N terminus of PEX14 with equilibrium dissociation constants in the low nanomolar range"
Identification of a novel human peroxisomal 2,4-dienoyl-CoA reductase related protein using the M13 phage protein VI phage display technology.
NAPP2, a peroxisomal membrane protein, is also a transcriptional corepressor.
-
PEX14 (NAPP2) reported to interact with HDAC1 and inhibit p45/NF-E2 transcription. Single study; physiological relevance for a peroxisomal membrane protein is uncertain.
"ectopically expressed NAPP2 inhibited p45-directed transcriptional activation. Furthermore, NAPP2 functions as a corepressor and interacts specifically with histone deacetylase l (HDAC1)"
Analysis of mammalian peroxin interactions using a non-transcription-based bacterial two-hybrid assay.
-
PEX14 interacts with PEX5, PEX13, PEX19, and itself (predominantly as a dimer). The PEX5-PEX13 interaction is bridged by PEX14.
"the Pex5p-Pex13p interaction is bridged by Pex14p and that the latter molecule exists predominantly as a dimer in vivo"
Mammalian Pex14p: membrane topology and characterisation of the Pex14p-Pex14p interaction.
-
PEX14 N-terminal ~130 residues are protected by the peroxisomal membrane. PEX14 forms homo-oligomers of variable stoichiometry via aa 147-278.
"Heterologous expressed Pex14p was found to be a homopolymer of variable stoichiometry. Finally, in vitro binding assays indicate that homopolymerisation of Pex14p involves a domain comprising amino acid residues 147-278 of this peroxin"
Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene.
-
PEX14 p.Q185X nonsense mutation causes Zellweger syndrome (new complementation group). PEX14 is essential for both PTS1 and PTS2 import in humans.
"PEX14 is a key component of the peroxisomal import machinery and may be the initial docking site for the two import receptors PEX5 and PEX7"
Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance.
Peroxisomes in human and mouse testis: differential expression of peroxisomal proteins in germ cells and distinct somatic cell types of the testis.
Comparison of the PTS1- and Rab8b-binding properties of Pex5p and Pex5Rp/TRIP8b.
Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19.
-
NMR structure of PEX14 N-terminal domain in complex with PEX5 and PEX19. PEX5 and PEX19 bind competitively to the same surface with opposite directionality.
"Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite directionality"
Solution structure of human Pex5.Pex14.PTS1 protein complexes obtained by small angle X-ray scattering.
Defining the membrane proteome of NK cells.
The Peroxisomal Targeting Signal 1 in sterol carrier protein 2 is autonomous and essential for receptor recognition.
PEX14 is required for microtubule-based peroxisome motility in human cells.
-
PEX14 directly binds tubulin through its N-terminal domain. PEX14-deficient cells lose microtubule-based peroxisome motility. PEX14 is a multi-tasking protein serving both import and motility functions.
"tubulin was discovered to be the major PEX14-associated protein, and direct binding of the proteins was demonstrated"
PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14.
-
PEX14 N-terminal domain disrupts PEX5-catalase interaction, demonstrating PEX14's role in cargo release at the DTM.
"the PEX5-catalase interaction is disrupted by the N-terminal domain of PEX14, a component of the docking/translocation machinery"
A novel Pex14 protein-interacting site of human Pex5 is critical for matrix protein import into peroxisomes.
-
Novel LVXEF motif in PEX5 binds PEX14 N-terminal domain with faster dissociation kinetics than WxxxF/Y motifs. May represent initial tethering site.
"The novel motif composes the sequence LVAEF with the evolutionarily conserved consensus sequence LVXEF"
Mechanistic insights into PTS2-mediated peroxisomal protein import: the co-receptor PEX5L drastically increases the interaction strength between the cargo protein and the receptor PEX7.
ATM functions at the peroxisome to induce pexophagy in response to ROS.
-
PEX14 protein levels decrease during ROS-induced pexophagy. PEX14 used as a marker of peroxisome degradation, not an active participant in ROS sensing.
"ATM signalling activates ULK1 and inhibits mTORC1 to induce autophagy. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141"
The peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo.
-
DTM is a large cavity-forming assembly. PEX14 is a major component. PEX5-PEX14 interaction is stable at pH 11.5. Multiple PEX5 domains interact with DTM in a 'fuzzy' manner.
"the interaction between PEX5 and PEX14, a major DTM component, is stable at pH 11.5"
LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
Maximizing binary interactome mapping with a minimal number of assays.
A reference map of the human binary protein interactome.
Peroxisome biogenesis initiated by protein phase separation.
-
Pex14 forms foci during cargo import events, consistent with transient channel formation through liquid-liquid phase separation with Pex5-cargo.
"cargo import correlates with transient focusing of GFP-Pex13 and GFP-Pex14 on the peroxisome membrane"
AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.
Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import.
-
First identification of human PEX14 as a peroxisomal membrane protein that binds PEX5 and PEX13, directly required for peroxisomal protein import.
"Recombinant Pex14p was specifically recognized by the "import inhibiting" ab-MF3 and bound Pex5p and the Src homology 3 (SH3) domain of Pex13p in ligand blots"
PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3
PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11
Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module)
PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11
PEX1:PEX6:PEX26:ZFAND6 dissociates Ub:PEX5L and PEX7 from PEX14:PEX13:PEX2:PEX10:PEX12 and translocates PEX5L and PEX7 from the peroxisomal membrane to the cytosol
Cargo of PEX5L:PEX7 translocates from the cytosol to the peroxisomal matrix
PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6
PEX2:PEX10:PEX12 binds PEX5L (in PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12) and Ub:UBE2D1,2,3
PEX2:PEX10:PEX12:Ub:PEX5S,L:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6
PEX3:PEX19:class I PMP dissociates
PEX19:class I PMP binds PEX3
PEX19 binds class I peroxisomal membrane proteins