PEX11A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX11A is an integral peroxisomal membrane protein with two transmembrane helices, confirmed by multiple independent experimental studies. IBA annotation is phylogenetically well-supported across the PEX11 family. Reason: Peroxisomal membrane localization is the most fundamental and well-established aspect of PEX11A biology. The original cloning paper (PMID:9714566) showed it is an integral peroxisomal membrane protein. Multiple IDA annotations from PMID:9714566, PMID:9792670, and PMID:20826455 also confirm this. The IBA annotation is consistent with all evidence. Supporting Evidence: PMID:9714566 PEX11 encoded a peroxisomal protein Pex11p comprising 247 amino acids, with two transmembrane segments and a dilysine motif at the C-terminus. PMID:9792670 We report here the identification and characterization of two novel human peroxisomal membrane proteins, PEX11alpha and PEX11beta. file:human/PEX11A/PEX11A-deep-research-falcon.md PEX11A is an integral peroxisomal membrane protein that functions as a membrane elongation factor promoting peroxisome proliferation
GO:0016559 peroxisome fission	IBA GO_REF:0000033	ACCEPT	Summary: PEX11A promotes peroxisome elongation (formation of juxtaposed elongated peroxisomes, JEPs) which is a prerequisite step for peroxisome fission/division. IBA annotation is phylogenetically well-supported across the PEX11 family from yeast to humans. Reason: Peroxisome fission is the core biological process for PEX11 family proteins. Koch et al. (2010, PMID:20826455) showed that PEX11 family members drive membrane elongation and coordinate with fission machinery (FIS1, DRP1) for peroxisome division. The IBA reflects a conserved function across eukaryotes. Supporting Evidence: PMID:20826455 Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs),which is evocative of an evolutionary conserved function of these proteins in membrane tubulation. PMID:20826455 Our results demonstrate that PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression.
GO:0005778 peroxisomal membrane	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation for peroxisomal membrane localization. Broader than the IBA annotation but consistent with extensive experimental evidence. Reason: This IEA annotation is redundant with the IBA and multiple IDA annotations for the same term, but is not incorrect. PEX11A is unequivocally a peroxisomal membrane protein. Supporting Evidence: PMID:9714566 PEX11 encoded a peroxisomal protein Pex11p comprising 247 amino acids, with two transmembrane segments and a dilysine motif at the C-terminus.
GO:0007031 peroxisome organization	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation derived from UniProtKB keyword mapping (Peroxisome biogenesis keyword). Peroxisome organization is a parent term of peroxisome fission. PEX11A is involved in peroxisome organization via its membrane elongation/fission role. Reason: This is a broader parent term of peroxisome fission (GO:0016559). Since PEX11A is clearly involved in peroxisome fission, it is also involved in peroxisome organization. The IEA is consistent with the more specific IDA and IBA annotations for peroxisome fission. Supporting Evidence: PMID:9792670 Overexpression of PEX11alpha also induced peroxisome proliferation but at a much lower frequency than PEX11beta in our experimental system.
GO:0016559 peroxisome fission	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro domain mapping (IPR008733, PEX11 domain). Consistent with the core function of PEX11 family proteins in peroxisome fission. Reason: The PEX11 domain (IPR008733/PF05648) is specifically associated with peroxisome fission function. This IEA is consistent with the IBA and IDA annotations for the same term. Supporting Evidence: PMID:20826455 Our results demonstrate that PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression.
GO:0016557 peroxisome membrane biogenesis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IEA annotation from Ensembl Compara ortholog transfer (from rat Pex11a, O70597). PEX11A promotes peroxisomal membrane elongation and contributes to membrane growth during peroxisome division. However, peroxisome membrane biogenesis specifically refers to formation of peroxisome membranes, which is more the domain of PEX3/PEX16/PEX19. Reason: PEX11A is a membrane elongation factor that promotes peroxisome division, not a peroxisome membrane biogenesis factor per se. Peroxisome membrane biogenesis (GO:0016557) implies de novo formation of peroxisomal membranes, which is more specifically the role of PEX3, PEX16, and PEX19. PEX11A acts on pre-existing peroxisomal membranes to promote elongation and division. While there is some overlap, this term is misleading for PEX11A. The more accurate term is peroxisome fission (GO:0016559), already annotated. Supporting Evidence: PMID:9922452 We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.
GO:0005777 peroxisome	IDA PMID:19114594 The peroxisomal membrane protein import receptor Pex3p is di...	ACCEPT	Summary: In Matsuzaki & Fujiki (2008), PEX11A (as HA-Pex11alpha) was used as a control in experiments studying Pex3p targeting. The paper confirmed PEX11A localizes to peroxisomes but PEX11A was not the main subject of study; it was used as a negative control for Pex16p-mediated Pex3p recruitment. Reason: While PEX11A was not the focus of this paper, it was used as a peroxisomal membrane marker/control, and its localization to peroxisomes was confirmed by immunofluorescence. The peroxisome localization annotation is well-supported, though the more specific peroxisomal membrane (GO:0005778) term is preferable. Supporting Evidence: PMID:19114594 We confirmed the complementing activity of PEX14-EGFP, HA-PEX13, HA-PEX12, HA-PEX10, HA-PEX2, and PEX3-Myc, using respective PEX-defective mutants, and the peroxisome division activity of HA-PEX11alpha with wild-type CHO cells.
GO:0005777 peroxisome	IDA PMID:18782765 Targeting of hFis1 to peroxisomes is mediated by Pex19p.	ACCEPT	Summary: In Delille & Schrader (2008), Pex11p-alpha-YFP was used as a peroxisomal membrane marker in COS-7 cells to specifically label peroxisomes for subcellular fractionation experiments studying hFis1 targeting. The paper confirmed peroxisomal localization of Pex11p-alpha. Reason: PEX11A-YFP was explicitly shown to localize to peroxisomes by immunofluorescence. This is a well-supported localization annotation, though the more specific peroxisomal membrane (GO:0005778) is preferable. Supporting Evidence: PMID:18782765 Pex11pα-YFP, which exposes its N and C termini toward the cytosol ( 53 ), localized specifically to peroxisomes ( Fig PMID:18782765 In contrast to other peroxisomal membrane proteins (for example, Pex11pβ) ( 46 ), no morphological alterations of the peroxisomal compartment were induced by Pex11pα-YFP, which might have influenced the association of hFis1 ( Fig
GO:0005515 protein binding	IPI PMID:20826455 PEX11 family members are membrane elongation factors that co...	REMOVE	Summary: PEX11A was shown to interact with FIS1 (UniProtKB:Q9Y3D6) and PEX11G (UniProtKB:Q96HA9) by co-immunoprecipitation in Koch et al. (2010). However, 'protein binding' (GO:0005515) is too vague to be informative. The GOA file shows two separate IPI entries for this term, one for FIS1 and one for PEX11G. The interactions are functionally relevant: PEX11A-FIS1 interaction links membrane elongation to fission machinery recruitment, and PEX11A-PEX11G heterodimerization is part of the oligomerization required for function. Reason: Per curation guidelines, 'protein binding' (GO:0005515) is uninformative and should be avoided. The specific interactions with FIS1 and PEX11G are better captured by the homodimerization activity annotation (GO:0042803) and the protein-containing complex annotation (GO:0032991). The functional significance is already captured by the peroxisome fission annotation (GO:0016559). Supporting Evidence: PMID:20826455 We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1
GO:0005777 peroxisome	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	ACCEPT	Summary: Koch et al. (2010) showed PEX11A localizes to peroxisomes by fluorescence microscopy. This is the most comprehensive study of PEX11 family function. Reason: Peroxisome localization is core to PEX11A function and well-supported by this study. The more specific term peroxisomal membrane (GO:0005778) is also annotated separately. Supporting Evidence: PMID:20826455 Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs),which is evocative of an evolutionary conserved function of these proteins in membrane tubulation.
GO:0016559 peroxisome fission	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	ACCEPT	Summary: Koch et al. (2010) demonstrated that PEX11 family members (including PEX11A) are membrane elongation factors that coordinate peroxisome proliferation. Overexpression leads to juxtaposed elongated peroxisomes (JEPs), which represent intermediates in peroxisome division. Excess FIS1 can resolve JEPs into normal round peroxisomes, demonstrating the elongation-to-fission pathway. Reason: This is the key experimental paper establishing PEX11 proteins as membrane elongation factors coordinating peroxisome fission. The IDA evidence is strong and directly supports this core function annotation. Supporting Evidence: PMID:20826455 Our results demonstrate that PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression. PMID:20826455 We show that excess of hFis1 but not of DRP1 is sufficient to fragment JEPs into normal round-shaped organelles
GO:0032991 protein-containing complex	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	ACCEPT	Summary: Koch et al. (2010) demonstrated that PEX11A forms homodimers and heterodimers with PEX11G, and interacts with FIS1. The protein-containing complex annotation reflects these oligomerization properties. However, GO:0032991 is extremely generic. Reason: PEX11A demonstrably forms homo- and heterodimeric complexes (with PEX11G) and interacts with FIS1 as part of the fission machinery. While the term is generic, it accurately reflects the oligomeric nature of PEX11A. A more specific complex term would be preferable but none exists in GO for the PEX11 complex. Supporting Evidence: PMID:20826455 We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1
GO:0042803 protein homodimerization activity	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	ACCEPT	Summary: Koch et al. (2010) demonstrated PEX11A homodimerization by co-immunoprecipitation and showed that the C-terminal transmembrane domain (region 220-239) is required for homodimerization. Homodimerization is important for PEX11A membrane-shaping function. Reason: Homodimerization was directly demonstrated experimentally and is functionally important for PEX11A's membrane elongation activity. This is a well-supported molecular function annotation. UniProt also notes that region 220-239 is required for homodimerization. Supporting Evidence: PMID:20826455 We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1
GO:0044375 regulation of peroxisome size	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	ACCEPT	Summary: Koch et al. (2010) showed that overexpression of PEX11 family members leads to elongated peroxisomes (JEPs), directly demonstrating regulation of peroxisome morphology and size. This annotation captures the membrane remodeling aspect of PEX11A function. Reason: PEX11A overexpression leads to elongated peroxisomes, directly demonstrating its role in regulating peroxisome size/morphology. This complements the peroxisome fission annotation by capturing the upstream membrane remodeling step. Supporting Evidence: PMID:20826455 Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs),which is evocative of an evolutionary conserved function of these proteins in membrane tubulation.
GO:0005778 peroxisomal membrane	IDA PMID:9792670 Expression of PEX11beta mediates peroxisome proliferation in...	ACCEPT	Summary: Schrader et al. (1998) identified PEX11alpha and PEX11beta as novel human peroxisomal membrane proteins. PEX11alpha was characterized as a peroxisomal membrane protein whose expression is induced by peroxisome proliferators. Reason: This is one of the original papers characterizing PEX11A as a peroxisomal membrane protein. The peroxisomal membrane localization is directly demonstrated. Supporting Evidence: PMID:9792670 We report here the identification and characterization of two novel human peroxisomal membrane proteins, PEX11alpha and PEX11beta.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-1989753	ACCEPT	Summary: Reactome entry R-HSA-1989753 describes the expression of PEX11A as part of the PPARA activates gene expression pathway. The TAS annotation for peroxisomal membrane localization is consistent with all experimental evidence. Reason: The Reactome annotation correctly places PEX11A at the peroxisomal membrane. While the Reactome entry itself is minimal (just transcription/translation of PEX11A gene), the localization is well-established by multiple other sources. Supporting Evidence: PMID:9714566 PEX11 encoded a peroxisomal protein Pex11p comprising 247 amino acids, with two transmembrane segments and a dilysine motif at the C-terminus.
GO:0005778 peroxisomal membrane	IDA PMID:9714566 Clofibrate-inducible, 28-kDa peroxisomal integral membrane p...	ACCEPT	Summary: Abe et al. (1998) cloned human PEX11 cDNA and showed it encodes a 28 kDa peroxisomal integral membrane protein (PMP28) with two transmembrane segments. Topology studies showed both N- and C-terminal parts are exposed to the cytosol. The protein was shown to be the clofibrate-inducible PMP28 previously identified from rat liver. Reason: This is the original cloning and characterization paper for human PEX11A. It provides direct experimental evidence for peroxisomal membrane localization including topology mapping, co-migration with PMP28, and immunoreactivity with anti-PMP28 antibodies. Supporting Evidence: PMID:9714566 PEX11 encoded a peroxisomal protein Pex11p comprising 247 amino acids, with two transmembrane segments and a dilysine motif at the C-terminus. PMID:9714566 Pex11p exposes both N- and C-terminal parts to the cytosol.
GO:0007031 peroxisome organization	IMP PMID:9792670 Expression of PEX11beta mediates peroxisome proliferation in...	ACCEPT	Summary: Schrader et al. (1998) showed that overexpression of PEX11alpha induced peroxisome proliferation through a multistep process involving peroxisome elongation and division. PEX11alpha mRNA was induced more than 10-fold by peroxisome proliferators clofibrate and DEHP, suggesting a role in regulated peroxisome organization. Reason: The IMP evidence from overexpression studies directly shows PEX11A involvement in peroxisome organization. This is a parent term of peroxisome fission, and the annotation is well-supported by the observed peroxisome proliferation phenotype upon overexpression. Supporting Evidence: PMID:9792670 Overexpression of PEX11alpha also induced peroxisome proliferation but at a much lower frequency than PEX11beta in our experimental system. PMID:9792670 PEX11alpha mRNA levels varied widely among different tissues, were highest in tissues that are sensitive to peroxisome-proliferating agents, and were induced more than 10-fold in response to the peroxisome proliferators clofibrate and di(2-ethylhexyl) phthalate.
GO:0007165 signal transduction	IMP PMID:9792670 Expression of PEX11beta mediates peroxisome proliferation in...	REMOVE	Summary: This annotation to signal transduction (GO:0007165) is based on the observation that PEX11alpha is transcriptionally induced by peroxisome proliferators (clofibrate, DEHP) and that its mRNA levels are highest in tissues sensitive to these agents. However, PEX11A itself is not a signaling molecule -- it is a downstream effector of the PPARalpha signaling pathway. Being transcriptionally regulated by a signal does not make PEX11A "involved in" signal transduction. Reason: PEX11A is a target gene of PPARalpha-mediated signaling, not a component of the signal transduction machinery itself. The fact that PEX11A expression is induced by peroxisome proliferators reflects its regulation by the PPARalpha pathway, but PEX11A does not transduce signals. This is an over-annotation arising from conflating transcriptional response to a signal with participation in signal transduction. Signal transduction (GO:0007165) should be reserved for molecules that directly participate in signaling cascades (receptors, kinases, transcription factors, etc.), not their downstream structural/enzymatic targets. Supporting Evidence: PMID:9792670 PEX11alpha mRNA levels varied widely among different tissues, were highest in tissues that are sensitive to peroxisome-proliferating agents, and were induced more than 10-fold in response to the peroxisome proliferators clofibrate and di(2-ethylhexyl) phthalate.
GO:0005777 peroxisome	IDA PMID:9922452 Peroxisome synthesis in the absence of preexisting peroxisom...	ACCEPT	Summary: In South & Gould (1999), PEX11alpha-myc was expressed in PBD061 cells (PEX16-deficient) and control PBD094 cells as one of many PMPs tested for import. PEX11alpha-myc was used as a peroxisomal membrane protein marker. The paper is primarily about PEX16 and de novo peroxisome formation, not about PEX11A function. Reason: While PEX11A was not the focus of this study, it was used as a known peroxisomal membrane protein and its localization to peroxisomes was confirmed. The annotation is correct. Supporting Evidence: PMID:9922452 Similar results were observed in cells transfected with expression vectors designed to express other human PMPs, including PEX3myc (Kammerer et al., 1998), PEX10myc (Warren et al., 1998), PEX11αmyc (Schrader et al., 1998), PEX11βmyc (Schrader et al., 1998), and PEX13myc (Gould et al., 1996) (data not shown)
GO:0046982 protein heterodimerization activity	IDA PMID:20826455 PEX11 family members are membrane elongation factors that co...	NEW	Summary: Koch et al. (2010) demonstrated that PEX11A forms heterodimers with PEX11G in addition to homodimers. This heterodimerization activity is functionally significant for coordinating peroxisome proliferation. The homodimerization activity is already annotated (GO:0042803) but the heterodimerization with PEX11G is not captured. Reason: PEX11A-PEX11G heterodimerization was directly demonstrated by Koch et al. (2010) and is an important aspect of PEX11A molecular function not currently captured by existing annotations. UniProt also states PEX11A is a heterodimer with PEX11G. Supporting Evidence: PMID:20826455 We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1

Gene Description

Existing Annotations Review

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